| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma [NCT01169337] | Phase 3 | 226 participants (Actual) | Interventional | 2011-01-24 | Active, not recruiting |
| A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leuke [NCT01522976] | Phase 2 | 282 participants (Actual) | Interventional | 2012-03-01 | Active, not recruiting |
| A Phase 1b Study of PVX-410, a Multi-Peptide Cancer Vaccine, and Citarinostat (CC-96241), a Histone Deacetylase Inhibitor (HDAC) With and Without Lenalidomide for Patients With Smoldering Multiple Myeloma [NCT02886065] | Phase 1 | 19 participants (Actual) | Interventional | 2017-03-07 | Active, not recruiting |
| Pilot-trial of Methotrexate, Tafasitamab (Minjuvi®), Lenalidomide (Revlimid®) and Rituximab in Patients Ineligible for HCT-ASCT With Primary Central Nervous System Lymphoma (PCNSL) [NCT05583071] | Phase 2 | 20 participants (Anticipated) | Interventional | 2023-05-31 | Not yet recruiting |
| Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia [NCT01132586] | Phase 1 | 61 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies [NCT01254578] | Phase 1 | 17 participants (Actual) | Interventional | 2010-11-24 | Completed |
| A Phase II Study of the Bruton's Tyrosine Kinase Inhibitor, Zanubrutinib, in Combination With Lenalidomide Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma [NCT05200312] | Phase 2 | 36 participants (Anticipated) | Interventional | 2022-02-01 | Recruiting |
| A Multicenter, Randomized, Parallel-Group, Double-blind, Placebo-controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma [NCT00056160] | Phase 3 | 353 participants (Actual) | Interventional | 2003-01-01 | Completed |
| CLLM1-Protocol of the German CLL-Study Group (GCLLSG) A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) as Maintenance Therapy for High-risk Patients With Chro [NCT01556776] | Phase 3 | 89 participants (Actual) | Interventional | 2012-07-20 | Completed |
| A Phase 1 and Phase 2 Study of Lenalidomide (Revlimid) in Combination With Cyclophosphamide (Endoxan) and Prednison (REP) in Relapsed/Refractory Multiple Myeloma [NCT01352338] | Phase 1/Phase 2 | 82 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of iR2 (Ibrutinib，Lenalidomide, Rituximab）in Untreated and Unfit Elderly Patients With Diffuse Large B-cell Lymphoma [NCT03949062] | Phase 2 | 30 participants (Actual) | Interventional | 2019-03-13 | Active, not recruiting |
| A Phase III, Open-Label, Multicenter Randomized Study Evaluating Glofitamab as a Single Agent Versus Investigator's Choice in Patients With Relapsed/Refractory Mantle Cell Lymphoma [NCT06084936] | Phase 3 | 182 participants (Anticipated) | Interventional | 2023-10-22 | Recruiting |
| A Phase II Study of Selinexor In Addition to Lenalidomide for Consolidation and Maintenance Treatment After Autologous Hematopoietic Cell Transplant in Multiple Myeloma [NCT05820763] | Phase 2 | 35 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| A Randomized, Controlled, Open-label, Multicenter, Inferentially Seamless Phase 2/3 Study of Ibrutinib in Combination With Rituximab Versus Physician's Choice of Lenalidomide Plus Rituximab or Bortezomib Plus Rituximab in Participants With Relapsed or Ref [NCT05564052] | Phase 2 | 36 participants (Actual) | Interventional | 2022-12-06 | Active, not recruiting |
| A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab SC and Lenalidomide (Tal-DR) Versus Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) in Part [NCT05552222] | Phase 3 | 1,590 participants (Anticipated) | Interventional | 2022-10-25 | Recruiting |
| A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study [NCT05438043] | Phase 3 | 500 participants (Anticipated) | Interventional | 2022-12-15 | Recruiting |
| Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma [NCT05137054] | Phase 1 | 317 participants (Anticipated) | Interventional | 2022-08-17 | Recruiting |
| A Multi-arm Phase 1b Study of Talquetamab With Other Anticancer Therapies in Participants With Multiple Myeloma [NCT05050097] | Phase 1 | 182 participants (Anticipated) | Interventional | 2021-09-22 | Recruiting |
| A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) [NCT04923893] | Phase 3 | 650 participants (Anticipated) | Interventional | 2021-08-19 | Recruiting |
| A Multi-arm Phase 1b Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma [NCT04722146] | Phase 1 | 140 participants (Actual) | Interventional | 2021-03-12 | Active, not recruiting |
| Phase I Trial of Methotrexate, Rituximab, Lenalidomide, and Nivolumab (Nivo-MR2) Induction Followed by Lenalidomide and Nivolumab Maintenance in Primary CNS Lymphoma [NCT04609046] | Phase 1 | 32 participants (Anticipated) | Interventional | 2021-05-24 | Recruiting |
| A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma [NCT04133636] | Phase 2 | 169 participants (Actual) | Interventional | 2019-11-07 | Active, not recruiting |
| A Randomized Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant [NCT03901963] | Phase 3 | 200 participants (Actual) | Interventional | 2019-04-26 | Active, not recruiting |
| A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Pla [NCT03652064] | Phase 3 | 395 participants (Actual) | Interventional | 2018-11-06 | Active, not recruiting |
| An Open-Label, Single Arm, Phase 2a Study of Bortezomib, Lenalidomide, Dexamethasone and Elotuzumab in Newly Diagnosed Multiple Myeloma [NCT02375555] | Phase 2 | 40 participants (Actual) | Interventional | 2015-05-07 | Active, not recruiting |
| A Phase 1 Study of Lenalidomide and Ibrutinib in Combination With Rituximab in Relapsed and Refractory CLL and SLL [NCT02160015] | Phase 1 | 12 participants (Actual) | Interventional | 2014-05-20 | Active, not recruiting |
| A Phase II Study of Lenalidomide (CC-5013) in Combination With Prednisone for the Treatment of Myelofibrosis With Myeloid Metaplasia [NCT00227591] | Phase 2 | 48 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Elotuzumab in Combination With Carfilzomib, Lenalidomide and Dexamethasone (E-KRd) Versus KRd Prior to and Following Auto-SCT in Newly Diagnosed Multipe Myeloma and Subsequent Maintenance With Elotuzumab and Lenalidomide Versus Single-Agent Lenalidomide- [NCT03948035] | Phase 3 | 576 participants (Anticipated) | Interventional | 2018-08-28 | Active, not recruiting |
| KRd Consolidation in Myeloma Patients With a Positive PET-CT After Standard First Line Treatment. A Phase II Study [NCT03314636] | Phase 2 | 53 participants (Actual) | Interventional | 2018-03-16 | Active, not recruiting |
| Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR) [NCT02765854] | Phase 2 | 72 participants (Actual) | Interventional | 2016-09-01 | Active, not recruiting |
| A Phase II Study of MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia(CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL), Including Those Who Have Relapsed on Ibrutinib, or Pat [NCT02005289] | Phase 2 | 41 participants (Actual) | Interventional | 2014-01-17 | Active, not recruiting |
| Assessment of Bortezomib (Alvocade ®) Efficacy and Safety in Newly Diagnosed Multiple Myeloma Patients [NCT04348006] | Phase 4 | 0 participants (Actual) | Interventional | 2020-03-01 | Withdrawn(stopped due to No patients were enrolled in the study) |
| A Randomized, Open-label Phase 3 Study of Carfilzomib, Lenalidomide, and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone (KRd vs. VRd) in Patients With Newly Diagnosed Multiple Myeloma (COBRA) [NCT03729804] | Phase 3 | 250 participants (Anticipated) | Interventional | 2019-05-07 | Recruiting |
| Open-label, Single-arm, Phase 2 Study of Initial Treatment With Daratumumab (Darzalex), Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy [NCT03500445] | Phase 2 | 75 participants (Anticipated) | Interventional | 2019-02-13 | Recruiting |
| Open-label, Single-arm, Phase 2 Study of Initial Treatment With Elotuzumab, Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (E-KRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy [NCT02969837] | Phase 2 | 47 participants (Actual) | Interventional | 2017-07-10 | Active, not recruiting |
| Phase 3 Randomized Trial of Carfilzomib, Lenalidomide, Dexamethasone Versus Lenalidomide Alone After Stem-cell Transplant for Multiple Myeloma [NCT02659293] | Phase 3 | 180 participants (Actual) | Interventional | 2016-04-26 | Active, not recruiting |
| Phase II Randomized Trial of Continuation of Post-Transplant Maintenance With Single-Agent Lenalidomide vs. Consolidation/Maintenance With Ixazomib-Lenalidomide-Dexamethasone in Patients With Residual Myeloma [NCT02389517] | Phase 2 | 42 participants (Actual) | Interventional | 2015-03-02 | Active, not recruiting |
| Prospective, Multi-center Phase I/II Trial of Lenalidomide and Dose-Adjusted EPOCH-R in MYC-Associated B-Cell Lymphomas [NCT02213913] | Phase 1/Phase 2 | 46 participants (Anticipated) | Interventional | 2014-07-29 | Active, not recruiting |
| A Phase I, Multicenter, Open-label, Dose-escalation Study to Assess the Safety of Lenalidomide in Patients With Advanced Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphoma [NCT01169298] | Phase 1 | 13 participants (Actual) | Interventional | 2010-07-01 | Completed |
| Pilot Study Immunomonitoring NK Cells in Patients With Myeloid Malignancies [NCT02525250] | | 14 participants (Actual) | Interventional | 2012-12-31 | Completed |
| Randomized Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone to High-Dose Treatment With ASCT in the Initial Management of Myeloma in Patients up to 65 Years of Age [NCT01191060] | Phase 3 | 700 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Phase II Multicentric Trial Maintenance Therapy With 6 Monthly Revlimid® Cycles Alternated With 6 Monthly Vidaza® Cycles in First CR After Induction LIA Chemotherapy for Elderly Fit Patients With Poor Prognosis Acute Myeloid Leukemia. [NCT01301820] | Phase 2 | 120 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase 2, Multicenter, Single Arm, Open Label Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy [NCT03785184] | Phase 2 | 0 participants (Actual) | Interventional | 2019-04-29 | Withdrawn(stopped due to Strategic considerations) |
| Pilot Study of GC. (Gemcitabine-Rituximab-Oxaliplatin Combination) Given Every 14 Days With Maintenance Lenalidomide for the Treatment of Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma [NCT01307592] | Phase 2 | 70 participants (Anticipated) | Interventional | 2011-02-28 | Recruiting |
| GEM-CLARIDEX: Lenalidomide and Dexamethasone (Ld) Versus Clarithromycin / Lenalidomide [Revlimid®] / Dexamethasone (BiRd) as Initial Therapy in Multiple Myeloma [NCT02575144] | Phase 3 | 286 participants (Actual) | Interventional | 2015-09-30 | Active, not recruiting |
| Phase II Study of Lenalidomide Maintenance After Salvage Therapy in Patients With Relapsed and/or Refractory Non-Hodgkin T-cell Lymphoma [NCT03730740] | Phase 2 | 79 participants (Anticipated) | Interventional | 2018-11-16 | Recruiting |
| A Phase 1b, Dose Escalation Study to Determine the Recommended Phase 2 Dose of TAK-659 in Combination With Bendamustine (±Rituximab), Gemcitabine, Lenalidomide, or Ibrutinib for the Treatment of Patients With Advanced Non-Hodgkin Lymphoma After At Least 1 [NCT02954406] | Phase 1 | 43 participants (Actual) | Interventional | 2017-03-05 | Terminated(stopped due to Business decision, insufficient enrollment, no safety or efficacy concerns.) |
| Phase II Trial Studying the Efficacy of a Triplet Combination of MLN9708, Lenalidomide and Dexamethasone as Induction Prior to, and as Consolidation After High-dose Therapy With Peripheral Stem Cell Transplantation Followed by MLN9708 Maintenance in the I [NCT01936532] | Phase 2 | 42 participants (Actual) | Interventional | 2014-11-12 | Completed |
| Open-label Phase 2 Pilot Study of Lenalidomide (Revlimid) as Adjuvant Treatment for Refractory Cutaneous T Cell Lymphoma [NCT01132989] | Phase 2 | 10 participants (Anticipated) | Interventional | 2010-05-31 | Recruiting |
| Chindamide in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma, a Phase II Trial [NCT03605056] | Phase 2 | 25 participants (Anticipated) | Interventional | 2018-07-31 | Not yet recruiting |
| A Phase 2, Multicenter, Randomized, Open-label, Parallel-group Study of a Lenalidomide (Revlimid®) Regimen or a Sequential Azacitidine (Vidaza®) Plus Lenalidomide (Revlimid®) Regimen Versus an Azacitidine (Vidaza®) Regimen for Therapy of Older Subjects Wi [NCT01358734] | Phase 2 | 88 participants (Actual) | Interventional | 2012-04-27 | Completed |
| A Phase 1/2, Open-Label, Multicenter Study of ACY-1215 (Ricolinostat) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma [NCT01583283] | Phase 1 | 38 participants (Actual) | Interventional | 2012-07-12 | Completed |
| Multicenter, Open Label, Phase II Trial to Evaluate the Efficacy and Safety of Treatment With Lenalidomide in Kaposi Disease Associated With HIV Infection (ANRS 154/LENAKAP) [NCT01282047] | Phase 2 | 12 participants (Actual) | Interventional | 2011-10-31 | Terminated |
| A Phase 1, Open-label, Multicenter Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (KarMMa-4) [NCT04196491] | Phase 1 | 13 participants (Actual) | Interventional | 2020-05-27 | Completed |
| Lenalidomide Therapy In Previously Untreated, Advanced Stage Follicular Lymphoma [NCT01180569] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2010-08-31 | Withdrawn |
| A Phase I Open-label Dose-escalation Study With Lenalidomide in Combination With a Fixed Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma [NCT01348503] | Phase 1 | 5 participants (Actual) | Interventional | 2011-05-31 | Terminated(stopped due to Treatment was ineffective) |
| A Multicenter Open-Label Phase 1b/2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [NCT02077166] | Phase 1/Phase 2 | 138 participants (Actual) | Interventional | 2014-03-13 | Completed |
| Phase 1, Multicenter, Open-label, Dose-escalation Study of Sotatercept (ACE-011) in Combination With Lenalidomide or Pomalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01562405] | Phase 1 | 33 participants (Actual) | Interventional | 2012-05-31 | Active, not recruiting |
| R2 in the Treatment of Follicular Lymphoma Grade 1-3A [NCT03715309] | Phase 2 | 115 participants (Anticipated) | Interventional | 2018-11-01 | Recruiting |
| A Phase 1b, Open-label, Multicenter Study of (BMS-936564) in Combination With Lenalidomide (Revlimid) Plus Low-dose Dexamethasone, or With Bortezomib (Velcade) Plus Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma [NCT01359657] | Phase 1 | 46 participants (Actual) | Interventional | 2011-09-30 | Completed |
| University of Arkansas (UARK# 2017-03): A Single-Arm, Open-label Study of Anti-SLAMF7 mAb Therapy After Autologous Stem Cell Transplant in Patients With Multiple Myeloma (Total Therapy 8) [NCT03168100] | Phase 2 | 0 participants (Actual) | Interventional | 2017-10-01 | Withdrawn(stopped due to No study population. No subjects enrolled.) |
| A Platform Study Evaluating the Safety and Efficacy of Multiple Treatments in Patients With Multiple Myeloma [NCT05583617] | Phase 1/Phase 2 | 200 participants (Anticipated) | Interventional | 2023-11-14 | Recruiting |
| Myeloma XIV: A Phase III Trial to Compare Standard and Frailty-adjusted Induction Therapy With Ixazomib, Lenalidomide and Dexamethasone (IRD) and Maintenance Lenalidomide (R) to Lenalidomide Plus Ixazomib (R+I) [NCT03720041] | Phase 3 | 740 participants (Anticipated) | Interventional | 2020-08-04 | Recruiting |
| A Prospective Trial of Revlimid® in Transfusion Dependent Patients With Non-del (5q) Low/Intermediate-1 Risk Myelodysplastic Syndrome [NCT01178814] | Phase 2 | 57 participants (Actual) | Interventional | 2010-07-31 | Active, not recruiting |
| LCCC 1111: An Open-Label Dose-Finding Study of Lenalidomide as Reinduction/ Consolidation Followed by Lenalidomide Maintenance Therapy for Adults ≥ 60 Years of Age With Acute Myeloid Leukemia (AML) in Partial or Complete Response Following Conventional In [NCT01578954] | Phase 1 | 20 participants (Actual) | Interventional | 2012-06-28 | Completed |
| Phase I/II Study of the Combination of 5-azacitidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML) [NCT01038635] | Phase 1/Phase 2 | 94 participants (Actual) | Interventional | 2009-12-31 | Completed |
| A Randomised Phase II Study Comparing LEnalidomide Plus Rituximab, GEmcitabine and Methylprednisolone (LR-GEM) to Rituximab, Gemcitabine, Methylprednisolone and cisplatiN (R-GEM-P) in Second-line Treatment of Diffuse Large B-cell Lymphoma (DLBCL). [NCT02060656] | Phase 2 | 92 participants (Anticipated) | Interventional | 2013-09-30 | Active, not recruiting |
| Combined Intravitreal Methotrexate and R2 Regimen Followed by Lenalidomide Maintenance in Newly-diagnosed Primary Vitreoretinal Lymphoma [NCT03746223] | Phase 2 | 42 participants (Anticipated) | Interventional | 2018-11-15 | Recruiting |
| A Phase I Trial of Lenalidomide and Radiotherapy in Children With Diffuse Intrinsic Pontine Gliomas and High-grade Gliomas [NCT01222754] | Phase 1 | 29 participants (Actual) | Interventional | 2010-11-23 | Completed |
| A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of the Efficacy and Safety of 2 Doses of Lenalidomide Versus Placebo in Red Blood Cell (RBC) Transfusion-Dependent Subjects With Low- or Intermediate-1-Risk Myelodysplastic Syndromes [NCT00179621] | Phase 3 | 205 participants (Actual) | Interventional | 2005-07-31 | Completed |
| A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab in Combination With Daratumumab, Lenalidomide, and Dexamethasone With or Without Bortezomib as Induction Therapy and Teclistamab in Combination With Daratumumab and Lenalidomide as Maintenance [NCT05695508] | Phase 2 | 70 participants (Anticipated) | Interventional | 2022-12-01 | Recruiting |
| Phase II Trial for Newly Diagnosed Low-risk Multiple Myeloma Patients Comparing 6 Cycles of Isatuximab With Lenalidomide/Bortezomib/Dexamethasone (I-VRD) Compared to 3 Cycles of I-VRD Followed by One Cycle of High-dose Therapy and Both Arms Followed by Ma [NCT05665140] | Phase 2/Phase 3 | 100 participants (Anticipated) | Interventional | 2023-02-03 | Recruiting |
| Randomized Phase II Open Label Study of Lenalidomide R-CHOP (R2CHOP) vs. RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) in Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma [NCT01856192] | Phase 2 | 349 participants (Actual) | Interventional | 2013-08-27 | Active, not recruiting |
| A Phase II Randomized Trial of Lenalidomide (NSC # 703813) in Pediatric Patients With Recurrent, Refractory or Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas [NCT01553149] | Phase 2 | 75 participants (Actual) | Interventional | 2012-03-19 | Active, not recruiting |
| Clinical Study on the Efficacy and Safety of Anti-PD-1 Monoclonal Antibody Combined Lenalidomide and Azacitidine in Relapsed/Refractory Peripheral T-cell Lymphoma [NCT05182957] | Phase 2 | 40 participants (Anticipated) | Interventional | 2022-12-14 | Recruiting |
| Safety, Tolerability, and Efficacy of Once Weekly Carfilzomib in Combination With Daratumumab, Lenalidomide and Dexamethasone, in Transplant-ineligible Multiple Myeloma Patients Non-responsive to a Bortezomib Based Induction [NCT04065789] | Phase 2 | 41 participants (Actual) | Interventional | 2018-05-02 | Completed |
| A Phase I/II Study of Lenalidomide in Patients With Chronic Myelomonocytic Leukemia [NCT01368757] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2010-06-30 | Active, not recruiting |
| Phase I Study of Everolimus (RAD001) in Combination With Lenalidomide in Patients With Advanced Solid Malignancies Enriched for Renal Cell Carcinoma [NCT01218555] | Phase 1 | 44 participants (Actual) | Interventional | 2010-09-09 | Completed |
| Post-marketing Phase 4 Study to Evaluate Safety, Tolerability, and Efficacy of Kyprolis® (Carfilzomib) in Indian Patients With Relapsed or Refractory Multiple Myeloma: A Prospective, Open-label, Non-comparative, Multicenter Study [NCT03934684] | Phase 4 | 100 participants (Anticipated) | Interventional | 2019-09-16 | Active, not recruiting |
| A Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1 [NCT00109772] | Phase 2 | 184 participants (Actual) | Interventional | 2005-02-28 | Terminated(stopped due to Interim analysis showed the primary outcome was not reached) |
| A Phase I/II Study of the Combination of Pembrolizumab and Lenalidomide, in Patients With Relapsed Non-Hodgkin and Hodgkin Lymphoma [NCT02875067] | Phase 1/Phase 2 | 6 participants (Actual) | Interventional | 2016-08-29 | Terminated(stopped due to Merck's decision for early termination of the data) |
| A Phase III Study Comparing Lenalidomide and Subcutaneous Daratumumab (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy [NCT03993912] | Phase 3 | 294 participants (Anticipated) | Interventional | 2019-10-17 | Active, not recruiting |
| Phase 3b, Randomized Trial of Continuous Revlimid® (Lenalidomide) Therapy Versus Observation Following Induction Therapy That Does Not Include Revlimid, Pomalyst® or Thalomid® in Newly Diagnosed Multiple Myeloma [NCT02155634] | Phase 3 | 0 participants (Actual) | Interventional | 2014-07-31 | Withdrawn(stopped due to The study was terminated due to poor feasibility and lack of interest at the participating sites.) |
| Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML) [NCT02255162] | Phase 1 | 8 participants (Actual) | Interventional | 2015-01-31 | Terminated(stopped due to Slow Accrual) |
| "A Prospective Non-interventional Post-authorization Safety Study (PASS) of Lenalidomide in Previously Untreated Adult Multiple Myeloma Patients Who Are Not Eligible for Transplant (Transplant Noneligible [TNE])" [NCT03106324] | | 911 participants (Actual) | Observational [Patient Registry] | 2017-03-31 | Active, not recruiting |
| Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia [NCT01185262] | Phase 1 | 25 participants (Actual) | Interventional | 2009-04-30 | Completed |
| PILOT STUDY PHASE II, Multicenter, Non-randomized, TO ASSESS THE EFFICACY AND SAFETY OF LENALIDOMIDE IN INDUCTION AND POST-INDUCTION IN PATIENTS WITH NOVO Acute Myeloid Leukemia (AML) WITH Cytogenetic Abnormality Monosomy 5 [NCT01198054] | Phase 4 | 4 participants (Actual) | Interventional | 2011-01-31 | Terminated |
| A Phase I Study of Epigenetic Immunomodulation Through the Use of Azacitidine, Lenalidomide, and Grifola Frondosa in Patients With Advanced Malignancy [NCT01200004] | Phase 1 | 1 participants (Actual) | Interventional | 2012-04-30 | Terminated(stopped due to Slow Accrual.) |
| Phase IB Study of Lenalidomide (Revlimid®) With Liposomal Doxorubicin (Doxil®) and Bevacizumab (Avastin®) for Patients With Platinum Resistant Ovarian Cancer. [NCT01202890] | Phase 1 | 1 participants (Actual) | Interventional | 2010-09-30 | Terminated(stopped due to Terminated due to inadequate rate of accrual.) |
| CC-5013 Alone or in Combination With Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) [NCT00096044] | Phase 2 | 45 participants (Actual) | Interventional | 2004-03-31 | Completed |
| A Multicenter, Single-arm, Open-label Phase II Study of the Safety of Lenalidomide Monotherapy and Markers for Disease Progression in Patients With IPSS Low- or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Associated With an Isolated Deletion 5q Cy [NCT01081431] | Phase 2 | 91 participants (Actual) | Interventional | 2010-03-31 | Active, not recruiting |
| A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Azacitidine in Intermediate-2 or High Risk MDS With Del 5q [NCT01088373] | Phase 2 | 50 participants (Actual) | Interventional | 2010-03-25 | Completed |
| A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Clinical Activity of Durvalumab in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) or With Lenalidomide Plus R-CHOP (R2-CHOP) in Subjects With [NCT03003520] | Phase 2 | 46 participants (Actual) | Interventional | 2017-02-28 | Completed |
| Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation - MajesTEC-4 [NCT05243797] | Phase 3 | 1,572 participants (Anticipated) | Interventional | 2022-09-08 | Recruiting |
| Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly-Diagnosed Multiple Myeloma: A Clinical and Correlative Phase II Study [NCT03290950] | Phase 2 | 75 participants (Actual) | Interventional | 2017-09-25 | Active, not recruiting |
| A Multicenter, Single-arm, Open-label Study of the Efficacy and Safety of Lenalidomide Monotherapy in Red Blood Cell Transfusion-dependent Subjects With Myelodysplastic Syndromes Associated With a Del(5q) Cytogenetic Abnormality. [NCT00065156] | Phase 2 | 148 participants (Actual) | Interventional | 2003-06-01 | Completed |
| A Phase III Study of Lenalidomide Maintenance After Debulking Therapy in Patients With Advanced Cutaneous T-Cell Lymphoma [NCT01098656] | Phase 3 | 21 participants (Actual) | Interventional | 2010-07-31 | Terminated(stopped due to recruitment prematurely halted following company's decision to stop financial support to the study) |
| Am Open-Label Phase II Study of the Safety and Efficacy of Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma [NCT00378209] | Phase 2 | 65 participants (Actual) | Interventional | 2006-08-31 | Completed |
| An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome [NCT03416374] | Phase 4 | 45 participants (Actual) | Interventional | 2018-02-18 | Completed |
| A Phase I Study of Lenalidomide in Combination With Decitabine for Patients With High Grade Myelodysplastic Syndromes [NCT00828802] | Phase 1 | 15 participants (Actual) | Interventional | 2009-03-31 | Completed |
| A Randomized Phase III Multicenter Trial Assessing Efficacy and Toxicity of a Combination of Rituximab and Lenalidomide (R2) vs Rituximab Alone as Maintenance After Chemoimmunotherapy With Rituximab-chemotherapy (R-CHT) for Relapsed/Refractory FL Patients [NCT02390869] | Phase 3 | 128 participants (Actual) | Interventional | 2014-05-31 | Active, not recruiting |
| A Phase I/II Clinical Trial of Lenalidomide in Combination With Oral Cyclophosphamide in Patients With Previously Treated Hormone Refractory Prostate Cancer [NCT01093183] | Phase 1/Phase 2 | 25 participants (Actual) | Interventional | 2010-03-04 | Terminated(stopped due to study sponsors withdrew support for the study drug.) |
| A Phase 1/2 Study of Ixazomib as a Replacement for Bortezomib or Carfilzomib for Multiple Myeloma (MM) Patients Recently Relapsed or Refractory to Their Last Combination Regimen Containing Either Bortezomib or Carfilzomib [NCT02206425] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2014-09-30 | Completed |
| A PHASE II, MULTI-CENTER, OPEN LABEL STUDY OF CYCLOPHOSPHAMIDE IN MULTIPLE MYELOMA PATIENTS WITH BIOCHEMICAL PROGRESSION DURING LENALIDOMIDE-DEXAMETHASONE TREATMENT FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA [NCT02206503] | Phase 2 | 13 participants (Actual) | Interventional | 2013-03-31 | Completed |
| A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702) [NCT01109004] | Phase 3 | 758 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Study Comparing the Efficacy and Safety of Genotype-guided R-CHOP-X Versus R-CHOP in Patients With Diffuse Large B-Cell Lymphoma [NCT05351346] | Phase 3 | 1,100 participants (Anticipated) | Interventional | 2022-06-01 | Recruiting |
| Isatuximab in Combination With Lenalidomide-Dexamethasone Compared to Lenalidomide-Dexamethasone in Elderly Patients (Aged ≥70 Years) With Newly Diagnosed Myeloma: a Randomized Phase II Study (SGZ-2019-12650) [NCT04891809] | Phase 2 | 198 participants (Anticipated) | Interventional | 2021-10-20 | Recruiting |
| A Randomized, Phase II Trial Evaluating the Efficacy and Safety of Lenalidomide, Bortezomib and Dexamethasone (RVD) With or Without Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma [NCT02720510] | Phase 2 | 6 participants (Actual) | Interventional | 2016-06-14 | Terminated(stopped due to A study was terminated due to low enrollment.) |
| A Multicenter, Phase 1/2 Study of Selinexor in Combination With Backbone Treatments or Novel Therapies in Patients With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL) [NCT04607772] | Phase 1/Phase 2 | 350 participants (Anticipated) | Interventional | 2020-11-18 | Suspended(stopped due to Sponsor decision) |
| Phase II, Single-arm Trial of Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT [NCT05497102] | Phase 2 | 58 participants (Anticipated) | Interventional | 2021-11-08 | Recruiting |
| Real-world Evidence of Carfilzomib, Lenalidomide, Dexamethasone Combination Therapy in Korean Relapsed and/or Refractory Multiple Myeloma Patients [NCT05495620] | | 300 participants (Anticipated) | Observational | 2022-08-01 | Not yet recruiting |
| Phase 1 Study of Lenalidomide/Dexamethasone With Nivolumab and Ipilimumab in Patients With Newly Diagnosed Multiple Myeloma [NCT03283046] | Phase 1 | 0 participants (Actual) | Interventional | 2017-10-31 | Withdrawn(stopped due to Similar to another study.) |
| Clinical Phase II, Multicenter, Open-label Study Evaluating iNduction, Consolidation and Maintenance With Isatuximab (SAR650984), Carfilzomib, LEnalidomide and Dexamethasone (I-KRd) in Primary Diagnosed High-risk Multiple Myeloma paTients [NCT03104842] | Phase 2 | 246 participants (Actual) | Interventional | 2017-08-15 | Active, not recruiting |
| A Phase Ib Study of the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Patients With Multiple Myeloma (Relapsed/Refractory and Post-Autologous Stem Cell Transpl [NCT02431208] | Phase 1 | 85 participants (Actual) | Interventional | 2015-07-22 | Completed |
| "Monoclonal Antibodies for Treatment of Multiple Myeloma. Present Status and Aspects of Effector Mechanisms With Emphasis on the CD38 Antibody Daratumumab " [NCT02419118] | Phase 2/Phase 3 | 4 participants (Actual) | Interventional | 2015-01-31 | Completed |
| A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01564537] | Phase 3 | 722 participants (Actual) | Interventional | 2012-08-01 | Completed |
| A Phase I Trial of B-cell Maturation Antigen (BCMA) Targeted EGFRt/BCMA-41BBz Chimeric Antigen Receptor (CAR) Modified T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma (MM) [NCT03070327] | Phase 1 | 20 participants (Actual) | Interventional | 2017-02-27 | Active, not recruiting |
| Toward a Risk-adapted Strategy to Cure Myeloma : An Intensive Program With Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab as Extended Induction and Consolidation Followed by Lenalidomide Maintenance in Newly Diagnosed Standard Risk Multiple My [NCT03669445] | Phase 2 | 45 participants (Anticipated) | Interventional | 2018-12-31 | Recruiting |
| Immune Modulation by Addition of Oral Lenalidomide to Intravesical BCG (Bacille Calmette-Guerrin) for Therapy of Non-muscle-invasive Transitional Cell Bladder Cancer [NCT01373294] | Phase 2 | 17 participants (Actual) | Interventional | 2011-11-30 | Completed |
| Prospective, Single-center, Single-arm, Open-label Study of Obinutuzumab, Zanubrutinib and Lenalidomide Sequential CD19/CD22 CAR-T in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma [NCT05797948] | | 20 participants (Anticipated) | Interventional | 2022-07-01 | Enrolling by invitation |
| A Multicenter, Open-label, Prospective Study of Ixazomib, Lenalidomide, and Ixazomib in Combination With Lenalidomide for Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma [NCT04217967] | Phase 4 | 180 participants (Anticipated) | Interventional | 2020-01-03 | Recruiting |
| A Phase IB/II Trial of Lenalidomide (Revlimid®), Ixazomib and Rituximab (RIXAR) as Front-line Therapy for High Risk Indolent B Cell Lymphoma [NCT02898259] | Phase 1/Phase 2 | 19 participants (Actual) | Interventional | 2017-02-20 | Terminated(stopped due to Funding was eliminated.) |
| [NCT01036399] | Phase 2 | 9 participants (Actual) | Interventional | 2008-11-30 | Terminated(stopped due to The EC withdrawn the approval becuase of possible conflicts of interests between our Institute and Supporter (Celgene)) |
| Phase 1 Clinical Trial to Evaluate Security and Dose of Expanded and Activated Autologous NK Cells Infusions in Consolidation of Multiple Myeloma Patients Treatment on Second or Later Relapse. [NCT02481934] | Phase 1 | 5 participants (Actual) | Interventional | 2013-03-31 | Completed |
| A Multi-center, Open-label Extended Access Program of Lenalidomide Plus Low-dose Dexamethasone in Chinese Subjects With Relapsed/Refactory Multiple Myeloma Who Participated in Study CC-5013-MM-021 for at Least One Year. [NCT02348528] | Phase 2 | 65 participants (Actual) | Interventional | 2012-09-11 | Completed |
| A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas [NCT03373305] | Phase 1 | 0 participants (Actual) | Interventional | 2019-03-31 | Withdrawn(stopped due to contract not executed) |
| An Open-Label, Multicenter Phase 1b Study Investigating the Safety of TAK-079 in Combination With Backbone Regimens for the Treatment of Patients With Newly Diagnosed Multiple Myeloma and for Whom Stem Cell Transplantation Is Not Planned as Initial Therap [NCT03984097] | Phase 1 | 50 participants (Actual) | Interventional | 2019-07-29 | Active, not recruiting |
| Single Arm Open-label Trial to Investigate the Efficacy and Safety of Lenlidomide as a Treatment for Recurrent or Refractory Crow-Fukase (POEMS) Syndrome [NCT02193698] | Phase 2 | 5 participants (Actual) | Interventional | 2014-07-31 | Completed |
| A Phase 2, Open-Label, Multicenter Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Patients With Relapsed and/or Refractory Multiple Myeloma [NCT02917941] | Phase 2 | 34 participants (Actual) | Interventional | 2016-11-01 | Completed |
| Phase I Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose And To Evaluate The Safety Profile of Lenalidomide (Revlimid® CC-5013) With Every Three Week Docetaxel (Taxotere®) In Subjects With Androgen Independent Prostate Cancer [NCT01378091] | Phase 1 | 64 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Combination of Rituximab, Lenalidomide and Nivolumab for Relapsed/ Refractory Non-germinal Center (Non-GCB) Type Diffuse Large B Cell Lymphoma (DLBCL) Including Primary Central Nervous System Lymphoma (PCNSL): A Phase 1/2 Trial [NCT03558750] | Phase 1 | 6 participants (Actual) | Interventional | 2018-06-14 | Terminated(stopped due to Low accrual) |
| Pilot Clinical Study of DNA Vaccination Against Neuroblastoma [NCT04049864] | Early Phase 1 | 12 participants (Anticipated) | Interventional | 2019-01-09 | Recruiting |
| Phase II Trial of Daratumumab for Transplant-Eligible Multiple Myeloma Patients [NCT03477539] | Phase 2 | 50 participants (Actual) | Interventional | 2018-04-09 | Active, not recruiting |
| Phase II Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects With Relapsed Follicular Lymphoma [NCT02446457] | Phase 2 | 53 participants (Actual) | Interventional | 2015-07-31 | Active, not recruiting |
| Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Untreated CLL/SLL The HiLOG Trial [NCT01496976] | Phase 2 | 45 participants (Actual) | Interventional | 2012-03-30 | Active, not recruiting |
| A Real-world Study Evaluating the Safety and Efficacy of Tafasitamab in Combination With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma [NCT05883709] | | 15 participants (Anticipated) | Observational | 2023-07-01 | Not yet recruiting |
| Isa-RVD Study: Phase II, Multi-centre, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma [NCT05123131] | Phase 2 | 43 participants (Anticipated) | Interventional | 2022-04-01 | Recruiting |
| Phase I Dose Escalation Study of Velcade in Combination With Lenalidomide in Patients With Relapsed Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) After Allogeneic Stem Cell Transplantation [NCT02312102] | Phase 1 | 22 participants (Actual) | Interventional | 2015-02-28 | Active, not recruiting |
| Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab and Lenalidomide in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) [NCT01754857] | Phase 2 | 36 participants (Actual) | Interventional | 2013-11-12 | Completed |
| A Phase I/II Study of Ublituximab in Combination With Lenalidomide (Revlimid®) in Patients With B-Cell Lymphoid Malignancies Who Have Relapsed or Are Refractory After CD20 Directed Antibody Therapy [NCT01744912] | Phase 1 | 10 participants (Actual) | Interventional | 2012-11-21 | Terminated(stopped due to Sponsor's decision) |
| MInimal Residual Disease Adapted Strategy: Frontline Therapy for Patients Eligible for Autologous Stem Cell Transplantation Less Than 66 Years; a Prospective Study [NCT04934475] | Phase 3 | 791 participants (Actual) | Interventional | 2021-12-08 | Active, not recruiting |
| Optimizing Prolonged Treatment In Myeloma Using MRD Assessment (OPTIMUM) [NCT03941860] | Phase 3 | 510 participants (Anticipated) | Interventional | 2022-02-16 | Active, not recruiting |
| A Prospective, Multicenter, Observational Study in Relapsed and/or Refractory Multiple Myeloma Patients Treated With Ixazomib Plus Lenalidomide and Dexamethasone [NCT03433001] | | 295 participants (Actual) | Observational | 2018-04-02 | Completed |
| A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens [NCT03412565] | Phase 2 | 265 participants (Actual) | Interventional | 2018-04-26 | Active, not recruiting |
| A Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy [NCT02252172] | Phase 3 | 737 participants (Actual) | Interventional | 2015-02-16 | Active, not recruiting |
| An Open-Label, Multicenter, Phase 1b Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Regimens for the Treatment of Subjects With Multiple Myeloma [NCT01998971] | Phase 1 | 242 participants (Actual) | Interventional | 2014-02-18 | Active, not recruiting |
| An Open Label, International, Multicenter, Dose Escalating Phase I/II Trial Investigating the Safety of Daratumumab in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Relapsed and Refractory Multiple Myeloma [NCT01615029] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2012-06-30 | Active, not recruiting |
| A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement [NCT04432714] | Phase 1/Phase 2 | 81 participants (Anticipated) | Interventional | 2020-06-09 | Recruiting |
| A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL [NCT02200848] | Phase 1 | 5 participants (Actual) | Interventional | 2014-04-30 | Terminated(stopped due to Recruitment difficulties and toxicity) |
| A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma [NCT01850524] | Phase 3 | 705 participants (Actual) | Interventional | 2013-04-29 | Completed |
| Efficacy and Safety of Lenalidomide in Combination With R-GemOx in First-line Treatment of Elderly Diffuse Large B Cell Lymphoma [NCT04432402] | | 124 participants (Anticipated) | Interventional | 2020-06-14 | Recruiting |
| Phase II Study of Romidepsin Plus Lenalidomide for Patients With Previously Untreated PTCL [NCT02232516] | Phase 2 | 35 participants (Actual) | Interventional | 2015-06-30 | Active, not recruiting |
| A Phase 3B Randomized Study of Lenalidomide (CC-5013) Plus Rituximab Maintenance Therapy Followed by Lenalidomide Single-Agent Maintenance Versus Rituximab Maintenance in Subjects With Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma [NCT01996865] | Phase 3 | 503 participants (Actual) | Interventional | 2014-04-01 | Active, not recruiting |
| An Open Label, Multicenter, Phase 2, Pilot Study, Evaluating Early Treatment With Bispecific T-cell Redirectors (Teclistamab and Talquetamab) in the Frontline Therapy of Newly Diagnosed High-risk Multiple Myeloma [NCT05849610] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-11-30 | Recruiting |
| Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy (REFRACT): A Randomised Phase II Trial of Investigator Choice Standard Therapy Versus Sequential Novel Therapy Experimental Arms [NCT05848765] | Phase 2 | 284 participants (Anticipated) | Interventional | 2023-09-04 | Recruiting |
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Comparing the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to R-CHOP Versus R-CHOP in Previously Untreated, High-intermediate and High-risk Patients With Newly- [NCT04824092] | Phase 3 | 899 participants (Actual) | Interventional | 2021-05-11 | Active, not recruiting |
| A Phase I Study of Venetoclax + Lenalidomide + Rituximab Hyaluronidase in Relapsed or Refractory (R/R) Indolent Non-Hodgkin's Lymphoma (iNHL). [NCT04447716] | Phase 1 | 30 participants (Anticipated) | Interventional | 2020-10-16 | Recruiting |
| A Phase 1 Study of Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies [NCT04447027] | Phase 1 | 30 participants (Anticipated) | Interventional | 2020-12-17 | Recruiting |
| Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Follo [NCT01415752] | Phase 2 | 373 participants (Actual) | Interventional | 2012-08-09 | Active, not recruiting |
| Phase II Study of Lenalidomide/Rituximab Maintenance for Transplantation Ineligible Patients With Primary CNS Diffuse Large B-cell Lymphoma (Nickname: Lemon-C Study) [NCT04627753] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-11-02 | Recruiting |
| Phase II Trial of Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma [NCT04094142] | Phase 2 | 66 participants (Actual) | Interventional | 2019-07-09 | Completed |
| Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a High Dose Melphalan Conditioning Regimen, With Administration of Interleukin-2, in Patients With Multiple Myeloma [NCT03506802] | Phase 1 | 0 participants (Actual) | Interventional | 2018-07-10 | Withdrawn(stopped due to No Participants Enrolled) |
| A Phase I Study of the Combination of Lenalidomide With the Histone Deacetylase Inhibitor, Vorinostat in Hodgkin and Non Hodgkin's Lymphoma [NCT01116154] | Phase 1 | 30 participants (Anticipated) | Interventional | 2010-05-31 | Terminated(stopped due to Sponsor withdrew support for the study) |
| Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line [NCT01122472] | Phase 3 | 650 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Single Arm Phase II Study to Investigate the Use of Lenalidomide in the Treatment of Patients With Early Stage CLL Associated With Poor Prognostic Factors [NCT01127542] | Phase 2 | 1 participants (Actual) | Interventional | 2010-05-31 | Terminated(stopped due to Potential safety issue of second primary malignancies in patients treated with lenalidomide.) |
| A Phase I, Open-Label Study To Determine The Maximum Tolerated Dose (Mtd) Of The Combination Of Lenalidomide And Cetuximab, And To Evaluate The Efficacy Of This Combination In Subjects With Wild Type K-Ras Metastatic Colorectal Carcinoma [NCT01126450] | Phase 1 | 3 participants (Actual) | Interventional | 2009-10-31 | Terminated(stopped due to low accrual,loss of funding and results from EU study showing drug ineffective.) |
| Effect of Lenalidomide (Revlimid®) in Solid Tumour Patients With Inflammatory Cancer Cachexia Syndrome on Lean Body Mass and Muscle Strength: A Multicenter, Proof-of-concept Study of Fixed Dose or CRP-response-guided Dose of Lenalidomide in Relation to Ne [NCT01127386] | Phase 1/Phase 2 | 200 participants (Actual) | Interventional | 2009-03-31 | Completed |
| Phase II Study of Glofitamab, Poseltinib and Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma [NCT05335018] | Phase 2 | 76 participants (Anticipated) | Interventional | 2022-05-30 | Recruiting |
| A Two Stage Trial of lénalidomide (Revlimid®) : a Phase II Study of lénalidomide as Single Agent in Asymptomatic Ovarian Cancer Patients With Increasing CA 125 in Late Relapse: Followed by a Phase I of lénalidomide in Combination With Carboplatin and Lipo [NCT01111903] | Phase 1/Phase 2 | 67 participants (Actual) | Interventional | 2009-05-31 | Completed |
| EVALUATION OF CHOLECALCIFEROL (VitD3) MAINTENANCE SUPPLEMENTATION IN PATIENTS WITH MULTIPLE MYELOMA (MM) UNDERGOING TRANSPLANTATION AND IN COMBINATION WITH LENALIDOMIDE MAINTENANCE [NCT05846880] | Early Phase 1 | 100 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting |
| A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administrated in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed M [NCT05573802] | Phase 1/Phase 2 | 36 participants (Anticipated) | Interventional | 2023-07-14 | Recruiting |
| A Multi-center, Open Label, Phase 1b/2 Study to Study the Efficacy and Safety of MIL62 Plus Lenalidomide in Subjects With Relapsed/Refractory Follicular Lymphoma or Marginal Zone Lymphoma [NCT04110301] | Phase 1/Phase 2 | 53 participants (Anticipated) | Interventional | 2019-11-28 | Recruiting |
| A Phase I Study of Lenalidomide in Combination With Dexamethasone in Anti-MAG Demyelinating Sensorimotor Neuropathy [NCT03701711] | Phase 1 | 11 participants (Actual) | Interventional | 2018-09-10 | Terminated(stopped due to Higher than expected occurrence of VTE (venous thromboembolic event)) |
| A Phase Ib/IIa Study of Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma [NCT01755975] | Phase 1/Phase 2 | 62 participants (Actual) | Interventional | 2012-12-31 | Completed |
| A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) [NCT04663347] | Phase 1/Phase 2 | 662 participants (Anticipated) | Interventional | 2020-11-03 | Recruiting |
| A Pilot Study of Lenalidomide Maintenance Therapy Following Autologous Stem Cell Transplantation in Patients With Relapsed/Refractory Hodgkin Lymphoma [NCT01207921] | Phase 1 | 28 participants (Actual) | Interventional | 2011-04-28 | Completed |
| Multicenter Phase I Study on the Safety, Anti-tumor Activity and Pharmacology of IPH2101, a Human Monoclonal Anti-KIR, Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse [NCT01217203] | Phase 1 | 15 participants (Actual) | Interventional | 2010-09-30 | Completed |
| A Phase II, Multi-center, Open-label, Repeat-dose Study of Lenalidomide (Revlimid ®) Plus Low-dose Dexamethasone in Patients With Refractory B Cell Lineage Acute Lymphoblastic Leukemia or in Relapse After 2 Lines of Treatment [NCT01116193] | Phase 2 | 10 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Observational, Non-interventional, Multicenter Study Aimed at Collecting Retrospective/Prospective 648/96 Italian Registry Data Related to Lenalidomide (Revlimid®) Prescription to Patients With Myelodysplastic Syndromes [NCT01347944] | | 149 participants (Actual) | Observational | 2011-01-01 | Completed |
| A Randomized Parallel Phase 2 Study of Elotuzumab Plus Lenalidomide (Elo/Rev) for the Treatment of Serologic Relapse/Progression While on Lenalidomide Maintenance for Multiple Myeloma [NCT03411031] | Phase 2 | 18 participants (Actual) | Interventional | 2018-10-04 | Terminated(stopped due to Sponsor no longer providing drug) |
| Clinical Study to Evaluate the Safety and Efficacy of Daratumumab and Carfilzomib-based Induction/Consolidation/Maintenance Therapy in Transplant-eligible, Ultra High-risk, Newly Diagnosed Multiple Myeloma [NCT06140966] | Phase 2 | 54 participants (Anticipated) | Interventional | 2023-10-20 | Recruiting |
| Post Marketing Surveillance on Safety Evaluation of REVLIMID® (Lenalidomide) Treatment of Myelodysplastic Syndromes Associated With a Deletion 5q or Mantle Cell Lymphoma in Korea [NCT04036448] | | 600 participants (Anticipated) | Observational | 2019-08-18 | Active, not recruiting |
| Carfilzomib, Lenalidomide, and Dexamethasone in Newly-Diagnosed Multiple Myeloma: A Clinical and Correlative Phase I/II Dose Escalation Study [NCT02937571] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2016-10-31 | Active, not recruiting |
| Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma [NCT02076009] | Phase 3 | 569 participants (Actual) | Interventional | 2014-05-23 | Active, not recruiting |
| Randomized Phase III Trial Comparing the Frequency of Major Erythroid Response (MER) to Treatment With Lenalidomide (Revlimid�) Alone and in Combination With Epoetin Alfa (Procrit�) in Subjects With Low- or Intermediate-1 Risk MDS and Symptomatic Anemia [NCT00843882] | Phase 3 | 247 participants (Actual) | Interventional | 2009-01-29 | Active, not recruiting |
| A Randomized Phase III Trial of CC-5013 (Lenalidomide, NSC-703813) and Low Dose Dexamethasone (LLD) Versus Bortezomib (PS-341, NSC-681239), Lenalidomide and Low Dose Dexamethasone (BLLD) for Induction, in Patients With Previously Untreated Multiple Myelom [NCT00644228] | Phase 3 | 525 participants (Actual) | Interventional | 2008-04-01 | Active, not recruiting |
| An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) Versus Melphalan, Prednisone and Lenalidomide (Revlimid(TM))(MPR) in Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for High-Dose T [NCT00602641] | Phase 3 | 306 participants (Actual) | Interventional | 2008-02-29 | Active, not recruiting |
| A Phase III Randomized, Double-Blind Study of Maintenance Therapy With CC-5013 (NSC # 703813) or Placebo Following Autologous Stem Cell Transplantation for Multiple Myeloma [NCT00114101] | Phase 3 | 460 participants (Actual) | Interventional | 2004-12-15 | Active, not recruiting |
| A Randomized Phase III Study of CC-5013 Plus Dexamethasone Versus CC-5013 Plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide Plus Dexamethasone Salvage Therapy for Non-Responders [NCT00098475] | Phase 3 | 452 participants (Actual) | Interventional | 2004-11-03 | Active, not recruiting |
| An Open-Label Phase 2 Study of Lenalidomide (Revlimid) in Combination With Oral Dexamethasone in the Treatment of Previously Untreated, Symptomatic Patients With Chronic Lymphocytic Leukemia (CLL) [NCT01133743] | Phase 2 | 31 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Phase II Study of the Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib and Dexamethasone Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma [NCT02441686] | Phase 2 | 45 participants (Anticipated) | Interventional | 2015-12-31 | Active, not recruiting |
| An Open Label, Multicenter, Phase II Study of Belantamab Mafodotin in Combination With VRd for the Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Patients [NCT04802356] | Phase 2 | 50 participants (Anticipated) | Interventional | 2021-04-07 | Recruiting |
| A National, Open-label, Multicenter, Randomized, Comparative Phase IIb Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) [NCT01237249] | Phase 2 | 250 participants (Actual) | Interventional | 2011-02-28 | Completed |
| Phase 2 Trial of LDE225 and Lenalidomide Maintenance Post Autologous Stem Cell Transplant for Multiple Myeloma [NCT02086552] | Phase 2 | 28 participants (Actual) | Interventional | 2014-01-17 | Completed |
| Phase Ib of CC-5013 and Paclitaxel in Patients With Advanced Solid Tumors [NCT01155505] | Phase 1 | 28 participants (Anticipated) | Interventional | 2009-11-30 | Active, not recruiting |
| Lenalidomide Based Immunotherapy Efficacy Related Molecular Biomarker in Diffuse Large B-cell Lymphoma [NCT03715296] | | 200 participants (Anticipated) | Observational [Patient Registry] | 2018-10-18 | Recruiting |
| Phase 1/2 Study of Lenalidomide and Cetuximab in Patients With Advanced Solid Tumors [NCT01166035] | Phase 1/Phase 2 | 20 participants (Anticipated) | Interventional | 2010-03-31 | Recruiting |
| Efficacy and Safety Study of Rituximab, Methotrexate and Lenalidomide Chemotherapy（R2-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma：a Single Arm, Multicenter, Phase 2 Study [NCT04934579] | Phase 2 | 17 participants (Actual) | Interventional | 2020-01-01 | Completed |
| A Phase I Study of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) in Patients With Advanced Cancers [NCT01183663] | Phase 1 | 180 participants (Actual) | Interventional | 2010-08-31 | Completed |
| IFM2008: Frontline Therapy in de Novo Multiple Myeloma Patients Under 65, (a Phase 2 Multicenter Trial) [NCT01206205] | Phase 2 | 31 participants (Actual) | Interventional | 2009-08-31 | Completed |
| Lenalidomide, Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone (R2-GOD) in Treatment of Relapse/Refractory DLBCL:A Phase I Study [NCT03795571] | Phase 1 | 12 participants (Anticipated) | Interventional | 2019-01-01 | Recruiting |
| A Phase 1, Open-label, Randomized, Three-period, Two-way Crossover Study in Healthy Subjects to Evaluate the Bioavailability of a Test Lenalidomide Oral Suspension Relative to the Reference Capsule Formulation and to Assess the Effect of Food on the Bioav [NCT02521714] | Phase 1 | 28 participants (Anticipated) | Interventional | 2015-08-14 | Completed |
| A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly [NCT03319667] | Phase 3 | 475 participants (Actual) | Interventional | 2017-12-07 | Active, not recruiting |
| A Phase II Study of Daily Alternating Thalidomide and Lenalidomide Therapy Plus Rituximab (ThRiL) as Initial Treatment for Patients With CLL [NCT01125176] | Phase 2 | 15 participants (Actual) | Interventional | 2012-03-30 | Completed |
| Enhancement of Cetuximab-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC) With Lenalidomide in Advanced Solid Tumors: A Phase I/IB Study [NCT01254617] | Phase 1 | 24 participants (Actual) | Interventional | 2011-02-10 | Completed |
| A Phase 1 Study of MLN9708 in Japanese Patients With Relapsed and/or Refractory Multiple Myeloma [NCT04272775] | Phase 1 | 14 participants (Actual) | Interventional | 2012-06-05 | Terminated(stopped due to Business Decision; No Safety Or Efficacy Concerns) |
| A Clinical Trial of Programmed Cell Death Protein 1(PD1) Antibody and Lenalidomide as a Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis or Chronic Active EBV Infection(CAEBV) [NCT04084626] | Phase 3 | 40 participants (Anticipated) | Interventional | 2019-09-15 | Recruiting |
| A Multicentric, Phase II Trial of Lenalidomide, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis (AL) Newly Diagnosed, Not Candidates for Hematopoietic Stem Cell Transplantation [NCT01194791] | Phase 2 | 30 participants (Anticipated) | Interventional | 2010-10-31 | Completed |
| A Single Arm, Multi-center, Phase II Clinical Trial of Rituximab, Lenalidomide Combined With High-dose Methotrexate and Temozolomide (RL-MT) in the First-line Treatment for Patients With Primary Central Nervous System Lymphoma [NCT04737889] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-01-13 | Recruiting |
| Randomized Phase II Trial on Fitness- and Comorbidity- Tailored Treatment in Elderly Patients With Newly Diagnosed Primary CNS Lymphoma (FIORELLA Trial) [NCT03495960] | Phase 2 | 208 participants (Anticipated) | Interventional | 2019-06-15 | Recruiting |
| Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM): A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM) [NCT03815279] | Phase 2 | 80 participants (Anticipated) | Interventional | 2019-06-24 | Enrolling by invitation |
| A Phase 1 Study of Lenalidomide in Combination With Vorinostat in Pediatric Patients With High Grade or Progressive Central Nervous System Tumors [NCT03050450] | Phase 1 | 8 participants (Actual) | Interventional | 2016-08-10 | Terminated(stopped due to Lack of feasibility to accrue patients in allotted time.) |
| Randomized Phase II Trial Seeking the Most Promising Drug Association With Azacitidine- in Higher Risk Myelodysplastic Syndromes [NCT01342692] | Phase 2 | 320 participants (Anticipated) | Interventional | 2011-06-30 | Active, not recruiting |
| A Randomized, Multicenter, Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma [NCT01080391] | Phase 3 | 792 participants (Actual) | Interventional | 2010-07-14 | Completed |
| A Phase 3 Multicenter, Randomized, Double-blind, Placebo-Controlled, First Line Maintenance Study Of Lenalidomide (Revlimid®) In Patients With Mantle-Cell Lymphoma [NCT01021423] | Phase 3 | 9 participants (Actual) | Interventional | 2010-04-01 | Terminated(stopped due to Terminated by sponsor due to new unpublished data that rendered the current design of the study no longer clinically relevant. There were no safety concerns.) |
| A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study To Compare The Efficacy And Safety of Lenalidomide (Revlimid®) Versus Placebo In Subjects With Transufsion-Dependent Anemia Due to IPSS Low Or Imtermidate-1 Risk My [NCT01029262] | Phase 3 | 239 participants (Actual) | Interventional | 2010-01-26 | Completed |
| A Prospective Phase 2 Study to Assess the Minimal Residual Disease After Ixazomib Plus Lenalidomide Plus Dexamethasone (IRd) Treatment for Newly Diagnosed Transplant Eligible Myeloma Patients [NCT03376672] | Phase 2 | 120 participants (Actual) | Interventional | 2018-05-31 | Active, not recruiting |
| Response Adapted Therapy With Bortezomib/Dexamethasone Followed by Addition of Lenalidomide in Non Responders as Initial Treatment for Patients With Multiple Myeloma [NCT01919086] | Phase 2 | 30 participants (Actual) | Interventional | 2013-08-31 | Active, not recruiting |
| "A PHASE 3 OPEN-LABEL RANDOMIZED STUDY TO COMPARE THE EFFICACY AND SAFETY OF RITUXIMAB PLUS LENALIDOMIDE (CC-5013) VERSUS RITUXIMAB PLUS CHEMOTHERAPY FOLLOWED BY RITUXIMAB IN SUBJECTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA The RELEVANCE Trial (Ritu [NCT01650701] | Phase 3 | 1,030 participants (Actual) | Interventional | 2012-02-29 | Active, not recruiting |
| Carfilzomib, Daratumumab, Lenalidomide and Dexamethasone as First Line Treatment in Multiple Myeloma [NCT04288765] | Phase 3 | 0 participants (Actual) | Interventional | 2020-03-01 | Withdrawn(stopped due to incomplete recruitment) |
| Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy With Maintenance Lenalidomide and Rituximab in Relapsed/Refractory CLL/SLL [NCT00974233] | Phase 2 | 34 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Phase I Study of Safety, Tolerability and Immunological Effects of SVN53-67/M57-KLH in Patients With Multiple Myeloma Receiving Lenalidomide Maintenance Therapy [NCT02334865] | Phase 1 | 18 participants (Actual) | Interventional | 2017-04-13 | Active, not recruiting |
| Phase 1b Multicenter Dose Escalation Study of Carfilzomib With Lenalidomide and Dexamethasone for Safety and Activity in Relapsed Multiple Myeloma [NCT00603447] | Phase 1 | 84 participants (Actual) | Interventional | 2008-05-31 | Completed |
| A Phase 3 Study to Evaluate the Efficacy and Safety of Docetaxel and Prednisone With or Without Lenalidomide in Subjects With Castrate-Resistant Prostate Cancer (CRPC) [NCT00988208] | Phase 3 | 1,059 participants (Actual) | Interventional | 2009-11-11 | Completed |
| A Phase 1/2, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of Lenalidomide in Combination With Sunitinib in Subjects With Advanced or Metastatic Renal Cell Carcinoma [NCT00975806] | Phase 1/Phase 2 | 16 participants (Actual) | Interventional | 2009-09-01 | Terminated(stopped due to MTD determined sub-optimal as efficacious treatment for renal cell carcinoma.) |
| Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Concomitant Evaluation of Safety and Efficacy. [NCT00738829] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2008-10-31 | Completed |
| A Prospective, Multicenter, Single Arm, Phase II Clinical Trial of Clarithromycin, Lenalidomide and Dexamethasone (BiRd Regimen) in the Treatment of the First Relapsed Multiple Myeloma [NCT04063189] | Phase 2 | 100 participants (Anticipated) | Interventional | 2017-03-21 | Recruiting |
| A Multicentre Phase II Study of the Efficacy and Safety of Lenalidomide in High-risk Myeloid Disease (High-risk MDS and AML) With a Karyotype Including Del(5q) or Monosomy 5 [NCT00761449] | Phase 2 | 28 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Phase Ib / II Open-Label Stduy of APG-2575 Monotherapy or in Combination With Lenalidomide / Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma [NCT04674514] | Phase 1/Phase 2 | 48 participants (Anticipated) | Interventional | 2021-04-13 | Recruiting |
| A Randomized Phase III Trial Assessing the Benefit of the Addition of Isatuximab to Lenalidomide / Bortezomib / Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma [NCT03617731] | Phase 3 | 662 participants (Actual) | Interventional | 2018-10-18 | Active, not recruiting |
| Lenalidomide, Adriamycin, Dexamethasone (RAD) Versus Lenalidomide, Bortezomib, Dexamethasone (VRD) for Induction in Newly Diagnosed Multiple Myeloma Followed by Response-adapted Consolidation and Lenalidomide Maintenance - A Randomized Multicenter Phase I [NCT01685814] | Phase 3 | 406 participants (Anticipated) | Interventional | 2012-05-31 | Active, not recruiting |
| A Phase II Trial to Evaluate the Safety and Activity of Single-agent Lenalidomide Given as Maintenance Therapy After Response to Second-line Therapy in Patients With Relapsed DLBCL, Not Eligible for High-dose Chemotherapy and ASCT [NCT00799513] | Phase 2 | 47 participants (Anticipated) | Interventional | 2009-10-31 | Recruiting |
| A Phase 3, Multicenter, Randomized, Openlabel, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) Versus Chlorambucil as First-Line Therapy for Previously Untreated Elderly Patients With B-Cell Chronic Lymphocytic Leukemia (The Or [NCT00910910] | Phase 3 | 450 participants (Actual) | Interventional | 2009-10-13 | Completed |
| Safety And Efficacy Of Lenalidomide As Maintenance Therapy In Patients With Newly Diagnosed Multiple Myeloma Following A Tandem Autologous-Allogeneic Transplant [NCT01264315] | Phase 2 | 53 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Open-Label, One Arm Pilot Investigation of Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas [NCT00704691] | Early Phase 1 | 1 participants (Actual) | Interventional | 2008-06-30 | Terminated(stopped due to Closed due to futility with only 1 patient accrued) |
| Open-Label, Multi-Center Phase I Dose-Escalation Study With Lenalidomide In Patients With Acute Myeloid Leukemia [NCT00839059] | Phase 1 | 14 participants (Actual) | Interventional | 2009-01-31 | Terminated(stopped due to Results of an interim analysis and a hardly ongoing enrolment in the last 10 months in all six participating centres) |
| "A Phase I Pilot Study of Immunotherapy Using Lenalidomide Plus Bystander Vaccine in Patients With High-Risk Myelodysplastic Syndrome (MDS)" [NCT00840931] | Phase 1 | 22 participants (Actual) | Interventional | 2009-02-02 | Completed |
| Single-arm, Multi-center Clinical Study of PD-1 Antibody, Chidamide, Lenalidomide and Gemcitabine for Peripheral T-cell Lymphoma [NCT04040491] | Phase 4 | 100 participants (Anticipated) | Interventional | 2019-09-01 | Recruiting |
| Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid in Combination With Polatuzumab (ViPOR-P) in Relapsed/Refractory B-cell Lymphoma [NCT04739813] | Phase 1 | 55 participants (Anticipated) | Interventional | 2021-07-09 | Recruiting |
| A Phase 1 Study of Lenalidomide in Combination With EPOCH Chemotherapy for HTLV-Associated Adult T-Cell Leukemia-Lymphoma (ATLL) [NCT04301076] | Phase 1 | 30 participants (Anticipated) | Interventional | 2021-08-31 | Recruiting |
| Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM) [NCT03289299] | Phase 2 | 87 participants (Actual) | Interventional | 2018-05-25 | Active, not recruiting |
| Phase II Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma [NCT01729091] | Phase 2 | 72 participants (Anticipated) | Interventional | 2013-06-10 | Active, not recruiting |
| A Randomized Phase II Dose Finding Study of Revlimid™ and Melphalan in Patients With Previously Untreated Multiple Myeloma [NCT00305812] | Phase 2 | 51 participants (Actual) | Interventional | 2006-03-09 | Completed |
| Selinexor Combined With Prednisone, Etoposide, and Lenalidomide as Introductive Treatment Following Immune-chemotherapy as Consolidated Therapy for Refractory Diffuse Large B-cell Lymphoma With p53 and/or c-Myc Expression [NCT05498636] | Phase 1/Phase 2 | 67 participants (Anticipated) | Interventional | 2022-10-01 | Not yet recruiting |
| A Single-arm, Phase Ⅰ/Ⅱ Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of ATG-010 in Combination With Lenalidomide and Rituximab (R2) in Adult Patients With Relapsed/Refractory DLBCL and iNHL Who Are Ineligible for High-dose Chemother [NCT05265975] | Phase 1/Phase 2 | 84 participants (Anticipated) | Interventional | 2022-04-07 | Recruiting |
| Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia [NCT01373229] | Phase 1 | 21 participants (Actual) | Interventional | 2012-01-31 | Completed |
| A Phase I/II Trial of Romidepsin, Rituximab and Lenalidomide (R3) in Relapsed/Refractory B Cell Lymphomas Including Transformed Follicular Lymphoma [NCT02281279] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2016-10-31 | Withdrawn |
| A Phase 1 Open-Label Study of the Safety and Efficacy of PD 0332991 (Palbociclib) in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT02030483] | Phase 1 | 9 participants (Actual) | Interventional | 2014-02-28 | Terminated(stopped due to The company providing one of the study drugs withdrew its support due to low enrollment. Therefore, we had to close the study due to lack of funding.) |
| A Phase 1 Pharmacokinetic and Tolerability Study of Oral MLN9708 Plus Lenalidomide and Dexamethasone in Adult Asian Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01645930] | Phase 1 | 43 participants (Actual) | Interventional | 2012-12-17 | Completed |
| A Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of XmAb13676 (Plamotamab) Combined With Tafasitamab Plus Lenalidomide Versus Tafasitamab Plus Lenalidomide in Subjects With Relapsed or Refractory Diffuse Large B-Cell [NCT05328102] | Phase 2 | 3 participants (Actual) | Interventional | 2022-04-25 | Terminated(stopped due to The study has been terminated early by the sponsor due to business decision.) |
| A Pilot Study Evaluating Lenalidomide and CC-486 in Combination With Radiotherapy For Patients With Plasmacytoma (LENAZART Study) [NCT04174196] | Phase 2 | 20 participants (Anticipated) | Interventional | 2019-11-19 | Recruiting |
| Phase I/II Study of Lenalidomide (Revlimid), All-trans Retinoic Acid (ATRA) and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma [NCT01985477] | Phase 1 | 2 participants (Actual) | Interventional | 2013-12-31 | Terminated(stopped due to Terminated Phase I due to slow accrual without progression to Phase II.) |
| "An Intensive Program With Quadruplet Induction and Consolidation Plus Tandem Autologous Stem Cell Transplantation in Newly Diagnosed High Risk Multiple Myeloma Patients: a Phase II Study of the Intergroupe Francophone du Myélome IFM 2018-04" [NCT03606577] | Phase 2 | 50 participants (Anticipated) | Interventional | 2019-07-30 | Active, not recruiting |
| A Phase II Study of the Efficacy and Safety of Lenalidomide Plus ICE in the Treatment of Refractory and Relapsed Diffuse Large B-cell Lymphoma [NCT03367143] | Phase 2 | 39 participants (Anticipated) | Interventional | 2016-12-31 | Active, not recruiting |
| Immuno-PRISM (PRecision Intervention Smoldering Myeloma): A Randomized Phase II Platform Study of Select Immunotherapies for High-Risk Smoldering Myeloma [NCT05469893] | Phase 2 | 51 participants (Anticipated) | Interventional | 2022-08-10 | Recruiting |
| A Prospective, Single-center, Phase II Study of Venetoclax/Selinexor Plus VRD Combined With CART-ASCT-CART2 Treatment in Patients With Newly Diagosed Primary Plasma Cell Leukemia [NCT05870917] | Phase 2 | 20 participants (Anticipated) | Interventional | 2023-04-25 | Recruiting |
| The Efficacy and Safety of Zanubrutinib, Rituximab and Lenalidomide (ZR2) Versus Rituximab Combined With Low-dose CHOP (R-miniCHOP) in the Treatment of Unfit or Frail de Novo Diffuse Large B-cell Lymphoma Patients Aged Older Than or Equal to 70 Years: A M [NCT05179733] | Phase 3 | 280 participants (Anticipated) | Interventional | 2022-03-02 | Recruiting |
| A Phase 1, Open Label, Multiple Dose, Dose Escalation and Expansion Study of Bruton Tyrosine Kinase (BTK) Inhibitor, Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lympho [NCT04436107] | Phase 1 | 67 participants (Anticipated) | Interventional | 2020-09-11 | Recruiting |
| A Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus De [NCT03544281] | Phase 1/Phase 2 | 152 participants (Actual) | Interventional | 2018-09-20 | Active, not recruiting |
| A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide With or Without Elotuzumab (NSC-764479) for Newly Diagnosed High Risk Multiple Myeloma (HRMM) [NCT01668719] | Phase 1/Phase 2 | 142 participants (Actual) | Interventional | 2012-11-30 | Active, not recruiting |
| A Phase I Trial of Brentuximab Vedotin in Combination With Lenalidomide in Relapsed or Refractory Diffuse Large B-cell Lymphoma [NCT02086604] | Phase 1 | 37 participants (Actual) | Interventional | 2014-09-18 | Completed |
| Phase 2 Trial of Belantamab Mafodotin Consolidation Treatment in Patients With Multiple Myeloma and MRD Positivity After Autologous Stem Cell Transplantation [NCT04876248] | Phase 2 | 20 participants (Anticipated) | Interventional | 2023-12-15 | Recruiting |
| A Phase Ib/II, Open-Label, Multicenter Study With a Non-Randomized Stage Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab Plus Lenalidomide (+Len), and a Randomized Stage Evaluating the Safety, Tolerability, and Pharmacokinetics of S [NCT04246086] | Phase 1/Phase 2 | 187 participants (Anticipated) | Interventional | 2020-08-12 | Active, not recruiting |
| An Open-Label, Single-Arm, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) in Patients With Multiple Myeloma Previously Receiving a Bortezomib-Based Induction Regim [NCT03173092] | Phase 4 | 141 participants (Actual) | Interventional | 2017-09-20 | Active, not recruiting |
| An Expanded Access Program for Elotuzumab in Combination With Lenalidomide Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT02368301] | | 0 participants | Expanded Access | | No longer available |
| An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma [NCT02180711] | Phase 1 | 113 participants (Actual) | Interventional | 2014-12-29 | Active, not recruiting |
| Phase 3B, Randomized Trail of Revlimid® (Lenalidomide) Versus Placebo Maintenance Therapy Following Melphalan Prednisone Velcade (Bortezomib) Induction Therapy In Newly Diagnosed Multiple Myeloma [NCT02112175] | Phase 3 | 46 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Multicenter Clinical Study of Orelabrutinib Combined With Lenalidomide and Rituximab (OR2) in the Treatment of Recurrent and Refractory CD20+ B-cell Lymphoma [NCT05014100] | Phase 2 | 55 participants (Anticipated) | Interventional | 2021-09-01 | Not yet recruiting |
| Phase 2 Trial of Intensive Chemo-immunotherapy With Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Relapsed/Refractory Myeloma in the Context of Salvage Autologous Hematopoietic Cell Transplantation [NCT03556332] | Phase 2 | 41 participants (Actual) | Interventional | 2018-07-02 | Active, not recruiting |
| "A Phase III Randomized Trial for Newly Diagnosed Multiple Myeloma (NDMM) Patients Considered Frail or in a Subset of Intermediate Fit Comparing Upfront Three-Drug Induction Regimens Followed by Double or Single-Agent Maintenance" [NCT05561387] | Phase 3 | 510 participants (Anticipated) | Interventional | 2023-10-12 | Recruiting |
| A Phase Ib/II Open-Label Study of APG-2575 in Combination With Novel Therapeutic Regimens in Subjects With Relapsed or Refractory Multiple Myeloma and Immunoglobin Light Chain Amyloidosis [NCT04942067] | Phase 1/Phase 2 | 108 participants (Anticipated) | Interventional | 2021-12-23 | Recruiting |
| A Phase 2, Open Label, Randomized Trial Evaluating Ixazomib Compared to Ixazomib-Lenalidomide Combination Maintenance Therapy for Frontline Multiple Myeloma Patients [NCT03733691] | Phase 2 | 19 participants (Actual) | Interventional | 2019-03-01 | Terminated(stopped due to Insufficient enrollment) |
| A Phase 3, Open Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide Therapy in Relapsed/Refr [NCT06149286] | Phase 3 | 470 participants (Anticipated) | Interventional | 2023-12-18 | Recruiting |
| A Randomized, Double-blind, Placebo-Controlled, Active-Comparator, Multicenter, Phase 3 Study of Brentuximab Vedotin or Placebo in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) [NCT04404283] | Phase 3 | 240 participants (Actual) | Interventional | 2020-08-20 | Active, not recruiting |
| Sub-cutaneous Rituximab-miniCHOP Versus Sub-cutaneous Rituximab-miniCHOP + Lenalidomide (R2-miniCHOP) in Diffuse Large B Cell Lymphoma for Patients of 80 Years Old or More. A Multicentric Phase III Study of the LYSA Association [NCT02128061] | Phase 3 | 250 participants (Actual) | Interventional | 2014-08-31 | Completed |
| A Phase 1, Randomized, Dose and Schedule Evaluation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Belantamab Mafodotin Administered in Combination With Standard of Care in Participants With Newly Diagnosed Mu [NCT04091126] | Phase 1 | 144 participants (Anticipated) | Interventional | 2019-12-18 | Recruiting |
| A Prospective, Single-arm, Multicenter Clinical Study of Mitoxantrone Hydrochloride Liposome Combined With Rituximab and Lenalidomide in the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma [NCT05575973] | Phase 2 | 55 participants (Anticipated) | Interventional | 2022-10-10 | Not yet recruiting |
| A Pilot Study Examining Selinexor's Ability to Overcome Resistance in Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy. [NCT04519476] | Phase 1 | 22 participants (Anticipated) | Interventional | 2020-11-01 | Recruiting |
| A Phase II Study of Brentuximab Vedotin and Lenalidomide in Relapsed and Refractory T-Cell Lymphomas [NCT03409432] | Phase 2 | 26 participants (Actual) | Interventional | 2018-03-16 | Active, not recruiting |
| Alternating the Administration of Ixazomib and Lenalidomide as Maintenance Therapy After Autologous Transplant for Treating Multiple Myeloma [NCT02619682] | Phase 2 | 30 participants (Actual) | Interventional | 2015-12-30 | Active, not recruiting |
| A Protocol to Assess the Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Administration of Low-dose Lenalidomide (STAR-LLD) for the Treatment of Multiple Myeloma (MM) [NCT06087653] | Phase 1/Phase 2 | 6 participants (Anticipated) | Interventional | 2023-10-02 | Recruiting |
| Phase III Study of Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) Versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL [NCT04483739] | Phase 3 | 302 participants (Actual) | Interventional | 2020-09-25 | Active, not recruiting |
| Phase II Study of Lenalidomide Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma [NCT01472562] | Phase 2 | 38 participants (Actual) | Interventional | 2011-07-29 | Completed |
| International, Multi-center, Open-label, Treatment Extension Study in Patients With Multiple Myeloma Who Are Still Benefitting From Isatuximab-based Therapy Following Completion of a Phase 1, 2, or 3 Parental Study [NCT05669989] | Phase 2 | 70 participants (Anticipated) | Interventional | 2023-04-05 | Recruiting |
| A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PDL1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia [NCT02733042] | Phase 1/Phase 2 | 106 participants (Actual) | Interventional | 2016-05-11 | Completed |
| Phase II Trial of Lenalidomide in Patients With Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT) Type [NCT00923663] | Phase 2 | 16 participants (Anticipated) | Interventional | 2009-07-31 | Recruiting |
| Lenalidomide, Bendamustine and Rituximab as First-line Therapy for Patients Over 65 Years With Mantle Cell Lymphoma - a Nordic Lymphoma Group Trial [NCT00963534] | Phase 1/Phase 2 | 51 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Phase I/II Trial of Lenalidomide Combined With Cyclophosphamide and Intermediate Dose Dexamethasone in Patients With Primary (AL) Systemic Amyloidosis [NCT00981708] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma [NCT04653246] | Phase 2 | 43 participants (Anticipated) | Interventional | 2021-07-13 | Recruiting |
| A Phase I Trial Evaluating the Safety and Efficacy of Vorinostat (Zolinza ®) + RVD (Lenalidomide {Revlimid ®} + Bortezomib {Velcade ®} + Dexamethasone) for Patients With Newly Diagnosed Multiple Myeloma [NCT01038388] | Phase 1 | 30 participants (Actual) | Interventional | 2010-01-15 | Completed |
| A Phase II Trial of MRD (Melphalan, Lenalidomide and Dexamethasone) for Patients With AL Amyloidosis [NCT00679367] | Phase 2 | 16 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Phase I/II Trial of Lenalidomide in Combination With Vorinostat and Dexamethasone as Therapy in Relapsed or Refractory Patients With Peripheral T-Cell Non-Hodgkin's Lymphoma (PTCL) [NCT00972842] | Phase 1/Phase 2 | 20 participants (Anticipated) | Interventional | 2009-09-30 | Terminated(stopped due to slow recruitment) |
| Phase II Study for the Determination of Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome With Favorable Risk Profile [NCT00977132] | Phase 2 | 23 participants (Actual) | Interventional | 2009-10-31 | Terminated(stopped due to delayed recruitment) |
| Phase II Study of Revlimid®, Oral Cyclophosphamide and Prednisone (RCP) for Patients With Newly Diagnosed Multiple Myeloma [NCT00540644] | Phase 2 | 70 participants (Actual) | Interventional | 2007-10-31 | Completed |
| REVLIMID® Drug Use Examination [NCT02556905] | | 624 participants (Actual) | Observational | 2011-03-09 | Completed |
| Salvage Treatment With Lenalidomide and Dexamethaosne(LEN-DEX) in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL) [NCT00786851] | Phase 2 | 33 participants (Actual) | Interventional | 2008-07-31 | Completed |
| Phase I/II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation Followed by Maintenance Therapy With Lenalidomide and Sirolimus in Patients With High-Risk Multiple Myeloma [NCT01303965] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2011-02-07 | Terminated(stopped due to Slow accrual) |
| The Official Title is A Multi-center, Randomized, Parallel-group, Double-blind, Placebo Controlled Study of CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma. [NCT00424047] | Phase 3 | 351 participants (Actual) | Interventional | 2003-01-01 | Completed |
| Lenalidomide and Dexamethasone (Rd) Versus Clarithromycin [Biaxin®] / Lenalidomide [Revlimid®] / Dexamethasone (BiRd) as Initial Therapy in Multiple Myeloma [NCT02516696] | Phase 3 | 12 participants (Actual) | Interventional | 2016-02-29 | Terminated(stopped due to low enrollment) |
| A Randomized Phase II Trial of Rituximab Versus Lenalidomide (REVLIMID™, Cc-5013) (IND#73034) Versus Rituximab + Lenalidomide in Recurrent Follicular Non-Hodgkin Lymphoma (NHL) That is Not Rituximab-Refractory [NCT00238238] | Phase 2 | 97 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase 2 Trial of Lenalidomide (Revlimid)-Dexamethasone + Rituximab in Recurrent Small B-Cell Non-Hodgkin Lymphomas (NHL) Resistant to Rituximab [NCT00783367] | Phase 2 | 50 participants (Actual) | Interventional | 2008-07-31 | Completed |
| A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis [NCT00890552] | | 25 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Phase IB Study of Escalating Doses of REVLIMID in Association With R-CHOP (R2-CHOP) in the Treatment of B-cell Lymphoma [NCT00901615] | Phase 1/Phase 2 | 108 participants (Actual) | Interventional | 2009-01-06 | Completed |
| A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Lenalidomide (Revlimid®) as Maintenance Therapy for Patients With B-Cell Chronic Lymphocytic Leukemia Following Second-Line Therapy (T [NCT00774345] | Phase 3 | 317 participants (Actual) | Interventional | 2009-01-27 | Completed |
| Carfilzomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma: a Clinical and Correlative Pilot Study [NCT01572480] | Phase 2 | 55 participants (Actual) | Interventional | 2012-05-29 | Active, not recruiting |
| Lenalidomide in the Treatment of Mucosal Behçet's Syndrome [NCT05449548] | | 42 participants (Anticipated) | Interventional | 2023-04-01 | Recruiting |
| A Phase 2 Evaluation of Daratumumab-Based Treatment in Newly Diagnosed Multiple Myeloma Patients With Renal Insufficiency [NCT04352205] | Phase 2 | 25 participants (Anticipated) | Interventional | 2020-05-07 | Recruiting |
| A Phase 2 Study of Subcutaneous Daratumumab in Combination With Dose-Attenuated Bortezomib, Lenalidomide, and Dexamethasone in Elderly Newly Diagnosed Multiple Myeloma Patients [NCT04052880] | Phase 2 | 38 participants (Anticipated) | Interventional | 2019-10-24 | Recruiting |
| A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis [NCT00564889] | Phase 2 | 35 participants (Actual) | Interventional | 2007-12-31 | Completed |
| A Prospective Single-center Study on the Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS [NCT06004765] | Phase 4 | 138 participants (Anticipated) | Interventional | 2023-08-31 | Not yet recruiting |
| A Phase II Trial of the Anti -PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) + Lenalidomide + Dexamethasone as Post Autologous Transplant Consolidation in Patients With High-risk Multiple Myeloma [NCT02906332] | Phase 2 | 12 participants (Actual) | Interventional | 2016-12-12 | Terminated(stopped due to FDA Hold Due to Updated Risks) |
| A Randomized Phase III Study to Compare Bortezomib, Melphalan, Prednisone (VMP) With High Dose Melphalan Followed by Bortezomib, Lenalidomide, Dexamethasone (VRD) Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma [NCT01208766] | Phase 3 | 1,503 participants (Actual) | Interventional | 2011-01-31 | Active, not recruiting |
| Combination of Lenalidomide and Sintilimab for Patients With Relapsed/Refractory NK/T-cell Lymphoma Who Failed Pegaspargase-based Regimens: a Single Arm, Open, Phase II Study [NCT04231370] | Phase 2 | 20 participants (Anticipated) | Interventional | 2020-04-01 | Recruiting |
| A Randomized Phase II Study of Lenalidomide Maintenance Therapy in AML Patients Aged > 60 Years in CR1 or Higher and < 60 Years in CR2 or Higher [NCT00957385] | Phase 2 | 24 participants (Actual) | Interventional | 2008-06-30 | Completed |
| The Efficacy and Safety of ZR2 Versus R-CHOP-like Regimen for Elderly Patients With Newly Diagnosed Diffuse Large B Cell Lymphoma. [NCT05428670] | Phase 2 | 150 participants (Anticipated) | Interventional | 2022-06-15 | Recruiting |
| MCLENA-1: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Lenalidomide in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease [NCT04032626] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-07-22 | Recruiting |
| Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients (SABLe): An Investigator Sponsored Trial [NCT04717700] | Phase 2 | 50 participants (Anticipated) | Interventional | 2021-08-18 | Recruiting |
| A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eli [NCT02513186] | Phase 1 | 90 participants (Actual) | Interventional | 2015-09-30 | Active, not recruiting |
| A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined With MOR00208 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) [NCT02399085] | Phase 2 | 81 participants (Actual) | Interventional | 2016-03-29 | Completed |
| A Phase 2, Multicenter, Randomized Open-Label Study To Determine the Efficacy of Lenalidomide (Revlimid®) Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma [NCT00875667] | Phase 2 | 254 participants (Actual) | Interventional | 2009-04-30 | Completed |
| Phase 1 Study of Elotuzumab in Combination With Autologous Stem Cell Transplantation and Lenalidomide Maintenance for Multiple Myeloma [NCT02655458] | Phase 1 | 15 participants (Actual) | Interventional | 2016-01-31 | Completed |
| Rituximab, Bendamustine and Lenalidomide in Patients With Aggressive B-cell Lymphoma Not Eligible for High Dose Chemotherapy or Anthracycline-Based Therapy. A Phase I/II Trial. [NCT00987493] | Phase 1/Phase 2 | 49 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Lenalidomide Maintenance Therapy in Patients With MDS or AML With Cytogenetic Abnormalities Involving Monosomy 5 or del5q After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) [NCT00720850] | Phase 2 | 10 participants (Actual) | Interventional | 2008-04-30 | Terminated(stopped due to Low recruitment, scientific rationale not applicable anymore to all patients and possible induction of GvHD by the study drug) |
| Phase II Study of Pegylated Liposomal Doxorubicin (Doxil®), Low Frequency Dexamethasone and Revlimid® (Dd-R) in Newly Diagnosed Multiple Myeloma [NCT00617591] | Phase 2 | 57 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Multicentre, Single-arm, Open-label Safety Study of Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma [NCT00420849] | Phase 3 | 587 participants (Actual) | Interventional | 2006-11-30 | Completed |
| Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3×CD20) in Japanese Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A Phase 1/2, Open-Label, Dose-Escalation Trial With Expansion Cohorts [NCT04542824] | Phase 1/Phase 2 | 102 participants (Anticipated) | Interventional | 2020-08-20 | Active, not recruiting |
| A Phase II Study of Lenalidomide (REVLIMID®) in Combination With Rituximab for Patients With CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab [NCT00609869] | Phase 2 | 29 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Randomized, Open-label, Multi-center Phase III Trial Comparing Tisagenlecleucel to Standard of Care in Adult Participants With Relapsed or Refractory Follicular Lymphoma (FL) [NCT05888493] | Phase 3 | 108 participants (Anticipated) | Interventional | 2023-10-02 | Recruiting |
| A Phase 1 Study of ANV419 as Monotherapy, and ANV419 in Combination With Daratumumab or With Lenalidomide Plus Low-Dose Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma (OMNIA-2) [NCT05641324] | Phase 1 | 4 participants (Actual) | Interventional | 2023-02-10 | Terminated(stopped due to The study was ended due to a lack of recruitment) |
| Phase 1b/2, Open-Label Study to Evaluate Safety and Tolerability of Epcoritamab in Combination With Anti-Neoplastic Agents in Subjects With Non-Hodgkin Lymphoma [NCT05283720] | Phase 2 | 394 participants (Anticipated) | Interventional | 2022-06-14 | Recruiting |
| Phase I/II Study of Lenalidomide (Revlimid), Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R2CHOP) Chemoimmunotherapy in Patients With Newly Diagnosed Diffuse Large Cell and Follicular Grade IIIA/B B Cell Lymphoma [NCT00670358] | Phase 1/Phase 2 | 138 participants (Actual) | Interventional | 2008-08-25 | Active, not recruiting |
| A Phase 2 Study of Teclistamab in Combination With Daratumumab or Lenalidomide in Elderly Patients With Newly Diagnosed Multiple Myeloma [NCT05572229] | Phase 2 | 74 participants (Anticipated) | Interventional | 2023-09-30 | Not yet recruiting |
| A Randomized, Controlled, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Orelabrutinib Plus Lenalidomide and Rituximab (R2) Versus Placebo Plus R2 in Relapsed/Refractory Marginal Zone Lymphoma [NCT06082102] | Phase 3 | 324 participants (Anticipated) | Interventional | 2023-10-25 | Not yet recruiting |
| Phase I Clinical Trial of Bcl2 Inhibitor Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) in t(11;14) Multiple Myeloma [NCT06042725] | Phase 1 | 100 participants (Anticipated) | Interventional | 2023-12-01 | Not yet recruiting |
| Minimal Residual Disease Guided Maintenance Therapy With Belantamab Mafodotin and Lenalidomide After Autologous Hematopoietic Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma [NCT05091372] | Phase 2 | 94 participants (Anticipated) | Interventional | 2022-12-01 | Recruiting |
| [NCT00902915] | Phase 2 | 50 participants (Anticipated) | Interventional | 2009-05-31 | Active, not recruiting |
| Randomized Phase III Trial of Consolidation Therapy With Bortezomib (Velcade®)-Lenalidomide (Revlimid®) -Dexamethasone (VRD) Versus Bortezomib (Velcade®)-Dexamethasone (VD) for Patients With Multiple Myeloma Who Have Completed a Dexamethasone Based Induct [NCT00522392] | Phase 3 | 48 participants (Actual) | Interventional | 2007-09-30 | Terminated(stopped due to Slow accrual) |
| An Open, Randomized Clinical Phase I/II Trial to Investigate Maximum Tolerated Dose, Efficacy, and Safety of Lenalidomide/Low-dose Dexamethasone in Combination With Continuous Oral Cyclophosphamide Compared to Lenalidomide/Low-dose Dexamethasone Combined [NCT01019174] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Maintenance Therapy With Lenalidomide, Dexamethasone and Clarithromycin (Biaxin) Following Autologous/Syngeneic Transplant for Multiple Myeloma [NCT00445692] | Phase 2 | 32 participants (Actual) | Interventional | 2007-01-10 | Completed |
| A Phase II Study of Thalidomide (THALOMID®), Clarithromycin (BIAXIN®), Lenalidomide(REVLIMID®), and Dexamethasone (DECADRON®) for Subjects With Newly Diagnosed Multiple Myeloma [NCT00538733] | Phase 2 | 26 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Phase II Study of Bortezomib, Melphalan, Prednisone (VMP) Followed by Lenalidomide Maintenance vs. VMP Without Maintenance in Myeloma Patients Not Eligible to High-dose Chemotherapy and Autologous Stem Cell Transplantation [NCT02145598] | Phase 2/Phase 3 | 85 participants (Actual) | Interventional | 2013-08-31 | Terminated(stopped due to Insufficient recruitment) |
| A Single-arm, Multi-center, Phase II Clinical Trial of R-CHOP Combined With Lenalidomide in the First-line Treatment for Patients With Medium to High Risk/High Risk Diffuse Large B Cell Lymphoma [NCT04214626] | Phase 2 | 60 participants (Actual) | Interventional | 2020-01-02 | Active, not recruiting |
| Phase 2 Study With Minimal Residual Disease (MRD) Driven Adaptive Strategy in Treatment for Newly Diagnosed Multiple Myeloma (MM) With Upfront Daratumumab-based Therapy [NCT04140162] | Phase 2 | 57 participants (Actual) | Interventional | 2020-10-05 | Active, not recruiting |
| A Phase I Dose Escalation Study of the Combination of Lenalidomide (Revlimid®), Dexamethasone and Cyclophosphamide in Patients Refractory or Relapsing From Stable Disease With Multiple Myeloma [NCT00915408] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Phase 2 Study Assessing Feasibility and Tolerance of the Combination of Elotuzumab, Lenalidomide and Dexamethasone in Induction, Consolidation and Maintenance Treatment of Transplant-Eligible Patients Newly Diagnosed With Multiple Myeloma [NCT02843074] | Phase 2 | 53 participants (Actual) | Interventional | 2016-09-21 | Completed |
| Efficacy of Alternating Immunochemotherapy Consisting of R-CHOP + R-HAD vs R-CHOP Alone, Followed by Maintenance Therapy Consisting of Additional Lenalidomide + Rituximab vs Rituximab Alone for Older Patients With Mantle Cell Lymphoma [NCT01865110] | Phase 3 | 623 participants (Actual) | Interventional | 2013-11-30 | Active, not recruiting |
| A Phase Ib/II Study of Escalating Doses of Revlimid in Association With R-CHOP (R2-CHOP) in the Treatment of B-cell Lymphoma [NCT01393756] | Phase 2 | 80 participants (Actual) | Interventional | 2010-12-31 | Completed |
| A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function [NCT00790842] | Phase 1/Phase 2 | 63 participants (Actual) | Interventional | 2009-01-21 | Terminated(stopped due to Slow enrollment) |
| Open-Label, Single-Arm Study of the Safety and Efficacy of CC-5013 Monotherapy for Subjects With Multiple Myeloma: A Companion Study for Studies THAL-MM-003, CC-5013-MM-009, and CC-5013-MM-010 [NCT00622336] | Phase 3 | 330 participants (Actual) | Interventional | 2003-04-01 | Completed |
| Phase II Trial of High Dose Lenalidomide in Patients With MDS and AML With Trilineage Dysplasia (AML-TLD) [NCT00867308] | Phase 2 | 32 participants (Actual) | Interventional | 2009-07-31 | Terminated(stopped due to Lack of efficacy) |
| Phase II Trial of CC-5013 (Lenalidomide, Revlimid®) in Patients With Cutaneous T-Cell Lymphoma [NCT00466921] | Phase 2 | 33 participants (Actual) | Interventional | 2005-04-19 | Completed |
| A Single-Arm, Open-Label Study of the Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Red Blood Cell Transfusion-Dependent Myelodysplastic Syndromes [NCT00840827] | Phase 2 | 6 participants (Actual) | Interventional | 2008-12-31 | Terminated(stopped due to Lack of efficacy.) |
| A Multi-center, Single-arm, Open Label Study to Assess the Efficacy and Safety of Anti-PD-1 Antibody (Penpulimab) Plus Lenalidomide, Rituximab, Gemcitabine and Oxaliplatin (R2-GemOx) in Patients With Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLB [NCT05186558] | Phase 2 | 54 participants (Anticipated) | Interventional | 2022-05-15 | Not yet recruiting |
| A Phase 2 Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL) [NCT00751296] | Phase 2 | 27 participants (Actual) | Interventional | 2006-08-31 | Terminated(stopped due to Seven years of follow-up & final analysis done in Dec 2012.) |
| A Phase 2, Multicenter, Single-Arm, Open-Label Study To Determine The Efficacy And Safety Of Single-Agent Lenalidomide (Revlimid®) In Patients With Mantel Cell NHL Who Have Relapsed Or Progressed After Treatment With Bortezomib Or Are Refractory To Bortez [NCT00737529] | Phase 2 | 134 participants (Actual) | Interventional | 2008-12-22 | Completed |
| Phase I Trial of Irinotecan Plus Lenalidomide in Adult Patients With Recurrent Glioblastoma Multiforme [NCT00671801] | Phase 1 | 24 participants (Actual) | Interventional | 2008-04-29 | Terminated(stopped due to Toxicity) |
| A Phase 1b/2, Multicenter, Open-label, Dose-escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed Multiple Myeloma [NCT00742560] | Phase 2 | 101 participants (Actual) | Interventional | 2008-08-31 | Completed |
| A First-in-human, Dose-escalation Followed by Expansion Study to Assess the Safety and Preliminary Efficacy of a Bispecific Antibody OT-A201 as Monotherapy and in Combination Therapy in Patients With Selected Hematological Malignancies and Solid Tumors [NCT05828459] | Phase 1 | 150 participants (Anticipated) | Interventional | 2023-07-10 | Recruiting |
| Desensitization of Immunomodulating Agent-Related Hypersensitivity Reactions as a Means to Provide Therapeutic Options in the Management of Plasma Cell Disorders (DeHyperPCD) [NCT03959358] | Phase 2 | 10 participants (Actual) | Interventional | 2020-07-03 | Completed |
| A Phase II Clinical Trial for Untreated Patients With Multiple Myeloma Eligible for Stem Cell Transplant: Lenalidomide (Revlimid®) Plus Low-dose Dexamethasone (Ld x 4 Cycles) Then Stem Cell Collection Followed by Randomization to Continued Ld or Stem Cell [NCT00807599] | Phase 2 | 67 participants (Actual) | Interventional | 2008-12-10 | Completed |
| A Phase II Study of Lenalidomide Revlimid(Registered Trademark) in Previously Treated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma [NCT00439231] | Phase 2 | 33 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Lenalidomide for Advanced Hepatocellular Cancer:A Phase II Trial [NCT00717756] | Phase 2 | 41 participants (Actual) | Interventional | 2009-01-31 | Completed |
| Phase 2 Study of the Initial and Post-Transplant Treatment With Carfilzomib, Lenalidomide and Low Dose Dexamethasone (CRd) in Transplant Candidates With Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy [NCT01816971] | Phase 2 | 76 participants (Actual) | Interventional | 2013-01-31 | Active, not recruiting |
| A Phase 2, Open-Label Study To Evaluate The Efficacy And Safety Of Lenalidomide In Combination With Cetuximab In Pretreated Subjects With K-Ras Mutant Metastatic Colorectal Cancer [NCT01032291] | Phase 2 | 51 participants (Actual) | Interventional | 2009-12-31 | Terminated(stopped due to A business decision not to continue with Phase 2b based on non-safety observations during proof of concept phase.) |
| A Phase II Study of Lenalidomide (Revlimid®) as Second Line Therapy in Patients With Chronic Graft-Versus-Host Disease (GVHD) [NCT00675441] | Phase 2 | 5 participants (Actual) | Interventional | 2008-04-30 | Terminated(stopped due to Terminated due to slow accrual.) |
| A Phase I Study of a Combination of 5-azacitidine Followed by Lenalidomide in High-risk MDS or Relapsed/Refractory AML Patients With Cytogenetic Abnormalities Including -5 or Del(5q) [NCT00923234] | Phase 1 | 0 participants | Interventional | 2009-06-30 | Terminated(stopped due to The primary objective has already been answered with the number of recruited patients.) |
| A Safety Confirmation Study On Lenalidomide With Dexamethasone In Japanese Patients With Previously Treated Multiple Myeloma [NCT00928486] | Phase 3 | 25 participants (Actual) | Interventional | 2009-04-28 | Completed |
| A Phase II Study of Rituximab, Lenalidomide, and Ibrutinib Combined With Chemotherapy for Patients With High Risk Diffuse Large B-Cell Lymphoma [NCT02636322] | Phase 2 | 60 participants (Actual) | Interventional | 2016-03-29 | Completed |
| A Phase II Study of Lenalidomide for Adult Histiocyte Disorders [NCT02523040] | Phase 2 | 12 participants (Anticipated) | Interventional | 2015-08-31 | Active, not recruiting |
| Phase I/II Trial of Ibrutinib, Dexamethasone, and Lenalidomide as Initial Therapy for Transplant Ineligible Multiple Myeloma Patients [NCT03015792] | Phase 1/Phase 2 | 18 participants (Actual) | Interventional | 2017-03-10 | Terminated(stopped due to Per CS0139535 -submitter stated we can update status to Admin complete- low accrual reasoning) |
| Early Patient Access Single Named Patient Program for the Use of Ulocuplumab for the Treatment of Multiple Myeloma [NCT02666209] | | 0 participants | Expanded Access | | No longer available |
| Phase I/II Study of Lenalidomide (Revlimid), Thalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma [NCT00966693] | Phase 1/Phase 2 | 77 participants (Actual) | Interventional | 2009-08-25 | Completed |
| Phase I/II Study of Oral Lenalidomide and High Dose Melphalan Supported by Autologous Peripheral Blood Stem Cell Infusion for Patients With Multiple Myeloma [NCT01142232] | Phase 1/Phase 2 | 60 participants (Actual) | Interventional | 2010-08-27 | Completed |
| A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab as Maintenance Therapy Following Standard Chemotherapy for Patients With High/High-intermediate Risk Diffuse Large B-Cell Lymphoma [NCT00765245] | Phase 2 | 44 participants (Actual) | Interventional | 2008-10-31 | Completed |
| A Combination of Lenalidomide and Rituximab as Front Line Therapy for the Treatment of Elderly Frail Patients Evaluated in CGA With Diffuse Large B-cells Non-Hodgkin Lymphoma. A Phase II Study of the Fondazione Italiana Linfomi (FIL) [NCT02955823] | Phase 2 | 68 participants (Actual) | Interventional | 2016-09-30 | Completed |
| A Pharmacokinetic And Pharmacodynamic Study Of Oral Lenalidomide (Revlimid) In Subjects With Low- Or Intermediate-1-Risk Myelodysplastic Syndromes [NCT00910858] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Phase 2 Trial of Intracycle Sequential Ofatumumab and Lenalidomide for the Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab [NCT01123356] | Phase 2 | 21 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Phase 1b Study of Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-cell Lymphoma, CD30-positive Peripheral T-cell Lymphoma, or CD30-positive Hodgkin Lymphoma [NCT03302728] | Phase 1 | 6 participants (Actual) | Interventional | 2018-08-30 | Completed |
| A Multicenter, Phase Ib/II Study That Combines Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients [NCT04539236] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2021-11-09 | Recruiting |
| Carfilzomib - Lenalidmide - Dexamethasone (KRd) Versus Lenalidomi - Dexamethasone (Rd) in Newly Diagnosed Myeloma Patients Not Eligible for Autologous Stem Cell Transplantation: a Randomized Phas III Trial [NCT04096066] | Phase 3 | 84 participants (Actual) | Interventional | 2019-07-01 | Active, not recruiting |
| A Phase 1/2, Open-label Study of Valemetostat in Combination With Rituximab and Lenalidomide in Relapsed or Refractory Follicular Lymphoma [NCT05683171] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2023-05-19 | Recruiting |
| A Phase 1b/2, Open-Label, Multicenter Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [NCT05222555] | Phase 1/Phase 2 | 51 participants (Anticipated) | Interventional | 2022-07-19 | Recruiting |
| Smart Stop: A Phase II Trial of Rituximab, Lenalidomide, Acalabrutinib, Tafasitamab Prior to and With Standard Chemotherapy for Patients With Newly Diagnosed DLBCL [NCT04978584] | Phase 2 | 60 participants (Anticipated) | Interventional | 2022-03-03 | Recruiting |
| Monoclonal Antibody-Based Sequential Therapy for Deep Remission in Multiple Myeloma - MASTER Trial [NCT03224507] | Phase 2 | 123 participants (Actual) | Interventional | 2018-03-14 | Completed |
| An Open-Label Phase I Study of the Safety of and Efficacy of RAD001 in Combination With Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma [NCT00729638] | Phase 1 | 28 participants (Actual) | Interventional | 2008-06-30 | Completed |
| Phase 1 Trial of Flavopiridol in Combination With Lenalidomide in Patients With Relapsed or Refractory B-Cell CLL/SLL [NCT00735930] | Phase 1 | 39 participants (Actual) | Interventional | 2008-08-31 | Completed |
| The Efficacy and Safety of Lenalidomide (Revlimid®) Monotherapy in Red Blood Cell Transfusion Dependent Subjects With Myelodysplastic Syndrome Associated With Del (5q) Cytogenetic Abnormality [NCT00874978] | Phase 2 | 36 participants (Anticipated) | Interventional | 2005-01-31 | Completed |
| A Phase II Study of the Efficacy and Safety of Lenalidomide Combined to Escalating Doses of Chemotherapy in Intermediate-2-or High Risk MDS and AML With Del 5q [NCT00885508] | Phase 2 | 85 participants (Actual) | Interventional | 2009-02-28 | Active, not recruiting |
| A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients [NCT00699842] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2008-07-31 | Terminated(stopped due to Administratively terminated per FDA recommendation) |
| Phase II Trial of Bevacizumab Combined With Lenalidomide and Dexamethasone (BEV/REV/DEX) in Relapsed or Refractory Multiple Myeloma [NCT00410605] | Phase 2 | 39 participants (Actual) | Interventional | 2006-11-30 | Completed |
| The Efficacy and Safety of Zanubrutinib, Lenalidomide and Rituximab (ZR2) Regimen in Elderly Treatment-naive Patients With Diffuse Large B-cell Lymphoma (DLBCL) [NCT04460248] | Phase 2 | 40 participants (Anticipated) | Interventional | 2020-07-22 | Active, not recruiting |
| An Open-label, Phase II Study of Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis [NCT00607581] | Phase 2 | 21 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A Phase I/II Study of Combination Dasatinib and Lenalidomide in Purine Analogue-Failed Chronic Lymphocytic Leukemia [NCT00829647] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2009-01-31 | Withdrawn(stopped due to Unable to enroll) |
| A Phase II Study of Revlimid in Combination With Rituximab as Initial Treatment for Patients With Indolent Non-Hodgkin's Lymphoma (NHL) [NCT00695786] | Phase 2 | 156 participants (Actual) | Interventional | 2008-06-10 | Completed |
| A Phase 3 Randomized, Open-Label Multicenter Study of Zanubrutinib (BGB-3111) Plus Anti-CD20 Antibodies Versus Lenalidomide Plus Rituximab in Patients With Relapsed/Refractory Follicular or Marginal Zone Lymphoma [NCT05100862] | Phase 3 | 750 participants (Anticipated) | Interventional | 2022-03-10 | Recruiting |
| Single-arm, Multi-center Clinical Study of PD-1 Antibody, Chidamide, Lenalidomide and Etoposide for Relapsed or Refractory Natural Killer/T Cell Lymphoma [NCT04038411] | Phase 4 | 50 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| A Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis [NCT00883623] | Phase 2 | 50 participants (Actual) | Interventional | 2009-04-30 | Completed |
| Phase 1b/2, Open-Label Trial to Evaluate Safety and Preliminary Efficacy of Epcoritamab As Monotherapy or Combined With Standard-of-Care Therapies in Chinese Subjects With B-Cell Non-Hodgkin Lymphoma [NCT05201248] | Phase 1 | 49 participants (Actual) | Interventional | 2022-03-10 | Active, not recruiting |
| A Randomized, Open-label, Phase 3 Study Comparing Once-weekly vs Twice-weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (A.R.R.O.W.2) [NCT03859427] | Phase 3 | 454 participants (Actual) | Interventional | 2019-05-08 | Completed |
| Phase I Trial of Maintenance Lenalidomide in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome Post Allogeneic Bone Marrow Transplantation [NCT01433965] | Phase 1 | 16 participants (Actual) | Interventional | 2012-08-08 | Completed |
| Phase II Study To Evaluate The Safety And Efficacy Of Lenalidomide For The Treatment Of Refractory Cutaneous Lupus [NCT01408199] | Phase 4 | 15 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Phase 1/2 Study of VELCADE® (Bortezomib), Dexamethasone, and Revlimid® (Lenalidomide) Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma [NCT00507442] | Phase 1/Phase 2 | 158 participants (Actual) | Interventional | 2007-08-31 | Completed |
| An Open-Label, Non-Comparative, Two-Cohort, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Pomalidomide and Dexamethasone (IPd, Cohort A) or With Lenalidomide and Dexamethasone (IRd, Cohort B) in Pati [NCT05183139] | Phase 4 | 0 participants (Actual) | Interventional | 2022-06-30 | Withdrawn(stopped due to Business decision (no enrollment)) |
| Phase I/II Double Blinded Randomized Study to Determine the Tolerability and Efficacy of 2 Different Doses of Revlimid (CC-5013, Lenalidomide) in Biochemically Relapsed Prostate Cancer Patients (M0) After Local Treatment [NCT00348595] | Phase 1/Phase 2 | 77 participants (Actual) | Interventional | 2006-07-20 | Completed |
| A Phase Ib Multiple Ascending Dose Study of BMS-833923 Alone or in Combination With Lenalidomide (Revlimid) Plus Dexamethasone or in Combination With Bortezomib (Velcade) in Subjects With Relapsed or Refractory Multiple Myeloma [NCT00884546] | Phase 1 | 27 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Phase I/II Study of Lenalidomide (RevlimidTM ) and GM-CSF in Androgen Independent Prostate Cancer [NCT00939510] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2005-07-31 | Completed |
| Phase I Trial of AVD Plus Lenalidomide (Revlimid) in Elderly Intermediate or Advanced Stage Hodgkin Lymphoma Patients [NCT01056679] | Phase 1 | 30 participants (Anticipated) | Interventional | 2010-04-30 | Completed |
| A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, an [NCT00689936] | Phase 3 | 1,623 participants (Actual) | Interventional | 2008-08-21 | Completed |
| Phase I/II Study Of The Combination Of Lenalidomide With High-Dose Melphalan For Autologous Transplant in Patients With Multiple Myeloma [NCT01079936] | Phase 1/Phase 2 | 61 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Phase I/II Trial of Combination of Lenalidomide (Revlimid, LEN) and Autologous Mature Dendritic Cells Pulsed With α-galactosyl Ceramide (α-GalCer; KRN7000) in Myeloma [NCT00698776] | Phase 1 | 6 participants (Actual) | Interventional | 2009-04-30 | Completed |
| [NCT00779922] | Phase 2 | 39 participants (Actual) | Interventional | 2008-11-30 | Completed |
| "Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: A Phase 2 Study" [NCT00744536] | Phase 2 | 20 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Dose-finding Study of Lenalidomide as Maintenance Therapy in Multiple Myeloma After Allogeneic Stem Cell Transplantation [NCT00778752] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Phase II Trial of Lenalidomide as a Treatment for Neuropathy Associated With Nonmalignant Monoclonal Gammopathy of Undetermined Significance (MGUS) [NCT00665652] | Phase 2 | 8 participants (Actual) | Interventional | 2008-04-30 | Terminated(stopped due to The study has been suspended for slower than anticipated enrollment to date.) |
| A Phase 2 Study of Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone (LR-CD) for Untreated Low Grade Non-Hodgkin Lymphoma Requiring Therapy [NCT00784927] | Phase 2 | 36 participants (Actual) | Interventional | 2008-11-30 | Completed |
| Efficacy and Safety of Velcade Plus Dexamethasone (VD), VD+Cyclophosphamide or VD Plus Lenalidomide in MMY Patients Who Are Refractory or Have Relapsed After Their Primary Therapy for MMY and Have Achieved Stable Disease After 4 Cycles of VD [NCT00908232] | Phase 2 | 163 participants (Actual) | Interventional | 2008-05-31 | Completed |
| A Single-center Clinical Trial to Evaluate the Efficacy and Safety of Colchicine Combined With Conventional Therapy in Multiple Myeloma Patients [NCT05802992] | Phase 3 | 30 participants (Anticipated) | Interventional | 2022-03-30 | Recruiting |
| Phase I/II Trial of Lenalidomide in Combination With Liposomal Doxorubicin for the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer [NCT00903630] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 2009-04-30 | Terminated(stopped due to lack of funding) |
| A Multicenter, Single-arm Study to Assess the Safety, Pharmacokinetics and Efficacy of Lenalidomide in Japanese Subjects With Low- or Intern=Mediate-1-risk Myelodysplastic Syndromes (MDS) Associated With a Deletion 5 (q31-33) Abnormality and Symptomatic A [NCT00812968] | Phase 2 | 11 participants (Actual) | Interventional | 2007-09-01 | Completed |
| A Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Single-Agent Lenalidomide (Revlimid®) in Subjects With Relapsed or Refractory T-Cell Non-Hodgkin's Lymphoma [NCT00655668] | Phase 2 | 54 participants (Actual) | Interventional | 2008-03-01 | Terminated(stopped due to Decision not to pursue as single agent in the study population.) |
| A Phase I Single Arm Dose Escalation Study of the Combination of Dasatinib (Sprycel®) With Lenalidomide (Revlimid®) and Dexamethasone in Subjects With Relapsed and/ or Refractory Multiple Myeloma [NCT00560391] | Phase 1 | 35 participants (Actual) | Interventional | 2008-05-31 | Completed |
| A Phase II Study Evaluating the Toxicity and Efficacy of Single Agent Lenalidomide (Revlimid®) in Chemotherapy-Naïve Androgen-Independent Prostate Cancer Patients [NCT00654186] | Phase 2 | 32 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A Phase I Study of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT00642954] | Phase 1 | 31 participants (Actual) | Interventional | 2008-02-13 | Completed |
| A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Follicular and Relapsed/Refractory Aggressive (DLBCL and MCL) B-cell Lymphoma [NCT01582776] | Phase 1/Phase 2 | 317 participants (Actual) | Interventional | 2012-10-03 | Completed |
| A Genetic Risk-Stratified, Randomized Phase II Study of Four Fludarabine/Antibody Combinations for Patients With Symptomatic, Previously Untreated Chronic Lymphocytic Leukemia [NCT00602459] | Phase 2 | 418 participants (Actual) | Interventional | 2008-01-15 | Completed |
| A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for First-Line Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL) [NCT00628238] | Phase 2 | 80 participants (Anticipated) | Interventional | 2008-02-29 | Recruiting |
| Phase I/II Trial of Azacitidine Plus Lenalidomide in the Treatment of Acute Myeloid Leukemia [NCT01016600] | Phase 1/Phase 2 | 31 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Frontline Lenalidomide for AL Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide [NCT04298372] | Phase 3 | 30 participants (Anticipated) | Interventional | 2019-02-20 | Recruiting |
| Lenalidomide Observational Study in Patients With Mantle Lymphoma in Relapse/Refraction. Spanish Programme RRMCL Results. [NCT04109872] | | 25 participants (Anticipated) | Observational | 2018-09-15 | Recruiting |
| Phase I/II Study Evaluating Rituximab, Lenalidomide, and Bortezomib in the First-Line or Second-Line Treatment of Patients With Mantle Cell Lymphoma [NCT00633594] | Phase 1/Phase 2 | 39 participants (Actual) | Interventional | 2008-06-30 | Completed |
| Post-Autologous Transplant Maintenance With Isatuximab and Lenalidomide in Minimal Residual Disease Positive Multiple Myeloma [NCT05344833] | Phase 2 | 50 participants (Anticipated) | Interventional | 2023-01-05 | Recruiting |
| A Phase 1/2 Multicenter, Open-label Study to Determine the Recommended Dose and Regimen of Durvalumab (MEDI4736) in Combination With Lenalidomide (LEN) With and Without Dexamethasone (DEX)in Subjects With Newly Diagnosed Multiple Myeloma (NDMM) [NCT02685826] | Phase 1/Phase 2 | 56 participants (Actual) | Interventional | 2016-04-25 | Completed |
| A Pilot Study of Lenalidomide Alternating With Ipilimumab Post Allogeneic and Autologous Stem Cell Transplantation [NCT01919619] | Phase 2 | 41 participants (Actual) | Interventional | 2013-11-04 | Active, not recruiting |
| Combination of Lenalidomide and Rituximab in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL-SLL) as Initial Treatment or Subsequent Therapy [NCT01446133] | Phase 2 | 120 participants (Anticipated) | Interventional | 2011-12-12 | Active, not recruiting |
| A Phase II Study of IRD (Ixazomib, Lenalidomide, & Dexamethasone) for Consolidation Therapy Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma [NCT02253316] | Phase 2 | 236 participants (Actual) | Interventional | 2015-01-20 | Active, not recruiting |
| [NCT00968331] | Phase 2 | 25 participants (Actual) | Interventional | 2009-03-31 | Terminated(stopped due to The EC withdrawn the approval becuase of possible conflicts of interests between our Institute and Supporter (Celgene)) |
| Evaluation of Efficacy and Safety of Lenalidomide (Revlimid®) in Patients With POEMS Syndrome [NCT00971685] | Phase 2 | 16 participants (Anticipated) | Interventional | 2009-07-31 | Recruiting |
| A Phase 2 Study of Isatuximab in Combination With Bortezomib, Cyclophosphamide and Dexamethasone Followed by Isatuximab and Lenalidomide Maintenance in Newly Diagnosed Patients With Multiple Myeloma and Severe Renal Impairment (EAE116) [NCT05147493] | Phase 2 | 51 participants (Anticipated) | Interventional | 2022-04-30 | Not yet recruiting |
| Lenalidomide, Melphalan, Prednisone, and Thalidomide (RMPT) for Relapsed/Refractory Multiple Myeloma [NCT00961467] | Phase 2 | 44 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Phase I Clinical Trial of Bendamustine, Lenalidomide and Rituximab in B-Cell Lymphoid Malignancies [NCT00864942] | Phase 1 | 28 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Phase II Study of the Efficacy and Safety of Lenalidomide in Adult Subjects With Intermediate-2-or Higt Risk Myelodysplastic Syndrome(MDS) Associated With a Deletion (DEL) 5q [31] [NCT00424229] | Phase 2 | 49 participants | Interventional | 2006-10-31 | Recruiting |
| An Open, Single-arm, Multi-center Clinical Trial of Molecular Subtype-guided R-MINE+X Regimen in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) [NCT05784987] | | 60 participants (Anticipated) | Interventional | 2023-04-15 | Not yet recruiting |
| BrUOG 401: A Phase 2 Study of Mosunetuzumab With Lenalidomide Augmentation as First-line Therapy for Follicular and Marginal Zone Lymphoma [NCT04792502] | Phase 2 | 52 participants (Anticipated) | Interventional | 2022-07-14 | Recruiting |
| Maintenance Lenalidomide Therapy After Autologous Stem Cell Transplant in Patients With High Risk Relapsed/Refractory Lymphomas [NCT01575860] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2012-04-30 | Completed |
| A Phase Ib, Multi-center, Open-label, Dose-escalation Study of Oral LBH589 When Administered in Combination With Oral Lenalidomide & Dexamethasone in Adult Patients With Multiple Myeloma [NCT00532675] | Phase 1 | 46 participants (Actual) | Interventional | 2008-04-22 | Completed |
| Phase II Study of Lenalidomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme. [NCT00165477] | Phase 2 | 23 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Randomised Comparison of Daily 25 mg Versus 5 mg Lenalidomide as Maintenance Therapy After High-dose Therapy and Autologous Stem Cell Transplantation in Patients With Multiple Myeloma [NCT00891384] | Phase 3 | 194 participants (Actual) | Interventional | 2009-04-01 | Completed |
| Pharmacogenomic Study to Predict Survival, Best Response and Toxicity in Newly Diagnosed Myeloma Patients Above the Age of 65 Treated With Either a Combination of Melphalan-prednisone-thalidomide or Lenalidomide-dexamethasone [NCT00907452] | | 143 participants (Actual) | Interventional | 2009-07-29 | Completed |
| S0833, Modified Total Therapy 3 (TT3) for Newly Diagnosed Patients With Multiple Myeloma (MM): A Phase II SWOG Trial for Patients Aged ≤ 65 Years [NCT01055301] | Phase 2 | 0 participants (Actual) | Interventional | 2011-07-31 | Withdrawn(stopped due to lack of accrual) |
| A Phase II Study of Lenalidomide (REVLIMID, NSC-703813) for Previously Untreated Non-M3, Deletion 5q Acute Myeloid Leukemia (AML) in Patients Age 60 or Older Who Decline Remission Induction Chemotherapy [NCT00352365] | Phase 2 | 41 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Phase III, Multicentre, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Parallel Group Study To Determine The Efficacy And Safety Of Lenalidomde (Revlimid®) In Combination With Melphalan And Prednisone Versus Placebo Plus Melphalan And Prednisone In [NCT00405756] | Phase 3 | 459 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Phase II, Multicenter, Single-Arm, Open-Label Study To Evaluate The Safety And Efficacy Of Single-Agent Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma [NCT00413036] | Phase 2 | 217 participants (Actual) | Interventional | 2006-06-30 | Completed |
| Phase I Study of Bendamustine in Combination With Lenalidomide (CC-5013) and Dexamethasone in Patients With Refractory or Relapsed Multiple Myeloma [NCT01042704] | Phase 1 | 29 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase I/II Trial of Maintenance Therapy With Lenalidomide and Rituximab Following High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B-cell Non-Hodgkin Lymphoma [NCT01045928] | Phase 1 | 5 participants (Actual) | Interventional | 2010-01-31 | Terminated(stopped due to Extreme toxicity in Phase I, study did not proceed to Phase II) |
| A Randomized Phase 2 Study of Daratumumab-Selinexor-Velcade-Dexamethasone (Dara-SVD) for High-Risk Newly Diagnosed Multiple Myeloma [NCT06169215] | Phase 2 | 82 participants (Anticipated) | Interventional | 2024-02-20 | Not yet recruiting |
| A RANDOMIZED, 2-ARM, PHASE 3 STUDY OF ELRANATAMAB (PF-06863135) VERSUS LENALIDOMIDE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA AFTER UNDERGOING AUTOLOGOUS STEM-CELL TRANSPLANTATION [NCT05317416] | Phase 3 | 760 participants (Anticipated) | Interventional | 2022-03-25 | Recruiting |
| A Phase I/II Trial of CHOEP Chemotherapy Plus Lenalidomide as Front Line Therapy for Patients With Stage II, III and IV Peripheral T-Cell Non-Hodgkin's Lymphoma [NCT02561273] | Phase 1/Phase 2 | 54 participants (Actual) | Interventional | 2015-09-28 | Completed |
| Third-line Therapy of Multiple Myeloma With Lenalidomide in Combination With Pioglitazone, Dexamethasone and Metronomic Low-dose Chemotherapy With Treosulfan [NCT01010243] | Phase 1/Phase 2 | 54 participants (Anticipated) | Interventional | 2009-10-31 | Recruiting |
| A PHASE 2, SINGLE ARM STUDY TO DETERMINE THE SAFETY AND EFFICACY OF AZACITIDINE, AND LENALIDOMIDE IN HIGHER RISK MYELODYSPLASTIC SYNDROME [NCT01053806] | Phase 2 | 6 participants (Anticipated) | Interventional | 2011-08-31 | Recruiting |
| Phase II Trial of Lenalidomide Maintenance After High-dose Methotrexate-based Immunochemotherapy in Patients With Primary Central Nervous System Lymphoma [NCT05260619] | Phase 2 | 28 participants (Anticipated) | Interventional | 2022-04-01 | Recruiting |
| Phase 1 Dose-Ranging Study of Ezatiostat Hydrochloride (Telintra®, TLK199 Tablets)in Combination With Lenalidomide (Revlimid®)in Patients With Non-Deletion(5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS) [NCT01062152] | Phase 1 | 19 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients With Prostate Cancer Progressive After Androgen Deprivation [NCT00460031] | Phase 2 | 34 participants (Actual) | Interventional | 2006-09-01 | Completed |
| A Phase I Study of Lenalidomide Therapy Prior to Re-induction Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine (MEC) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML) [NCT01904643] | Phase 1 | 17 participants (Actual) | Interventional | 2014-02-28 | Terminated(stopped due to Accrual factor) |
| A Randomized, National, Open-label, Multicenter, Phase III Trial Studying Induction Therapy With Bortezomib/Lenalidomide/Dexamethasone (VRD-GEM), Followed by High-dose Chemotherapy With Melphalan-200 (MEL-200) Versus Busulfan-melphalan (BUMEL), and Consol [NCT01916252] | Phase 3 | 460 participants (Anticipated) | Interventional | 2013-09-30 | Completed |
| A Phase II Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Combination Lenalidomide (Revlimid®) With Rituximab in Subjets With Relapsed or Refractory Diffuse Large b Cell Non-Hodgkin's Lymphoma. [NCT01939327] | Phase 2 | 34 participants (Actual) | Interventional | 2013-09-30 | Completed |
| Rituximab, Methotrexate, Procarbazine, Vincristine, Lenalidomide (RL-MPV) Followed by BBC (BCNU, Busulfan, Cyclophosphamide) High-dose Chemotherapy With Auto-HCT and Maintenance Therapy With Nivolumab in Newly Diagnosed Primary CNS Lymphoma [NCT05425654] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-05-17 | Recruiting |
| A Non-interventional, Observational Post-marketing Registry of Multiple Myeloma Adult Patients Treated With Revlimid (Lenalidomide) in China [NCT01947309] | | 176 participants (Actual) | Observational | 2013-11-30 | Terminated(stopped due to Business Decision) |
| A Study of Low-dose Lenalidomide After Non-myeloablative Allogeneic Stem Cell Transplant With Bortezomib as GVHD Prophylaxis in High Risk Multiple Myeloma [NCT01954784] | Phase 1 | 8 participants (Actual) | Interventional | 2013-10-07 | Terminated(stopped due to Funding unavailable) |
| Phase II Study Evaluating the Efficacy of Lenalidomide in Association With Rituximab in Refractory or Relapse of Primary Central Nervous System Lymphoma (PCNSL) [NCT01956695] | Phase 2 | 45 participants (Actual) | Interventional | 2013-09-18 | Completed |
| MCLENA-2: A Phase II Clinical Trial for the Assessment of Biomarker Trajectory in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease Treated With Lenalidomide (Amendment to IND # 142121) [NCT06177028] | Phase 2 | 45 participants (Anticipated) | Interventional | 2024-01-02 | Not yet recruiting |
| A Prospective Phase II Study of Polatuzumab, Rituximab, and Lenalidomide(Pola-R2) in Newly-diagnosed Non-fit Elderly DLBCL Patients [NCT06176729] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-10-24 | Recruiting |
| A Phase 3, Two-stage, Randomized, Multi-center, Controlled, Open-label Study Comparing Iberdomide Maintenance to Lenalidomide Maintenance Therapy After Autologous Stem Cell Transplantation (ASCT) in Participants With Newly Diagnosed Multiple Myeloma (NDMM [NCT05827016] | Phase 3 | 1,216 participants (Anticipated) | Interventional | 2023-06-22 | Recruiting |
| A Phase I Open Label Study Of Panobinostat In Combination With Lenalidomide, Bortezomib, And Dexamethasone In Patients With Relapsed And Relapsed/Refractory Multiple Myeloma [NCT01965353] | Phase 1 | 21 participants (Actual) | Interventional | 2013-10-31 | Completed |
| Phase II Study of Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma [NCT04151667] | Phase 2 | 33 participants (Actual) | Interventional | 2019-11-22 | Active, not recruiting |
| A Personalized Vaccine for the Immune Prevention of Multiple Myeloma [NCT03631043] | Early Phase 1 | 30 participants (Actual) | Interventional | 2018-12-21 | Active, not recruiting |
| A Phase I Trial of Lenalidomide, Umbralisib and Ublituximab in Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma [NCT04635683] | Phase 1 | 0 participants (Actual) | Interventional | 2022-09-30 | Withdrawn(stopped due to Investigational Drug removed from the market) |
| Phase I Trial of Daily Lenalidomide (CC-5013, Revlimid™) and Docetaxel Given Every Three Weeks in Patients With Advanced Solid Tumors [NCT00253344] | Phase 1 | 33 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Phase II Trial of Combination of Ixazomib and Lenalidomide and Dexamethasone in Smoldering Multiple Myeloma [NCT02916771] | Phase 2 | 55 participants (Actual) | Interventional | 2016-10-31 | Active, not recruiting |
| A Pilot Study of Lenalidomide Maintenance Therapy in Stage IIIB/IV Non-small Cell Lung Cancer After First-line Chemotherapy [NCT02018523] | Phase 1 | 7 participants (Actual) | Interventional | 2014-06-30 | Terminated(stopped due to Study did not enroll enough subjects to make a statistically sound conclusion.) |
| Phase 2, Open-Label Randomized Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone vs Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma [NCT04268498] | Phase 2 | 306 participants (Anticipated) | Interventional | 2020-02-11 | Recruiting |
| Phase I/II Trial of AT-101 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Symptomatic Multiple Myeloma [NCT02697344] | Phase 1 | 10 participants (Actual) | Interventional | 2016-04-14 | Completed |
| Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma [NCT03269669] | Phase 2 | 95 participants (Anticipated) | Interventional | 2018-01-23 | Recruiting |
| A Phase II Trial of Combination of Oral Lenalidomide and Low-dose Cyclophosphamide for Patients With Antibiotics-unresponsive Extranodal Marginal Zone B-cell Lymphoma [NCT04604028] | Phase 2 | 21 participants (Anticipated) | Interventional | 2020-11-10 | Not yet recruiting |
| A Phase I/II Trial Of Very Low to Low-Doses of Continuous Azacitidine in Combination With Standard Doses of Lenalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01155583] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2010-06-30 | Completed |
| Lenalidomide Combined With Rituximab as Front-line Therapy in Elderly Patients Aged Over 80 Years With Diffuse Large B Cell Lymphoma [NCT04622579] | Phase 2 | 20 participants (Anticipated) | Interventional | 2020-10-23 | Recruiting |
| A Phase I Dose Escalating Study of Bortezomib and Lenalidomide in Patients With Untreated or Previously Treated, Primary and Secondary Non 5q- Del Myelodysplasia [NCT00580242] | Phase 1 | 23 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Phase II Study of Cetuximab and Lenalidomide in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT01133665] | Phase 2 | 42 participants (Actual) | Interventional | 2010-02-28 | Completed |
| A Phase II Clinical Trial of Lenalidomide and Prednisone in Low and Intermediate-1 IPSS Risk, Non-del (5q) MDS Patients [NCT01133275] | Phase 2 | 28 participants (Actual) | Interventional | 2010-04-28 | Completed |
| A Phase II, Multicenter, Single-Arm, Open-Label Study To Evaluate The Safety And Efficacy Of Single-Agent Lenalidomide (Revlimid®, CC-5013) In Subjects With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma [NCT00179660] | Phase 2 | 50 participants (Actual) | Interventional | 2005-08-31 | Completed |
| A Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Lenalidomide (Revlimid ®) in Combination With Dexamethasone in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [NCT00474188] | Phase 2 | 26 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Business decision) |
| A Phase I Study to Investigate the Safety and Clinical Activity of Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 mAb in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell [NCT01088048] | Phase 1 | 241 participants (Actual) | Interventional | 2010-03-25 | Completed |
| A Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of Single-Agent Lenalidomide (Revlimid®, CC-5013) in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma [NCT00179673] | Phase 2 | 43 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Phase I/II Trial of Melphalan, Prednisone Plus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Stem Cell Transplant [NCT00477750] | Phase 1/Phase 2 | 33 participants (Actual) | Interventional | 2005-06-30 | Completed |
| A Phase II Study of the Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib, and Dexamethasone Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma [NCT02219178] | Phase 2 | 42 participants (Actual) | Interventional | 2014-11-30 | Completed |
| Phase II Study of Subcutaneous (SC) Bortezomib, Lenalidomide and Dexamethasone for Relapsed and/or Refractory Multiple Myeloma; Followed by SC Bortezomib Maintenance [NCT01647165] | Phase 2 | 0 participants (Actual) | Interventional | 2012-07-11 | Withdrawn |
| A Phase Ib, Multi-center, Open-label Dose Escalation and Expansion Platform Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma (NHL) [NCT04903197] | Phase 1 | 124 participants (Anticipated) | Interventional | 2022-01-24 | Recruiting |
| B- PRISM (Precision Intervention Smoldering Myeloma): A Phase II Trial of Combination of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma [NCT04775550] | Phase 2 | 60 participants (Anticipated) | Interventional | 2021-03-08 | Recruiting |
| A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus MLN9708 or Physicians Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis [NCT01659658] | Phase 3 | 177 participants (Actual) | Interventional | 2012-12-12 | Terminated(stopped due to Sponsor's decision) |
| Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide [NCT01604031] | Phase 1 | 2 participants (Actual) | Interventional | 2013-02-28 | Terminated |
| A Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma [NCT01335399] | Phase 3 | 748 participants (Actual) | Interventional | 2011-08-04 | Completed |
| The Safety, Tolerability and Preliminary Efficacy of PD-L1 Monoclonal Antibody Combined With Lenalidomide in Third-line Post-Treatment of Patients With Microsatellite Stable Advanced Colorectal Cancer: A Phase I Clinical Study [NCT04326296] | Phase 1 | 33 participants (Anticipated) | Interventional | 2020-05-30 | Not yet recruiting |
| A Phase I/II Clinical Trial of the mTor Inhibitor RAD001 (Everolimus) in Combination With Lenalidomide (Revlimid) for Patients With Relapsed or Refractory Lymphoid Malignancy [NCT01075321] | Phase 1/Phase 2 | 58 participants (Actual) | Interventional | 2011-01-10 | Completed |
| The Combination of Lenalidomide and Dexamethasone With or Without Intensification by High-dose Melphalan in the Treatment of Multiple Myeloma [NCT01090089] | Phase 3 | 348 participants (Actual) | Interventional | 2010-03-01 | Completed |
| A Phase 1, Multi-center, Open-label Study of the Safety and Efficacy of a Stepwise Dose-escalation Schedule of Lenalidomide Monotherapy in Subjects With Relapsed or Refractory B-cell Chronic Lymphocytic Leukemia [NCT00419250] | Phase 1 | 52 participants (Actual) | Interventional | 2006-12-01 | Completed |
| A Phase 1/2 Trial of Durvalumab (MEDI4736) When Given as a Single Agent or in Combination With Lenalidomide in Patients With Relapsed/ Refractory Peripheral T-cell Lymphoma, Including Cutaneous T-cell Lymphoma [NCT03011814] | Phase 1/Phase 2 | 62 participants (Anticipated) | Interventional | 2017-03-08 | Recruiting |
| Phase Ib/IIa Study of Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas [NCT02341014] | Phase 1/Phase 2 | 31 participants (Anticipated) | Interventional | 2015-01-02 | Completed |
| Lenalidomide and Low Dose Dexamethasone Induction Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy for Newly Diagnosed High-risk Multiple Myeloma [NCT00691704] | Phase 2 | 18 participants (Actual) | Interventional | 2008-08-31 | Completed |
| Phase II, Open-Label Study Evaluating Efficacy of Tafasitamab and Lenalinomide Associated to Rituximab in Frontline Diffuse Large B-Cell Lymphoma Patients of 80 y/o or Older [NCT04974216] | Phase 2 | 71 participants (Anticipated) | Interventional | 2021-12-20 | Recruiting |
| A Prospective Multicenter Pilot Trial to Evaluate the Efficacy of a Treatment With Fludarabine, Cyclophosphamide, Lenalidomide (FCL) for Advanced Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) Patients. [NCT00727415] | Phase 1/Phase 2 | 42 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A Modular Phase I-II Trial of Lenalidomide and Paclitaxel in Men With Castration-Resistant Prostate Cancer and Lymph-Node Dominant Metastases [NCT00933426] | Phase 1 | 17 participants (Actual) | Interventional | 2009-08-31 | Terminated(stopped due to Terminated early due to slow accrual as Phase I dose escalation study.) |
| Consolidation Therapy With Lenalidomide (Revlimid®) With or Without Rituximab Followed by Maintenance Therapy With Revlimid® After Autologous/Syngeneic Transplant for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma [NCT00833534] | Phase 2 | 0 participants (Actual) | Interventional | 2009-02-28 | Withdrawn(stopped due to No patient enrolled on study. Did not get patients in timely fashion. All referrals for study when assessed were not eligible.) |
| Lenalidomide Combined With R-CHOP in Newly Diagnosed Double-expressor Diffuse Large B-Cell Lymphoma Patients [NCT04164368] | Phase 2 | 62 participants (Anticipated) | Interventional | 2019-10-22 | Recruiting |
| Quality of Life, Symptoms and Treatment Satisfaction in Adult Patients With Relapsed and/or Refractory Multiple Myeloma, Receiving Ixazomib (Ninlaro®) in Combination With Lenalidomide and Dexamethasone in a Real World Setting: Pilot Study [NCT03903406] | | 40 participants (Anticipated) | Observational | 2019-05-31 | Not yet recruiting |
| Treatment With Lenalidomide, Bendamustine and Prednisone (RBP) in Patients With Relapsed or Refractory Multiple Myeloma After Autologous Stem Cell Transplantation or Conventional Chemotherapy OSHO #077 [NCT01002703] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2009-09-30 | Recruiting |
| A Phase I Trial Using Cyclophosphamide, Rituximab and Revlimid (CR2) for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL) and SLL [NCT01005979] | Phase 1 | 6 participants (Actual) | Interventional | 2010-07-31 | Terminated(stopped due to Slow Accrual) |
| Vorinostat (SAHA) and Lenalidomide After Autologous Transplant for Patients With Multiple Myeloma [NCT00729118] | Phase 1 | 19 participants (Actual) | Interventional | 2008-09-26 | Completed |
| Phase III Randomised Trial of Immunomodulatory Therapy in High Risk Solitary Bone Plasmacytoma [NCT02544308] | Phase 3 | 36 participants (Actual) | Interventional | 2017-03-10 | Active, not recruiting |
| Tafasitamab, Lenalidomide and Venetoclax Combination Therapy for Relapsed or Refractory Mantle Cell Lymphoma (V-MIND): A Phase II Study With Safety Lead-In [NCT05910801] | Phase 2 | 100 participants (Anticipated) | Interventional | 2023-12-29 | Not yet recruiting |
| Efficacy and Safety of Epcoritamab Monotherapy and in Combination With Lenalidomide as First-line Therapy for Anthracycline-ineligible Diffuse Large B-Cell Lymphoma Patients, an Open-label, Randomized, Multicenter, Global Phase 2 Trial [NCT05660967] | Phase 2 | 180 participants (Anticipated) | Interventional | 2023-03-06 | Recruiting |
| A Phase 2 Study Evaluating the Efficacy of Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma [NCT01121757] | Phase 2 | 11 participants (Actual) | Interventional | 2010-04-30 | Terminated(stopped due to The study closed temporarily in February 2012 pending analysis of samples collected. In October, 2012, Celgene requested closure of the study.) |
| A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients With Relapsed/Refractory Multiple Myeloma [NCT01160484] | Phase 2 | 40 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Study Of Pgv001 A Multi-Peptide Therapeutic Vaccine Platform For Use In The Treatment Of Malignancies In The Adjuvant Setting [NCT02721043] | Phase 1 | 13 participants (Actual) | Interventional | 2016-04-30 | Completed |
| An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of Ixazomib (MLN9708), a Second-Generation Proteasome Inhibitor, Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Re [NCT01217957] | Phase 1/Phase 2 | 65 participants (Actual) | Interventional | 2010-11-22 | Completed |
| Phase I/II Trial of Cediranib Alone or Cediranib and Lenalidomide in Iodine 131-Refractory Differentiated Thyroid Cancer [NCT01208051] | Phase 1/Phase 2 | 127 participants (Actual) | Interventional | 2010-09-09 | Completed |
| Frailty Score-guided Dosing of Lenalidomide, Dexamethasone and Daratumumab Induction Therapy in Elderly, Frail Newly Diagnosed Myeloma (MMY2035) [NCT04223661] | Phase 2 | 0 participants (Actual) | Interventional | 2021-12-06 | Withdrawn(stopped due to lack of funding) |
| Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy as Induction Followed by Bortezomib and Lenalidomide Maintenance in Patients With Newly Diagnosed High Risk Multiple Myeloma [NCT03641456] | Phase 2 | 50 participants (Anticipated) | Interventional | 2020-09-25 | Recruiting |
| A Phase 2/3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Lenalidomide (Revlimid ®) Versus Investigator's Choice in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma [NCT01197560] | Phase 2/Phase 3 | 111 participants (Actual) | Interventional | 2010-09-02 | Completed |
| Treatment of IgG4-Related Disease With Revlimid and Rituximab: The TIGR2 Trial [NCT02705638] | Phase 1 | 6 participants (Actual) | Interventional | 2016-04-30 | Completed |
| A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination With Melphalan and Dexamethasone in Subjects With Newly-diagnosed Light-chain (AL)-Amyloidosis [NCT00621400] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas [NCT01076543] | Phase 1/Phase 2 | 110 participants (Actual) | Interventional | 2010-04-15 | Completed |
| Nonmyeloablative Stem Cell Transplantation With or Without Lenalidomide for Chronic Lymphocytic Leukemia (RV-CLL-PI-0294) [NCT00899431] | Phase 2 | 39 participants (Actual) | Interventional | 2009-05-06 | Terminated(stopped due to Terminated per PI's request at the time of continuing review) |
| A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia [NCT00890929] | Phase 1/Phase 2 | 45 participants (Actual) | Interventional | 2009-04-30 | Completed |
| Revlimid® Capsules Drug Use-results Surveillance Relapsed or Refractory Adult T-cell Leukemia Lymphoma [NCT03098589] | | 80 participants (Anticipated) | Observational | 2017-05-30 | Recruiting |
| Phase I-II Study of Carfilzomib, Lenalidomide, Dexamethasone, and Panobinostat, Ca-R-Pa-Diem, as Induction Therapy for Newly Diagnosed, Untreated, Transplant-Eligible, Multiple Myeloma Patients [NCT02802163] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2017-06-30 | Withdrawn(stopped due to study drug unavailable) |
| Lenalidomide in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma(CLL/SLL): a Phase I Study [NCT01400685] | Phase 1 | 34 participants (Anticipated) | Interventional | 2012-12-31 | Completed |
| A Phase 1/2 Study of Lenalidomide in Combination With Bendamustine (LEBEN) in Relapsed and Primary Refractory Hodgkin Lymphoma [NCT01412307] | Phase 1/Phase 2 | 36 participants (Anticipated) | Interventional | 2011-07-31 | Active, not recruiting |
| Relevance of Maintenance Therapy Using Lenalidomide (Revimid®) After Autologous Stem Cell Transplantation Patients Under the Age Of 65. (Open, Randomised, Multi-centric Trial Versus Placebo). [NCT00430365] | Phase 3 | 614 participants (Anticipated) | Interventional | 2006-06-30 | Completed |
| Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma [NCT01421927] | Phase 1 | 13 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A Pilot/Feasibility Phase I Study of Bendamustine, Rituximab and Lenalidomide in Patients With Refractory/Relapsed Indolent NHL [NCT01429025] | Phase 1 | 26 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A Multidose Phase I Study of Oral CC5013, a Thalidomide Derivative, in Patients With Refractory Metastatic Cancer [NCT00031941] | Phase 1 | 0 participants | Interventional | 2002-04-30 | Completed |
| Evaluation of Lenalidomide as Maintenance Therapy Post Allogeneic Hematopoietic Cell Transplantation for High-risk Multiple Myeloma [NCT00847639] | Phase 2 | 30 participants (Actual) | Interventional | 2009-02-28 | Completed |
| A Phase 1 Study of Mosunetuzumab With Polatuzumab Vedotin and Lenalidomide (M+Pola+Len) in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) [NCT06015880] | Phase 1 | 30 participants (Anticipated) | Interventional | 2024-09-03 | Recruiting |
| Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a Non-Randomized Single Arm US Extension of Mosunetuzumab [NCT04712097] | Phase 3 | 474 participants (Anticipated) | Interventional | 2021-10-27 | Recruiting |
| A Phase II, Open-label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Allogeneic Stem Cell Transplant [NCT03413800] | Phase 2 | 10 participants (Actual) | Interventional | 2018-02-12 | Active, not recruiting |
| Daratumumab Versus Lenalidomide Maintenance Therapy for Multiple Myeloma: A Randomized Pilot Study Comparing Patient-Reported Health Related Quality of Life Measures With a Plant Based Nutrition Intervention Sub Study (NUTRIVENTION-4) [NCT04497961] | Phase 2 | 100 participants (Anticipated) | Interventional | 2020-08-28 | Recruiting |
| A Phase I Study of DVd +/ CC-5013 in Relapsed Refractory Multiple Myeloma (MM) [NCT00091624] | Phase 1 | 77 participants (Actual) | Interventional | 2003-03-31 | Completed |
| UARK 2003-35, A Phase III Study of Bortezomib Versus Bortezomib in Two Doses in Combination With Revlimid™ for Patients Relapsing or Progressing on Total Therapy II (UARK 98-026) [NCT00093028] | Phase 3 | 315 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Evaluation of Ixazomib, Lenalidomide, Dexamethasone Induction and Extended Consolidation Followed by Lenalidomide Maintenance in Newly Diagnosed Multiple Myeloma Patients ≤65 Years Eligible for High Dose Therapy [NCT02897830] | Phase 2 | 46 participants (Actual) | Interventional | 2016-08-05 | Terminated(stopped due to negatives results) |
| Phase I/II Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose And To Evaluate The Safety Profile of Lenalidomide (Revlimid®) With Topotecan In Subjects With Advanced Ovarian and Primary Peritoneal Carcinoma [NCT00179712] | Phase 1/Phase 2 | 60 participants | Interventional | 2005-04-30 | Completed |
| A Phase I/II Study Of Lenalidomide (Revlimid ) In Combination With Gemcitabine In Patients With Untreated Advanced Carcinoma Of The Pancreas [NCT00179751] | Phase 1/Phase 2 | 50 participants | Interventional | 2005-04-30 | Terminated |
| A Multicenter, Phase I Study to Determine the Maximum Tolerated Dose, Safety, Pharmacokinetics and Efficacy of Lenalidomide With and Without Dexamethasone in Japanese Subjects With Previously Treated Multiple Myeloma [NCT00555100] | Phase 1 | 15 participants (Actual) | Interventional | 2007-07-01 | Completed |
| A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma [NCT05714839] | Phase 1 | 124 participants (Anticipated) | Interventional | 2023-06-14 | Recruiting |
| A Phase 3, Open-Label Study to Evaluate Safety and Efficacy of Epcoritamab in Combination With Rituximab and Lenalidomide (R2) Compared to R2 in Subjects With Relapsed or Refractory Follicular Lymphoma (EPCORE FL-1) [NCT05409066] | Phase 3 | 500 participants (Anticipated) | Interventional | 2022-09-20 | Recruiting |
| Phase I Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose And To Evaluate The Safety Profile Of Lenalidomide (Revlimid®, CC-5013) With Pemetrexed In Subjects With Advanced Non-Small Cell Lung Cancer [NCT00179699] | Phase 1 | 40 participants | Interventional | 2005-09-30 | Terminated |
| A Multicenter, Single-Arm, Open-Label, Study To Evaluate The Safety And Efficacy Of Single-Agent Lenalidomide (Revlimid®) In Subjects With Androgen Independent Prostate Cancer [NCT00179738] | Phase 2 | 40 participants | Interventional | 2005-04-30 | Terminated |
| A Phase II Study of Clarithromycin (Biaxin), Lenalidomide (Revlimid), and Dexamethasone (Decadron) for Newly Diagnosed Subjects With Multiple Myeloma [NCT00151203] | Phase 2 | 50 participants (Anticipated) | Interventional | 2004-12-31 | Completed |
| A Phase II Trial of CC-5013 in Patients With Primary Systemic Amyloidosis [NCT00166413] | Phase 2 | 38 participants (Anticipated) | Interventional | 2005-04-30 | Completed |
| Phase I Safety Study of the Combination of Lenalidomide and Dacarbazine (DTIC) in Patients With Metastatic Malignant Melanoma Previously Untreated With Systemic Chemotherapy (CC-5013-MEL-003) [NCT00412581] | Phase 1 | 28 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Phase I, Open-Label, Multi-Center Study of CKD-581 in Combination With Lenalidomide and Dexamethasone in Patients With Previously Treated Multiple Myeloma [NCT03150316] | Phase 1 | 18 participants (Anticipated) | Interventional | 2017-05-10 | Recruiting |
| Evaluation of Ruxolitinib and Lenalidomide Combination as a Therapy for Patients With Myelofibrosis [NCT01375140] | Phase 2 | 31 participants (Actual) | Interventional | 2011-09-22 | Completed |
| Pilot Study of Lenalidomide and Dexamethasone in Combination With MEDI-551 in Previously Untreated Multiple Myeloma. [NCT01861340] | Early Phase 1 | 20 participants (Actual) | Interventional | 2014-05-31 | Completed |
| Phase I/II Study of Venetoclax or Lenalidomide in Combination With Ublituximab and Umbralisib in Subjects With Relapsed or Refractory CLL/SLL and NHL [NCT03379051] | Phase 1/Phase 2 | 78 participants (Actual) | Interventional | 2018-03-27 | Terminated(stopped due to Strategic/Business Decision) |
| A Randomized Phase II, 2-armed Study in Transplant Ineligible (TI) Patients With Newly Diagnosed Multiple Myeloma (NDMM) Comparing Carfilzomib + Thalidomide + Dexamethasone (KTd) Versus Carfilzomib + Lenalidomide + Dexamethasone (KRd) Induction Therapy Wi [NCT02891811] | Phase 2 | 124 participants (Actual) | Interventional | 2017-03-10 | Active, not recruiting |
| A PHASE IB STUDY OF THE BTKi CC-292 COMBINED WITH LENALIDOMIDE IN ADULTS PATIENTS WITH RELAPSED/REFRACTORY B-CELL LYMPHOMA [NCT01766583] | Phase 1 | 18 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Phase II Trial of Ibrutinib, Lenalidomide and Rituximab for Patients With Relapsed/Refractory Mantle Cell Lymphoma [NCT02460276] | Phase 2 | 50 participants (Actual) | Interventional | 2015-04-30 | Completed |
| Double-blind Randomized Controlled Clinical Trial of Low-dose Lenalidomide in the Treatment of COVID-19 Disease [NCT04361643] | Phase 4 | 120 participants (Anticipated) | Interventional | 2020-10-27 | Not yet recruiting |
| A Phase I Dose Escalation Study of Autologous Expanded Natural Killer (NK) Cells for Immunotherapy of Relapsed Refractory Neuroblastoma With Dinutuximab +/- Lenalidomide [NCT02573896] | Phase 1 | 13 participants (Actual) | Interventional | 2019-01-14 | Active, not recruiting |
| A Phase II Clinical Trial of Lenalidomide Intensification in Patients With Serologic/Asymptomatic Progression of Multiple Myeloma While on Lenalidomide Maintenance [NCT01463670] | Phase 2 | 11 participants (Actual) | Interventional | 2011-10-28 | Completed |
| Phase I/II Study of Lenalidomide Maintenance Following BEAM (+/- Rituximab) for Chemo-Resistant or High Risk Non-Hodgkin?s Lymphoma [NCT01035463] | Phase 1/Phase 2 | 74 participants (Actual) | Interventional | 2009-11-12 | Completed |
| Phase II Study of Lenalidomide for the Treatment of Relapsed or Refractory Hodgkin's Lymphoma [NCT00478959] | Phase 2 | 30 participants (Actual) | Interventional | 2006-12-31 | Completed |
| QUIREDEX: A National, Open-Label, Multicenter, Randomized, Phase III Study of Revlimid (Lenalidomide) and Dexamethasone (ReDex) Treatment Versus Observation in Patients With Smoldering Multiple Myeloma With High Risk of Progression [NCT00480363] | Phase 3 | 120 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Phase I Study of Lenalidomide in Acute Leukemias and Chronic Lymphocytic Leukemia. [NCT00466895] | Phase 1 | 37 participants (Actual) | Interventional | 2007-04-30 | Completed |
| Multicenter, Randomized, Double-blind, Placebo-controlled Study to Compare the Efficacy and Safety of CC-5013 vs. Placebo in Subjects With Metastatic Malignant Melanoma Whose Disease Has Progressed on Treatment With DTIC, IL-2, or IFN Based Therapy [NCT00057616] | Phase 3 | 274 participants | Interventional | 2002-10-01 | Completed |
| Open Label Multi-center Pilot Phase I/II Non-controlled Clinical Trial to Assess Safety and Efficieecy of the Lenalidomide and Dexamethasone Association in Patients With Chronic Relapse or Treatment Resistant Lymphatic Leukemia Following Treatment Contain [NCT01246557] | Phase 1/Phase 2 | 20 participants (Anticipated) | Interventional | 2009-12-31 | Completed |
| Phase I Trial of Cytarabine and Lenalidomide in Relapsed or Refractory Acute Myeloid Leukemia Patients [NCT01246622] | Phase 1 | 32 participants (Actual) | Interventional | 2011-02-07 | Completed |
| A Phase I Combination Trial of SGN-33 (Anti-huCD33 mAb; HuM195; Lintuzumab) and Lenalidomide (Revlimid®) in Patients With Myelodysplastic Syndromes (MDS) [NCT00502112] | Phase 1 | 13 participants (Actual) | Interventional | 2008-03-31 | Completed |
| A Phase II, Single Arm Study Examining the Combination of Revlimid (Lenalidomide) and Vidaza (Azacitidine) (RA-CLL) for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) [NCT01241786] | Phase 2 | 5 participants (Actual) | Interventional | 2010-07-31 | Terminated(stopped due to The study was closed early due to poor accrual) |
| Randomized, Open Label, Multicenter Phase III Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 Tablets Versus Best Available Care (The RESPONSE Trial) [NCT01243944] | Phase 3 | 222 participants (Actual) | Interventional | 2010-10-27 | Completed |
| A Phase II Trial to Determine the Effect of Imetelstat (GRN163L) on Patients With Previously Treated Multiple Myeloma [NCT01242930] | Phase 2 | 13 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Phase I Study of SGN-40 (Anti-huCD40 mAb), Lenalidomide (Revlimid®, cc 5013), and Dexamethasone in Patients With Multiple Myeloma (MM) [NCT00525447] | Phase 1 | 36 participants (Actual) | Interventional | 2007-08-31 | Completed |
| Phenotypic Personalized Medicine: Systematically Optimized Combination Therapy in Multiple Myeloma Using CURATE.AI [NCT03759093] | Phase 2/Phase 3 | 20 participants (Anticipated) | Interventional | 2023-09-10 | Recruiting |
| A Phase 1b Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone (DRd) in Japanese Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation [NCT02918331] | Phase 1 | 7 participants (Actual) | Interventional | 2016-09-30 | Completed |
| A Phase I/II Study of Lenalidomide and Obinutuzumab With CHOP for Diffuse Large B Cell Lymphoma [NCT02529852] | Phase 1/Phase 2 | 59 participants (Actual) | Interventional | 2015-11-04 | Completed |
| A Phase Ib/III Study to Evaluating the Efficacy and Safety of Parsaclisib in Combination With Rituximab and Lenalidomide Versus Rituximab in Combination With Lenalidomide in Subjects With Relapsed or Refractory Follicular Lymphoma [NCT05867030] | Phase 1 | 0 participants (Actual) | Interventional | 2023-07-28 | Withdrawn(stopped due to Development strategy adjustment) |
| Prospective, Single-arm, Phase II Clinical Study of Rituximab, Lenalidomide, and Zanubrutinib Combination Regimen Followed by Immunochemotherapy in the Treatment of Elderly Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma [NCT05290090] | Phase 2 | 31 participants (Anticipated) | Interventional | 2021-10-01 | Recruiting |
| A Phase I Dose Escalation Study of Lenalidomide (Revlimid) in Combination With Fludarabine-Rituximab (Rituxan) for Previously Untreated CLL/SLL [NCT00543114] | Phase 1 | 9 participants (Actual) | Interventional | 2007-10-31 | Terminated(stopped due to lack of efficacy and tolerability) |
| Phase II Study of Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non Hodgkin's Lymphoma [NCT01316523] | Phase 2 | 30 participants (Actual) | Interventional | 2010-12-31 | Active, not recruiting |
| A Phase II Trial of the Combination of Lenalidomide and Rituximab in Patients With Relapsed/Refractory Follicular NHL (RV 0163) [NCT00848328] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-08-25 | Active, not recruiting |
| Natural Killer Cells in Allogeneic Cord Blood Transplantation [NCT01619761] | Phase 1 | 13 participants (Actual) | Interventional | 2013-05-03 | Active, not recruiting |
| Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q: a Multicenter, Randomized, Double-blind, Placebo Controlled Study - QOL-ONE Rev2MDS [NCT02928419] | Phase 2 | 2 participants (Actual) | Interventional | 2015-05-31 | Terminated(stopped due to "the study has been closed due to a low rate of patient enrollment (2 patients since the start of the trial)") |
| Lenalidomide Following Rituximab and Fludarabine in Untreated Chronic Lymphocytic Leukemia [NCT00860457] | Phase 2 | 22 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Bortezomib-lenalidomide-dexamethasone Combined With Radiotherapy for Newly Diagnosed Solitary Plasmacytoma [NCT05248633] | Phase 2 | 220 participants (Anticipated) | Interventional | 2022-04-21 | Recruiting |
| A Phase 2, Multi-Center, Randomized, Double-Blinded, Parallel Group Study of the Safety and Efficacy of Different Lenalidomide (REVLIMID®) Dose Regimens in Subjects With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia [NCT00963105] | Phase 2 | 104 participants (Actual) | Interventional | 2009-10-19 | Completed |
| A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) vs VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Previously Untreated Multiple Myeloma Who Are Eligible for High-dose Therapy [NCT03710603] | Phase 3 | 690 participants (Actual) | Interventional | 2018-12-14 | Active, not recruiting |
| A Phase II Study of Acalabrutinib, Lenalidomide, and Rituximab (aR2) in Patients With Previously Untreated Follicular Lymphoma [NCT04404088] | Phase 2 | 24 participants (Anticipated) | Interventional | 2020-07-16 | Recruiting |
| Phase 2 Trial of Pembrolizumab, Lenalidomide, and Dexamethasone for Initial Therapy of Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplantation [NCT02880228] | Phase 2 | 11 participants (Actual) | Interventional | 2016-09-16 | Completed |
| An Open-label, Pharmacokinetic Study of Lenalidomide (Revlimid) and High-dose Dexamethasone Induction Therapy in Previously Untreated Multiple Myeloma Patients With Various Degrees of Renal Dysfunction - Validation of Official Dosing Guidelines for Renal [NCT01270932] | Phase 2 | 28 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Phase I/II Study of Carfilzomib Plus Lenalidomide and Rituximab in the Treatment of Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma [NCT01729104] | Phase 1 | 18 participants (Actual) | Interventional | 2013-04-25 | Terminated(stopped due to Low response) |
| A Phase II Trial of Bortezomib (NSC #681239) + Lenalidomide (Revlimid™, CC-5013) (NSC #703813) for Relapsed/Refractory Mantle Cell Lymphoma [NCT00553644] | Phase 2 | 53 participants (Actual) | Interventional | 2007-11-15 | Completed |
| An Open-Label Phase II Study of the Safety and Efficacy of Doxorubicin and Cyclophosphamide in Combination With Bortezomib, Lenalidomide, and Dexamethasone for Treatment of Patients With Newly Diagnosed Multiple Myeloma [NCT01481194] | Phase 2 | 35 participants (Actual) | Interventional | 2011-11-30 | Completed |
| Phase II Trial of CC-5013 in Patients With Advanced Renal Cell Carcinoma With Either No Prior Treatment or One Prior Treatment Regimen [NCT00096525] | Phase 2 | 0 participants | Interventional | 2004-07-31 | Completed |
| A Multicenter, Open-label Study to Determine the Safety and Efficacy of Single-agent CC-5013 in Subjects With Relapsed and Refractory Multiple Myeloma [NCT00065351] | Phase 2 | 222 participants (Actual) | Interventional | 2003-07-01 | Completed |
| Administration of an Allogeneic Myeloma GM-CSF Vaccine in Conjunction With a Lenalidomide Containing Regimen in Myeloma Patients With Near Complete Remission [NCT01349569] | Phase 2 | 19 participants (Actual) | Interventional | 2012-01-31 | Completed |
| A Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Painful Lumbar Radiculopathy [NCT00120120] | Phase 2/Phase 3 | 181 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Phase II Trial of REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas [NCT00287287] | Phase 2 | 25 participants (Actual) | Interventional | 2006-02-28 | Completed |
| A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tafasitamab Plus Lenalidomide in Addition to Rituximab Versus Lenalidomide in Addition to Rituximab in Patients With Relapsed/Refractory (R/R [NCT04680052] | Phase 3 | 654 participants (Actual) | Interventional | 2021-04-15 | Active, not recruiting |
| A Phase 3 Randomized, Open Label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma [NCT04270409] | Phase 3 | 320 participants (Anticipated) | Interventional | 2020-06-16 | Recruiting |
| A Multicenter, Open Label, Phase Ib/II Study of Lenalidomide, Venetoclax and Obinutuzumab in Patients With Treatment-Naïve Follicular Lymphoma [NCT03980171] | Phase 1/Phase 2 | 61 participants (Anticipated) | Interventional | 2019-08-19 | Recruiting |
| LCI-HEM-MYE-KRdD-001: Phase II Study of Daratumumab Combined With Carfilzomib, Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma [NCT04113018] | Phase 2 | 39 participants (Actual) | Interventional | 2020-01-10 | Active, not recruiting |
| A Phase II Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) [NCT01199575] | Phase 2 | 30 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A Phase II Trial Addressing Feasibility and Activity of Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma [NCT03031483] | Phase 2 | 44 participants (Actual) | Interventional | 2017-04-03 | Active, not recruiting |
| Lenalidomide to Reverse Drug Resistance After Lenvatinib Combined With PD-1 Inhibitors in the First-line Treatment of Advanced HCC ：a Prospective, Exploratory, Single-arm, Open-label, Multi-center Clinical Study [NCT05831969] | Phase 2 | 23 participants (Anticipated) | Interventional | 2023-06-05 | Not yet recruiting |
| A Prospective, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Obinutuzumab(GA101) in Combination With Lenalidomide in Relapsed and Refractory(R/R) Marginal Zone Lymphoma (MZL) [NCT05846750] | Phase 2 | 59 participants (Anticipated) | Interventional | 2022-11-01 | Recruiting |
| A Phase II Study of Steroid Sparing Treatment With Daratumumab and Lenalidomide in Newly Diagnosed Transplant Ineligible Patients With Multiple Myeloma [NCT04635189] | Phase 2 | 28 participants (Anticipated) | Interventional | 2021-07-27 | Recruiting |
| A Phase II Study Evaluating the Efficacy/Safety of Lenalidomide With or Without Epoetin Beta in Transfusion-dependent ESA-resistant Patients With IPSS Low- and Intermediate-1 Risk Myelodysplastic Syndromes Without Chromosome 5 Abnormality. [NCT01718379] | Phase 2 | 132 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy [NCT01050790] | | 17 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Pilot Study of the Combination of Lenalidomide (Revlimid®) With Two Different Dose Levels of Short Term Administration of Recombinant Human Stem Cell Factor (rhSCF; Ancestim) for Myelodysplasia. [NCT00434239] | Early Phase 1 | 25 participants (Actual) | Interventional | 2007-02-28 | Active, not recruiting |
| A Phase I Trial of CC-5013 (Lenalidomide) in Pediatric Patients With Recurrent or Refractory Primary CNS Tumors [NCT00100880] | Phase 1 | 45 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Phase II Study of Response Adapted Therapy Using Single Agent Lenalidomide in Older Adults With Newly Diagnosed, Standard Risk Multiple Myeloma [NCT01054144] | Phase 2 | 27 participants (Actual) | Interventional | 2010-01-14 | Completed |
| A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma [NCT05556616] | Phase 1 | 120 participants (Anticipated) | Interventional | 2022-10-27 | Active, not recruiting |
| Phase II Combination Immunotherapy After ASCT for Advanced Myeloma to Study MAGE-A3 Immunizations With Hiltonol® (Poly-ICLC) Plus Transfer of Vaccine-Primed Autologous T Cells Followed by Lenalidomide Maintenance [NCT01245673] | Phase 2 | 28 participants (Actual) | Interventional | 2011-05-10 | Completed |
| An Open-Label Phase I Study of the Safety and Efficacy of Bortezomib in Combination With CC-5013 in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma [NCT00153933] | Phase 1 | 58 participants (Actual) | Interventional | 2004-08-31 | Completed |
| A Non-interventional, Observational Post-marketing Registry of Patients Treated With Revlimid (Lenalidomide) in Taiwan [NCT01752075] | | 100 participants (Actual) | Observational [Patient Registry] | 2011-01-01 | Completed |
| Sintilimab and Lenalidomide as a Treatment for CAEBV：a Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial [NCT04518982] | Phase 2 | 51 participants (Anticipated) | Interventional | 2020-08-01 | Recruiting |
| A Phase III Non-Inferiority Randomized Controlled Trial of Fixed Duration Versus Continuous Daratumumab Among Transplant Ineligible Older Adults With Newly Diagnosed Multiple Myeloma [NCT06182774] | Phase 3 | 559 participants (Anticipated) | Interventional | 2024-02-28 | Not yet recruiting |
| Randomized Phase II Study of the Addition of Targeted Therapeutic Agents to Tafasitamab-Based Therapy in Non-Transplant-Eligible Patients With Relapsed/Refractory Large B-Cell Lymphoma [NCT05890352] | Phase 2 | 227 participants (Anticipated) | Interventional | 2023-09-26 | Recruiting |
| A Phase 3 Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Follicular Lymphoma [NCT05371093] | Phase 3 | 230 participants (Anticipated) | Interventional | 2022-09-12 | Recruiting |
| A Dose Escalation and Expansion Study of ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma [NCT05259839] | Phase 1 | 270 participants (Anticipated) | Interventional | 2022-10-20 | Recruiting |
| Phase II Multicenter Trial of Anti-BCMA CAR T-Cell Therapy for MM Patients With Sub-Optimal Response After Auto HCT and Maintenance Len. BMTCTN1902 [NCT05032820] | Phase 2 | 40 participants (Anticipated) | Interventional | 2022-01-05 | Recruiting |
| Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma With or Without Vaccination With Dendritic Cell/Myeloma Fusions (BMT CTN 1401) [NCT02728102] | Phase 2 | 203 participants (Actual) | Interventional | 2016-07-31 | Completed |
| A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidom [NCT02600897] | Phase 1/Phase 2 | 114 participants (Actual) | Interventional | 2016-03-24 | Completed |
| A Phase I Study of Gemcitabine, Carboplatin and Lenalidomide (GCL) for Treatment of Patients With Advanced/Metastatic Urothelial Carcinoma (UC) and Other Solid Tumors [NCT01352962] | Phase 1 | 18 participants (Actual) | Interventional | 2011-09-26 | Completed |
| A Phase II Trial of Revlimid, Cyclophosphamide, and Dexamethasone in Patients With > Newly Diagnosed Active Multiple Myeloma [NCT00478218] | Phase 2 | 53 participants (Actual) | Interventional | 2006-07-31 | Completed |
| A Phase II Study of Dexamethasone (DECADRON®), Thalidomide (THALOMID®), and Lenalidomide (REVLIMID®) for Subjects With Relapsed or Refractory Multiple Myeloma [NCT00538824] | Phase 2 | 5 participants (Actual) | Interventional | 2007-12-31 | Terminated(stopped due to low enrollment) |
| A Phase II Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) by Applying Non-Host-Exhausting and Timely Dose-Reduced Mel-80-CFZ-TD-Pace Transplant(s) With Interspersed Mel-20-CFZ-TD-Pace With CFZ-RD and CFZ-D Ma [NCT02128230] | Phase 2 | 20 participants (Actual) | Interventional | 2014-06-10 | Terminated(stopped due to Low enrollment and Futility as determined by Amgen's Carfilzomib NASCR program.) |
| Phase Ib Dose Finding Study of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (MCL) [NCT02446236] | Phase 1 | 27 participants (Actual) | Interventional | 2015-06-18 | Active, not recruiting |
| A Phase II Study of Lenalidomide in Patients With Chronic Lymphocytic Leukemia Older Than 65 Years of Age [NCT01011894] | Phase 2 | 26 participants (Actual) | Interventional | 2009-11-06 | Completed |
| Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment w/ Carfilzomib, Lenalidomide (Revlimid®) and Dexamethasone (CRD) in Subjects w/ Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring Syst [NCT01029054] | Phase 1/Phase 2 | 53 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia [NCT01034592] | Phase 1 | 2 participants (Actual) | Interventional | 2009-11-30 | Terminated(stopped due to Poor accrual related to rarity of Diamond-Blackfan anemia (DBA)) |
| A Multicenter Prospective Phase II Study of Rituximab Combined, Lenalidomide, Dexamethasone Followed by Lenalidomide Maintenance in Patients With Newly Diagnosed Waldenström's Macroglobulinemia [NCT03697356] | Phase 2 | 54 participants (Anticipated) | Interventional | 2019-03-06 | Recruiting |
| A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma [NCT01460940] | Phase 2 | 24 participants (Actual) | Interventional | 2011-10-13 | Completed |
| A Phase 2 Study of Epcoritamab and Lenalidomide (E-Len) in Patients With Previously Untreated Follicular Lymphoma (FL) [NCT06112847] | Phase 2 | 27 participants (Anticipated) | Interventional | 2024-03-22 | Not yet recruiting |
| A Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Idecabtagene Vicleucel With Lenalidomide Maintenance Versus Lenalidomide Maintenance Therapy Alone in Adult Participants With Newly Diagnosed Multiple Myeloma Who Have Suboptima [NCT06045806] | Phase 3 | 618 participants (Anticipated) | Interventional | 2023-10-16 | Recruiting |
| Phase I Trial of Three-Weekly Docetaxel, Carboplatin and Oral CC-5013 in Patients With Advanced Solid Tumors [NCT00415116] | Phase 1 | 14 participants (Actual) | Interventional | 2004-08-31 | Completed |
| Combination Post-transplant Consolidation Therapy With Isatuximab, Lenalidomide, Dexamethasone (IsaRD) in Multiple Myeloma Patients With Persistent Marrow Minimal Residual Disease (Elimination of MRD After Transplant; E-MAT) [NCT05690984] | Phase 2 | 31 participants (Anticipated) | Interventional | 2023-06-26 | Recruiting |
| Lenalidomide Maintenance in Plasma Cell Myeloma [NCT02538198] | Phase 2 | 108 participants (Actual) | Interventional | 2015-08-31 | Active, not recruiting |
| A Multicenter, Randomized, Double-Blind, Placebo-Controlled,Parallel-Group Study to Evaluate the Safety and Efficacy of CC-5013 in the Treatment of Adolescents and Adults With Moderately Severe Crohn's Disease [NCT00446433] | Phase 2 | 90 participants | Interventional | 2002-03-31 | Completed |
| Phase II Trial of Low Dose Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (Rev-Lite) in Patients at High Risk for Myelosuppression [NCT00482261] | Phase 2 | 150 participants (Anticipated) | Interventional | 2007-06-30 | Active, not recruiting |
| A Multi-Arm Complete Phase 1 Trial of Valproic Acid-Based 2-Agent Oral Regimens for Patients With Advanced Solid Tumor [NCT00495872] | Phase 1 | 204 participants (Actual) | Interventional | 2007-06-30 | Completed |
| Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities [NCT00546897] | Phase 2 | 48 participants (Actual) | Interventional | 2007-02-28 | Completed |
| A Phase 2 Study of Lenalidomide and Low-dose Dexamethasone in Combination With Dalteparin in Previously Untreated Multiple Myeloma [NCT01518465] | Phase 2 | 13 participants (Actual) | Interventional | 2012-01-09 | Terminated(stopped due to Insufficient Accrual) |
| Combination of Lenalidomide and Obinutuzumab (GA101) in Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) [NCT02225275] | Phase 2 | 9 participants (Actual) | Interventional | 2016-03-31 | Terminated(stopped due to Due to slow accrual) |
| An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma [NCT02532257] | Phase 2 | 46 participants (Actual) | Interventional | 2016-04-11 | Completed |
| Phase II Study of the Combination of Elotuzumab With Lenalidomide as Maintenance Therapy Post Autologous Stem Cell Transplant in Patients With Multiple Myeloma [NCT02420860] | Phase 2 | 113 participants (Actual) | Interventional | 2015-04-14 | Active, not recruiting |
| A Randomized, Double-blind, Placebo-Controlled Phase II Trial of an Allogeneic Myeloma GM-CSF Vaccine With Lenalidomide in Multiple Myeloma Patients in Complete or Near Complete Remission [NCT03376477] | Phase 2 | 54 participants (Anticipated) | Interventional | 2019-09-23 | Active, not recruiting |
| Lenalidomide and Low Dose Dexamethasone Versus Bortezomib, Lenalidomide and Low Dose Dexamethasone for Induction, in Patients With Previously Untreated Multiple Myeloma [NCT01530594] | Phase 3 | 440 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma [NCT01537861] | Early Phase 1 | 7 participants (Actual) | Interventional | 2012-06-30 | Terminated(stopped due to Unexpected toxicity (2 early deaths)) |
| Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma [NCT01542918] | Phase 1 | 14 participants (Actual) | Interventional | 2012-12-17 | Completed |
| Lenalidomide as Second-line Treatment for Advanced Hepatocellular Carcinoma (HCC): a Phase II Clinical Trial [NCT01545804] | Phase 2 | 55 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A Pilot Study of Lenalidomide and Dexamethasone in Patients With Primary Plasma Cell Leukemia [NCT01553357] | Phase 2 | 23 participants (Actual) | Interventional | 2009-03-31 | Completed |
| STUDY OF THE EFFICACY AND SAFETY OF FIRST LINE TREATMENT WITH CHOP AND LENALIDOMIDE (Rev-CHOP) IN PATIENTS AGED FROM 60 TO 80 YEARS WITH PREVIOUSLY UNTREATED ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA (AITL) [NCT01553786] | Phase 2 | 80 participants (Actual) | Interventional | 2011-11-30 | Completed |
| Randomised Comparisons, in Myeloma Patients of All Ages, of Thalidomide, Lenalidomide, Carfilzomib and Bortezomib Induction Combinations, and of Lenalidomide and Combination Lenalidomide Vorinostat as Maintenance (Myeloma XI) [NCT01554852] | Phase 3 | 4,420 participants (Actual) | Interventional | 2010-05-31 | Active, not recruiting |
| A Multicentre Prospective Phase II Single Arm Trial Evaluating the Benefit of Therapy With Lenalidomide (Revlimid®) in Relapsed or Refractory Primary-cutaneous Large B-cell Lymphoma (Leg-type) After First Line Treatment by Chemotherapy Plus Rituximab for [NCT01556035] | Phase 2 | 19 participants (Actual) | Interventional | 2012-07-31 | Completed |
| A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q [NCT01556477] | Phase 2 | 72 participants (Anticipated) | Interventional | 2012-03-31 | Recruiting |
| Phase I Study of CC-5013 (Lenalidomide NSC# 703813) in Pediatric Patients With Relapsed/Refractory Solid Tumors or Myelodysplastic Syndrome [NCT00104962] | Phase 1 | 24 participants (Actual) | Interventional | 2005-03-31 | Completed |
| A Single-Center, Open-Label, Between-Patient, Dose-Escalation Phase 1 Study of CDC-501 In Patients With Solid Tumors [NCT00046735] | Phase 1 | 24 participants (Actual) | Interventional | 2002-06-01 | Completed |
| A Phase I Trial of CC-5013 (Lenalidomide) and CCI-779 in Patients With Relapsed or Refractory Multiple Myeloma [NCT00398515] | Phase 1 | 25 participants (Actual) | Interventional | 2007-03-31 | Completed |
| A Non-interventional, Post-authorization Safety Study of Patients With Relapsed or Refractory Mantle Cell Lymphoma to Further Investigate and Characterize the Association of Lenalidomide With Tumor Flare Reaction and High Tumor Burden [NCT03647124] | | 560 participants (Anticipated) | Observational | 2019-03-13 | Recruiting |
| Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated CLL With Four or Six Cycles of Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide Followed by Lenalidomide Consolidation/ Maintenance [NCT01723839] | Phase 2 | 21 participants (Actual) | Interventional | 2012-02-22 | Completed |
| A Multicenter, Open Label Study of Oral Melphalan, Prednisone, and CC-5013 (Revlimid) (MPR) as Induction Therapy in Elderly Newly Diagnosed Multiple Myeloma Patients [NCT00396045] | Phase 1/Phase 2 | 54 participants | Interventional | 2005-01-31 | Completed |
| A Phase I Trial Of A Thalidomide Analog, CC-5013, For The Treatment Of Patients With Recurrent High-Grade Gliomas [NCT00036894] | Phase 1 | 0 participants | Interventional | 2002-03-31 | Completed |
| A Phase Ib, Open-label, Randomized Study to Assess Safety and Preliminary Efficacy of Tafasitamab in Addition to R-CHOP or Tafasitamab Plus Lenalidomide in Addition to R-CHOP in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) - First-M [NCT04134936] | Phase 1 | 66 participants (Actual) | Interventional | 2019-12-11 | Completed |
| A Multicenter, Single-Arm, Open-Label Study of the Efficacy and Safety of CC-5013 Monotherapy in Subjects With Myelodysplastic Syndromes [NCT00064974] | Phase 2 | 215 participants (Actual) | Interventional | 2003-06-30 | Completed |
| A Multicenter, Open-Label Study to Evaluate the Preliminary Safety and Efficacy of CC-5013 in the Treatment of Complex Regional Pain Syndrome (CRPS) [NCT00067743] | Phase 2 | 40 participants (Actual) | Interventional | 2003-08-31 | Completed |
| A Phase II Multicenter Study of Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Therapy, Followed by High-dose Therapy With Melphalan and Autologous Peripheral Blood Stem Cell Transplantation, Consolidation With KRd, and Maintenance With Le [NCT02415413] | Phase 2 | 90 participants (Anticipated) | Interventional | 2015-05-31 | Active, not recruiting |
| A Phase II Study of Continuous Versus Syncopated Dosing of CC-5013 for the Treatment of Refractory Multiple Myeloma [NCT00051116] | Phase 2 | 100 participants (Actual) | Interventional | 2002-05-31 | Completed |
| A Phase II Open Label Study of the Safety and Efficacy of CC-5013 Treatment For Patients With Myelodysplastic Syndrome [NCT00044382] | Phase 2 | 25 participants | Interventional | 2002-02-01 | Completed |
| Multicenter, Randomized, Controlled, Double-Blind, Parallel-Group Study to Compare the Efficacy and Safety of Two CC-5013 Dose Regimens in Subjects With Metastatic Malignant Melanoma Whose Disease Has Progressed on Treatment With DTIC, IL-2 or IFN Based T [NCT00055562] | Phase 2/Phase 3 | 274 participants | Interventional | 2003-01-31 | Completed |
| A Phase I/II Trial Investigating the Combination of Pembrolizumab (Keytruda) With Cyclophosphamide and Lenalidomide for Patients With Relapsed Multiple Myeloma [NCT03191981] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2017-08-01 | Withdrawn(stopped due to Withdrawal of pharma support prior to opening to recruitment) |
| Phase I Safety Study of the Combination of Lenalidomide and DTIC (Dacarbazine) in Patients With Metastatic Malignant Melanoma Previously Untreated With Systemic Chemotherapy [NCT00179608] | Phase 1 | 28 participants | Interventional | 2005-09-01 | Completed |
| A Multicenter, Single-Arm, Open-Label, Study to Evaluate the Safety and Efficacy of Single-Agent Lenalidomide (Revlimid, CC-5013) in Subjects With Recurrent Non-Small Cell Lung Cancer [NCT00179686] | Phase 2 | 40 participants | Interventional | 2005-03-31 | Completed |
| Phase I/II Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose And To Evaluate The Safety Profile of Lenalidomide (Revlimid®) With Liposomal Doxorubicin In Subjects With Advanced Ovarian and Primary Peritoneal Carcinoma [NCT00179725] | Phase 1/Phase 2 | 60 participants | Interventional | 2005-11-30 | Terminated |
| PH Ib Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Normal Renal Function, Severe Renal Impairment, or End Stage Renal Disease Requiring Dialysis [NCT01393964] | Phase 1 | 35 participants (Actual) | Interventional | 2012-01-06 | Completed |
| A Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma [NCT01891643] | Phase 3 | 23 participants (Actual) | Interventional | 2013-09-30 | Terminated(stopped due to Insufficient enrollment) |
| A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS) [NCT00352001] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2006-05-31 | Completed |
| A Phase II Study of Combination Oral CC-5013 Lenalidomide (Revlimid™), Oral Sunitinib (Sutent™) and Low Dose Oral Metronomic Cyclophosphamide for the Treatment of Stage IV Ocular Melanoma [NCT00482911] | Phase 2 | 12 participants (Actual) | Interventional | 2007-04-30 | Terminated(stopped due to Investigator left the institute.) |
| A Phase II Study of Lenalidomide as Initial Treatment of Patients With Chronic Lymphocytic Leukemia Age 65 or Older. [NCT00535873] | Phase 2 | 61 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Phase I/II Study of Fludarabine, Rituximab, and Lenalidomide in Minimally Treated and Untreated Patients With Chronic Lymphocytic Leukemia [NCT00536341] | Phase 1/Phase 2 | 64 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase II Multicenter Study of Lenalidomide in Relapsed or Refractory Classical Hodgkin Lymphoma [NCT00540007] | Phase 2 | 80 participants (Actual) | Interventional | 2007-09-06 | Completed |
| A PHASE 1B/2, OPEN LABEL UMBRELLA STUDY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) CD3 BISPECIFIC ANTIBODY, IN COMBINATION WITH OTHER ANTI-CANCER TREATMENTS IN PARTICIPANTS WITH MULTIPLE MYELOMA [NCT05090566] | Phase 2 | 105 participants (Anticipated) | Interventional | 2021-10-27 | Recruiting |
| Phase 1b/2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma [NCT03223610] | Phase 1/Phase 2 | 145 participants (Anticipated) | Interventional | 2018-02-09 | Recruiting |
| Phase II Study of Lenalidomide and Rituximab for Patients With Relapsed and/or Refractory CD20+ Multiple Myeloma [NCT00567229] | Phase 2 | 3 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Lack of Accrual) |
| A Multicenter Study of Ibrutinib and Lenalidomide in Combination With DA-EPOCH-R in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma [NCT02142049] | Phase 1/Phase 2 | 35 participants (Actual) | Interventional | 2014-05-31 | Completed |
| A Phase II Study of Lenalidomide in Patients With Relapsed or Refractory HTLV-1 Associated Adult T Cell Leukemia/Lymphoma [NCT01274533] | Phase 2 | 4 participants (Actual) | Interventional | 2010-12-31 | Completed |
| DLCL002 Protocol for Young Patients With Newly Diagnosed High Risk Aggressive B-cell Lymphoma, a Multicenter Phase II Study [NCT03837873] | Phase 2 | 118 participants (Anticipated) | Interventional | 2019-01-21 | Recruiting |
| "A Phase II Trial of Revlimid® and On Demand Dexamethasone Dosing in Patients With Newly Diagnosed Symptomatic Multiple Myeloma" [NCT00772915] | Phase 2 | 39 participants (Actual) | Interventional | 2008-12-03 | Completed |
| A Pilot Open Label Study to Investigate the Effect of Cytotoxic Therapy and/or Radiotherapy Including Lenalidomide on Cancer Related Sleep Disturbances in Chronic Lymphocytic Leukemia (CLL) and Breast Cancer Patients Experiencing Clinically Significant Fa [NCT00792077] | Phase 2 | 6 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Phase II Study of Lenalidomide in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas [NCT00837031] | Phase 2 | 72 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Phase II Subcutaneous VELCADE and Oral Cyclophosphamide-based Induction + Sequential VELCADE and Revlimid Maintenance for Newly Diagnosed Multiple Myeloma in Non-transplant Candidates: An Entirely Non-intravenous Regimen [NCT01729338] | Phase 2 | 17 participants (Actual) | Interventional | 2012-12-19 | Terminated |
| Post-Transplant Maintenance Therapy With Isatuximab Plus Lenalidomide for High-Risk Multiple Myeloma Patients [NCT05776979] | Phase 2 | 61 participants (Anticipated) | Interventional | 2023-09-30 | Recruiting |
| A Phase II Study of Obinutuzumab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma [NCT02871219] | Phase 2 | 96 participants (Actual) | Interventional | 2016-12-06 | Active, not recruiting |
| A Phase 1b/2 Study of Selinexor (KPT-330) in Combination With Backbone Treatments for Relapsed/Refractory Multiple Myeloma and Newly Diagnosed Multiple Myeloma [NCT02343042] | Phase 1/Phase 2 | 518 participants (Actual) | Interventional | 2015-10-31 | Active, not recruiting |
| A Phase I/II Study of Lenalidomide and Obinutuzumab (GA101) in Relapsed Indolent Non-Hodgkin's Lymphoma [NCT01995669] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2014-05-21 | Completed |
| A Multicenter, Single-Arm, Open-Label, Expanded Access Program for Lenalidomide With or Without Dexamethasone in Previously Treated Subjects With Multiple Myeloma [NCT00179647] | Phase 3 | 1,913 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Multicenter, Single-Arm, Open-Label Expanded Access Program for Lenalidomide Plus Dexamethasone in Previously Treated Subjects With Multiple Myeloma [NCT00478777] | Phase 3 | 150 participants (Actual) | Interventional | 2007-03-31 | Completed |
| Lenalidomide Plus R-CHOP for CNS Relapse Prophylaxis in Diffuse Large B-cell Lymphoma [NCT04544059] | Phase 2 | 87 participants (Anticipated) | Interventional | 2020-10-01 | Not yet recruiting |
| E- PRISM: Precision Intervention Smoldering Myeloma: Phase II Trial of Combination of Elotuzumab, Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma [NCT02279394] | Phase 2 | 51 participants (Actual) | Interventional | 2014-12-11 | Completed |
| A Phase I Trial of Lenalidomide and Idelalisib in Recurrent Follicular Lymphoma [NCT01644799] | Phase 1 | 8 participants (Actual) | Interventional | 2013-07-31 | Completed |
| A Phase I Study of Lenalidomide Plus Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine for the Reinduction of Patients With Acute Myelogenous Leukemia [NCT01681537] | Phase 1 | 36 participants (Actual) | Interventional | 2012-09-30 | Completed |
| An Open-Label Phase I Study of the Safety of Perifosine in Combination With Lenalidomide and Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma [NCT00415064] | Phase 1 | 32 participants (Actual) | Interventional | 2006-12-31 | Completed |
| A Multicenter Phase I/II Trial Evaluating the Safety and Efficacy of Lenalidomide (Revlimid, CC-5013) in Combination With Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma [NCT00306813] | Phase 1/Phase 2 | 53 participants (Anticipated) | Interventional | 2004-09-30 | Completed |
| Evaluation of Lenalidomide (REVLIMID®) in Cutaneous LE: A Prospective, Non Controlled, Open Label Pilot Study to Evaluate the Off-Label Use of the FDA-approved Drug Lenalidomide (REVLIMID®) in Patients With Cutaneous Lupus Erythematosus [NCT00633945] | | 5 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Phase 1 Study of Tasquinimod Alone and in Combination With Standard Therapy for Relapsed or Refractory Myeloma [NCT04405167] | Phase 1 | 34 participants (Anticipated) | Interventional | 2020-07-10 | Recruiting |
| A Phase 1 Dose-Escalation and Exploratory Dose Expansion Study of KRT-232 (AMG 232) in Combination With Carfilzomib, Lenalidomide, and Dexamethasone in Relapsed and/or Refractory Myeloma [NCT03031730] | Phase 1 | 40 participants (Anticipated) | Interventional | 2018-06-14 | Recruiting |
| 2015-12: A Phase II Study Exploring the Use of Early and Late Consolidation/Maintenance With Anti-CD38 (Protein) Monoclonal Antibody to Improve Progression Free Survival in Patients With Newly Diagnosed Multiple Myeloma [NCT03004287] | Phase 2 | 50 participants (Anticipated) | Interventional | 2017-07-01 | Active, not recruiting |
| Randomized Phase III Trial of Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Followed by Limited or Indefinite Duration Lenalidomide Maintenance in Patients With Newly Diagnosed Symptomatic Mult [NCT01863550] | Phase 3 | 1,087 participants (Actual) | Interventional | 2013-12-06 | Active, not recruiting |
| An Open, Single-arm Clinical Study of Lenalidomide Combined With G-CHOP(LO-CHOP) in the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With Follicular Lymphoma (CDLBCL-FL). [NCT06151080] | Phase 2 | 38 participants (Anticipated) | Interventional | 2023-11-22 | Recruiting |
| Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System [NCT05211336] | Phase 1 | 12 participants (Anticipated) | Interventional | 2022-04-19 | Recruiting |
| A Phase II, Multi-center, Open-label, Randomized Study of Vorinostat Plus Lenalidomide and Dexamethasone or Lenalidomide Plus Dexamethasone in Multiple Myeloma Patients Who Experience Biochemical Relapse During Lenalidomide Maintenance Therapy [NCT01501370] | Phase 2 | 0 participants (Actual) | Interventional | 2012-01-31 | Withdrawn |
| Clofarabine Followed by Lenalidomide for Treatment of High Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia [NCT01629082] | Phase 1 | 4 participants (Actual) | Interventional | 2012-06-06 | Completed |
| Phase II Trial With Lenalidomide-Dexamethasone Combination in the Treatment of POEMS Syndrome. [NCT01639898] | Phase 2 | 51 participants (Actual) | Interventional | 2012-07-31 | Completed |
| A Phase I Study of Lenalidomide and Anti-GD2 Mab Ch14.18 +/- Isotretinoin in Patients With Refractory/Recurrent Neuroblastoma [NCT01711554] | Phase 1 | 27 participants (Actual) | Interventional | 2013-02-04 | Active, not recruiting |
| Salvage in Patients With Myelodysplastic Syndrome After Failure of Hypomethylating Agents: Lenalidomide as a Second-line Therapy [NCT01673308] | Phase 2 | 35 participants (Anticipated) | Interventional | 2012-08-31 | Active, not recruiting |
| A Multicenter, Phase I/II Study of Sequential Epigenetic and Immune Targeting in Combination With Nab-Paclitaxel/Gemcitabine in Patients With Advanced Pancreatic Ductal Adenocarcinoma. [NCT04257448] | Phase 1/Phase 2 | 75 participants (Anticipated) | Interventional | 2020-05-25 | Active, not recruiting |
| A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma. [NCT01686386] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2010-02-28 | Recruiting |
| Clinical Study of Azacytidine Combined With Lenalidomide As Maintenance Therapy Based on MRD Monitoring In Elderly or Unfit Patients With Acute Myeloid Leukemia [NCT04490707] | Phase 3 | 60 participants (Anticipated) | Interventional | 2020-09-01 | Recruiting |
| An Open, Multicentric Phase II Trial to Evaluate the Efficacy and Safety of Bendamustine, Lenalidomide (Revlimid®) and Dexamethasone (BRd) as 2nd-line Therapy for Patients With Relapsed or Refractory Multiple Myeloma [NCT01701076] | Phase 2 | 50 participants (Actual) | Interventional | 2012-03-31 | Completed |
| Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-finding Study With Escalating Starting Dose of Lenalidomide and Concomitant Evaluation of Safety and Efficacy [NCT01703364] | Phase 1/Phase 2 | 12 participants (Actual) | Interventional | 2012-06-30 | Completed |
| S1803, Phase III Study of Daratumumab/rHuPH20 (NSC-810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients With Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMAT [NCT04071457] | Phase 3 | 1,100 participants (Anticipated) | Interventional | 2019-08-13 | Recruiting |
| A Pilot Study of DKN-01 and Lenalidomide (Revlimid®)/Dexamethasone Versus Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01711671] | Phase 1 | 8 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Phase 1, Open-Label, Two-Part, Fixed-Sequence Crossover Study to Evaluate the Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Male Subjects [NCT01712828] | Phase 1 | 31 participants (Actual) | Interventional | 2012-10-01 | Completed |
| A Phase 1/2a Dose Escalation Study of PVX-410, a Multi-Peptide Cancer Vaccine, in Patients With Smoldering Multiple Myeloma [NCT01718899] | Phase 1 | 22 participants (Actual) | Interventional | 2012-11-30 | Completed |
| A MULTICENTER, PHASE 1B, OPEN-LABEL STUDY TO DETERMINE THE SAFETY AND ACTIVITY OF CC-292 IN COMBINATION WITH LENALIDOMIDE IN SUBJECTS WITH RELAPSED AND/OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA [NCT01732861] | Phase 1 | 20 participants (Actual) | Interventional | 2012-12-28 | Completed |
| Bendamustine, Lenalidomide and Rituximab (R2-B) Combination as a Second-Line Therapy for First Relapsed-Refractory Mantle Cell Lymphomas: A Phase II Study [NCT01737177] | Phase 2 | 42 participants (Actual) | Interventional | 2012-07-31 | Completed |
| An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study) [NCT01742793] | Phase 1 | 12 participants (Actual) | Interventional | 2012-10-31 | Terminated(stopped due to The study was terminated due to withdrawal of institutional support, Phase II never began.) |
| An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Formulation of IXAZOMIB (MLN9708), Administered Twice-weekly in Combination With Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment [NCT01383928] | Phase 1/Phase 2 | 64 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase II Trial of Mosunetuzumab, Polatuzumab, Tafasitamab, and Lenalidomide in Patients With Relapsed B-cell NHL [NCT05615636] | Phase 2 | 36 participants (Anticipated) | Interventional | 2023-04-28 | Recruiting |
| A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (AS [NCT05257083] | Phase 3 | 750 participants (Anticipated) | Interventional | 2023-10-10 | Recruiting |
| MRD-Guided Sequential Therapy For Deep Response in Newly Diagnosed Multiple Myeloma - MASTER-2 Trial [NCT05231629] | Phase 2 | 300 participants (Anticipated) | Interventional | 2023-12-13 | Recruiting |
| "Phase Ib Trial With Dose Expansion of the Brutons Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab and Lenalidomide in Patients With Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Se [NCT03703167] | Phase 1 | 25 participants (Actual) | Interventional | 2019-01-22 | Active, not recruiting |
| MAGNETISMM-1 A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF ELRANATAMAB (PF-06863135), A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH I [NCT03269136] | Phase 1 | 101 participants (Actual) | Interventional | 2017-11-29 | Active, not recruiting |
| An Expanded Access Program for Elotuzumab in Combination With Lenalidomide Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma in Japan [NCT02856438] | | 0 participants | Expanded Access | | No longer available |
| Phase II Study of the Combination of MLN 9708 With Lenalidomide as Maintenance Therapy Post Autologous Stem Cell Transplant in Patients With Multiple Myeloma [NCT01718743] | Phase 2 | 83 participants (Actual) | Interventional | 2012-12-03 | Completed |
| Phase I Study of Lenalidomide to Augment Anti-Tumor Immunity Following Allogeneic Transplantation [NCT01750762] | Phase 1 | 1 participants (Actual) | Interventional | 2012-12-31 | Terminated |
| A Phase I Trial of Ipilimumab (Anti CTLA- 4 Antibody) in Combination With Lenalidomide (IMiD) in Patients With Advanced Malignancies [NCT01750983] | Phase 1 | 101 participants (Anticipated) | Interventional | 2013-03-31 | Completed |
| HO11415: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) [NCT01754870] | Phase 2 | 0 participants (Actual) | Interventional | 2013-11-30 | Withdrawn(stopped due to slow accrual) |
| A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Tafasitamab Combined With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [NCT05552937] | Phase 2 | 50 participants (Anticipated) | Interventional | 2021-09-06 | Recruiting |
| Lenalidomide in Conjunction With Methotrexate, Leucovorin, Cytarabine and Rituximab for the Treatment of Relapsed or Refractory CD20-positive Aggressive Lymphomas: an Open-label, Multicenter Phase I/II Trial [NCT01788189] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2013-01-31 | Completed |
| An Open-label Phase II Study to Determine the Efficacy and Safety of Lenalidomide Plus Dexamethasone (LDex) in Patients With Newly Diagnosed POEMS Syndrome [NCT01816620] | Phase 2 | 41 participants (Actual) | Interventional | 2014-03-31 | Completed |
| A Pilot Trial of a WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation [NCT01827137] | | 22 participants (Actual) | Interventional | 2013-04-30 | Active, not recruiting |
| Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients on BMT CTN 0702 Protocol (BMT CTN #07LT) [NCT02322320] | Phase 3 | 273 participants (Actual) | Interventional | 2015-03-31 | Completed |
| An Open-Label Study to Determine the Maximum Tolerated Dose and Evaluate the Safety and Efficacy of CEP-18770 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01348919] | Phase 1/Phase 2 | 11 participants (Actual) | Interventional | 2011-08-03 | Completed |
| Impact of First Autologous Transplant on Minimal Residual Disease Markers in Previously Untreated Myeloma Undergoing Initial Treatment With Velcade Based Therapy [NCT01215344] | Phase 2 | 36 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Multi-Center Phase Ib/II Trial of Gemcitabine, Cisplatin, Plus Lenalidomide as First-line Therapy for Patients With Metastatic Urothelial Carcinoma [NCT01342172] | Phase 1/Phase 2 | 9 participants (Actual) | Interventional | 2011-03-31 | Terminated(stopped due to low accrual) |
| Phase II Trial of High Dose Lenalidomide in Patients With Myelodysplastic Syndrome Refractory to Hypomethylating Agents [NCT01246076] | Phase 2 | 24 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Phase 2 Trial of Daily Alternating Thalidomide and Lenalidomide Plus Rituximab (ThRiL) for Patients With Previously Treated Waldenstrom Macroglobulinemia [NCT01779167] | Phase 2 | 4 participants (Actual) | Interventional | 2012-06-30 | Terminated(stopped due to Slow Accrual) |
| Phase I-II Multicenter Study to Assess the Efficacy and Safety of the Chlorambucil + Lenalidomide Combination and Lenalidomide Maintenance Therapy in Untreated Elderly Pts With CLL. EudraCT Number 2009-013415-35 [NCT01403246] | Phase 1/Phase 2 | 9 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to Slow patient enrollment and new molecules for chronic lymphoid leukemia, have importantly reduced the interest of conducting the phase II of this study.) |
| A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Lenalidomide in Patients With Relapsed or Recurrent Adult T-cell Leukemia-lymphoma [NCT01724177] | Phase 2 | 26 participants (Actual) | Interventional | 2012-11-12 | Completed |
| A Phase 1/2a, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD 38 Antibody MOR03087 as Monotherapy and in Combination With Standard Therapy in Subjects With Relapsed/Refractory Multiple My [NCT01421186] | Phase 1/Phase 2 | 91 participants (Actual) | Interventional | 2011-07-31 | Completed |
| A Phase I Clinical Trial to Evaluate the Maximally Tolerated Dose (MTD), Dose Limiting Toxicities (DLTs) and Safety Profiles of Increasing Doses of Lenalidomide After Allo-HCT in AML and MDS Subjects With Minimal Residual Disease (MRD) Detected by the CD3 [NCT02370888] | Phase 1 | 11 participants (Actual) | Interventional | 2016-05-16 | Terminated(stopped due to Slow accrual) |
| Nelfinavir and Lenalidomide/Dexamethasone in Patients With Progressive Multiple Myeloma That Have Failed Lenalidomide-containing Therapy - A Single Arm Phase I/II Trial [NCT01555281] | Phase 1/Phase 2 | 33 participants (Actual) | Interventional | 2012-02-23 | Terminated(stopped due to In connection with the restructuring of SAKK, older ongoing studies were analyzed to determine whether a continuation of the trial would still add value to the data analysis, or whether they do not and could therefore be prematurely terminated.) |
| A Study of Immune-adjuvant Effect of Lenalidomide in Patients With Chronic Lymphocytic Leukemia and Hypogammaglobulinemia and Impaired Response to Vaccinations - RV-CL-CLL-PI-002544 [NCT01924169] | Phase 2 | 3 participants (Actual) | Interventional | 2014-11-24 | Terminated(stopped due to Slow Accrual) |
| A Phase II Randomized Study of Three Subcutaneous Bortezomib-based Consolidation Treatments for Patients Completing Induction Therapy and Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma [NCT01706666] | Phase 2 | 3 participants (Actual) | Interventional | 2012-12-07 | Completed |
| Efficacy and Safety Study of BiRD (Biaxin [Clarithromycin]/Revlimid [Lenalidomide]/Dexamethasone) Combination Therapy in Relapsed/Refractory Myeloma [NCT02986451] | Phase 2 | 0 participants (Actual) | Interventional | 2016-12-31 | Withdrawn |
| Investigation of the Enhancement of the Response to Hepatitis B Vaccine by Lenalidomide (RevlimidTM, CC-5013) in Plasma Cell Dyscrasias [NCT02041325] | Phase 2 | 38 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Short Course Daratumumab in Minimal Residual Disease (MRD) Positive Myeloma Patients After Induction Therapy With/Without Consolidative High Dose Chemotherapy/Autologous Stem Cell Support [NCT03490344] | Phase 2 | 10 participants (Actual) | Interventional | 2018-05-03 | Completed |
| MAGNETISMM-6: AN OPEN-LABEL, 2-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) + DARATUMUMAB + LENALIDOMIDE VERSUS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT-INELIGIBLE PARTICIPANTS [NCT05623020] | Phase 3 | 966 participants (Anticipated) | Interventional | 2022-11-10 | Recruiting |
| A Phase I/IB Pilot Study of CC-486 Combined With Lenalidomide and Obinutuzumab for Relapsed/Refractory Indolent B-Cell Lymphoma [NCT04578600] | Phase 1 | 8 participants (Actual) | Interventional | 2020-10-23 | Active, not recruiting |
| Phase II Study of Lenalidomide in Combination With Rituximab (R) for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL). [NCT01830478] | Phase 2 | 44 participants (Anticipated) | Interventional | 2009-04-30 | Active, not recruiting |
| A Pilot Study of Thalidomide to Overcome Lenalidomide Resistance in Patients Suffering Biochemical Progression on Maintenance Therapy After Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma [NCT01927718] | | 10 participants (Actual) | Interventional | 2014-01-31 | Terminated(stopped due to Poor Response Rate) |
| A Double-blind Placebo Controlled Immunogenicity Study of Vacc-4x + Lenalidomide Versus Vacc-4x With an Initial Open-label Dose Escalation Assessment of Lenalidomide in HIV-1-infected Subjects on Antiretroviral Therapy (ART). [NCT01704781] | Phase 1/Phase 2 | 36 participants (Actual) | Interventional | 2012-09-30 | Completed |
| Multi-center Randomized Study to Compare Efficacy and Safety of Lenalidomide Plus CHOP (L-CHOP) Versus CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma [NCT04922567] | Phase 2 | 289 participants (Anticipated) | Interventional | 2021-04-01 | Recruiting |
| Phase I/Ib Trial of the Efficacy and Safety of Combination Therapy of Lenalidomide/Bortezomib/Dexamethasone and Panobinostat in Transplant Eligible Patients With Newly Diagnosed Multiple Myeloma (MM) [NCT01440582] | Phase 1 | 77 participants (Actual) | Interventional | 2013-02-18 | Completed |
| Exploratory Study of Ixazomib in Combination With Reduced Dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma [NCT05722405] | Phase 4 | 100 participants (Anticipated) | Interventional | 2022-07-01 | Recruiting |
| A Phase I/II Study of Carfilzomib, Lenalidomide, Dexamethasone and the Anti-B-Cell Maturation Antigen (BCMA) Antibody Drug Conjugate Belantamab Mafodotin in Multiple Myeloma [NCT04822337] | Phase 1/Phase 2 | 70 participants (Anticipated) | Interventional | 2021-05-19 | Recruiting |
| Continuing Treatment for Subjects Who Have Participated in a Prior Protocol Investigating Elotuzumab [NCT02719613] | Phase 2 | 67 participants (Actual) | Interventional | 2016-07-15 | Active, not recruiting |
| Phase 2, Randomized, Open-Label Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma Eligible for High-Dose Chemotherapy [NCT02874742] | Phase 2 | 224 participants (Actual) | Interventional | 2016-08-29 | Completed |
| Phase II Study of Lenalidomide and Eltrombopag in Patients With Symptomatic Anemia in Low or Intermediate I Myelodysplastic Syndrome (MDS) [NCT01772420] | Phase 2 | 52 participants (Actual) | Interventional | 2012-10-31 | Completed |
| European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients [NCT01460420] | Phase 1/Phase 2 | 49 participants (Actual) | Interventional | 2011-11-30 | Completed |
| A Phase 2 Clinical Trial To Evaluate Lenalidomide And Obinutuzumab For The Treatment Of Patients With Not Previously Treated Chronic Lymphocytic Leukemia [NCT02371590] | Phase 2 | 0 participants (Actual) | Interventional | 2018-02-28 | Withdrawn(stopped due to Study Not Activated Due to Contract Issues) |
| A Phase II Pilot Study to Determine Efficacy and Safety of Lenalidomide (Revlimid) for Treatment of Autistic Spectrum Disorders(ASD) With Regression and Markers of Cerebrospinal Fluid Cytokine Elevation and Elevated TNF-alpha Levels [NCT00996931] | Phase 2 | 6 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Phase II Study of Lenalidomide and Darbepoetin Alfa in Myelodysplastic Syndrome (Low to Intermediate-1 Risk Category Excluding 5q Deletion) [NCT01222195] | Phase 2 | 1 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to Low accrual.) |
| A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With CHOP in Patients With Untreated PTCL [NCT04423926] | Phase 1/Phase 2 | 91 participants (Anticipated) | Interventional | 2020-06-10 | Recruiting |
| Phase II Study of Revlimid (Lenalidomide), Melphalan, and Dexamethasone (ReMeDex) for Newly Diagnosed Multiple Myeloma Patients Not Undergoing Autologous Transplantation [NCT00843310] | Phase 2 | 8 participants (Actual) | Interventional | 2008-11-30 | Terminated(stopped due to Due to slow accrual) |
| Impact of Short Term Lenalidomide on Immune Response to Prevnar 13® in Individuals With Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Leukemia (SLL), and Monoclonal B Cell Lymphocytosis (MBL) [NCT02309515] | Phase 2 | 12 participants (Actual) | Interventional | 2015-06-11 | Terminated(stopped due to Slow Accrual) |
| A Post-authorization, Non-interventional, Safety Study Study of Patients With Myelodysplastic Syndromes (MDS) Treated With Lenalidomide. [NCT02279654] | | 389 participants (Actual) | Observational [Patient Registry] | 2014-12-17 | Completed |
| A Randomized Phase 2 Trial of Lenalidomide/ Dexamethasone/ Elotuzumab +/- Cyclophosphamide Followed by Lenalidomide/ Dexamethasone/Elotuzumab Maintenance as Second-Line Therapy for Patients With Relapsed AL Amyloidosis [NCT03252600] | Phase 2 | 53 participants (Anticipated) | Interventional | 2017-08-25 | Active, not recruiting |
| Combination of Lenalidomide and Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) [NCT01002755] | Phase 2 | 36 participants (Actual) | Interventional | 2010-01-19 | Completed |
| A Phase I/II Clinical Trial of Lenalidomide in Combination With AT-101 for the Treatment of Relapsed B-Cell Chronic Lymphocytic Leukemia (B-CLL) [NCT01003769] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2015-07-09 | Terminated(stopped due to Lack of funding) |
| A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma [NCT01049945] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2010-02-28 | Completed |
| A Multi-center Phase III Randomized Study Comparing Continuous Versus Fixed Duration Therapy With Daratumumab, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma [NCT03836014] | Phase 3 | 436 participants (Actual) | Interventional | 2019-07-25 | Active, not recruiting |
| Chidamide Combination With Lenalidomide in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma: an Open Label, Single Arm, Phase II Study [NCT04329130] | Phase 2 | 44 participants (Anticipated) | Interventional | 2020-03-27 | Recruiting |
| A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL) [NCT02568553] | Phase 1 | 44 participants (Anticipated) | Interventional | 2016-11-15 | Active, not recruiting |
| Induction Therapy With Bortezomib-melphalan and Prednisone (VMP) Followed by Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab, 18 Cycles, Followed by Consolidation and Maintenance Therapy [NCT03742297] | Phase 3 | 462 participants (Actual) | Interventional | 2018-10-22 | Active, not recruiting |
| A Study of Lenalidomide in Patients With Chronic Lymphocytic Leukemia and Residual Disease After Chemotherapy - RV-CLL-PI-0270 [NCT00632359] | Phase 2 | 33 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A Phase I/II Study of Lenalidomide Maintenance After Autologous Stem Cell Transplant for Elderly Patients With Acute Myeloid Leukemia (AML) [NCT02038153] | Phase 1/Phase 2 | 3 participants (Actual) | Interventional | 2013-12-31 | Terminated(stopped due to Low accrual) |
| Multicenter, Randomized, Double-blind, Phase III Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 IPSS) With Alteration in 5q- and Anemia Without the Need of Transfusion. [NCT01243476] | Phase 3 | 61 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Phase I/II Open Label, Single Center, Study of the Combination of ALX148, Rituximab and Lenalidomide in Patients With Indolent and Aggressive B-Cell Non-Hodgkin Lymphoma [NCT05025800] | Phase 1/Phase 2 | 47 participants (Anticipated) | Interventional | 2021-10-13 | Recruiting |
| A Phase 3, Randomized, Open-label, Parallel-controlled, Multi-center Study Comparing TJ202, Lenalidomide and Dexamethasone vs. Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma Who Received at Least 1 Prior Line of Tr [NCT03952091] | Phase 3 | 291 participants (Actual) | Interventional | 2019-03-27 | Active, not recruiting |
| Rituximab Plus Lenalidomide or Rituximab Monotherapy for Untreated Patients With Follicular Lymphoma in Need of Therapy. A Randomized, Open-Label, Multicenter Phase II Trial. [NCT01307605] | Phase 2 | 154 participants (Actual) | Interventional | 2011-02-09 | Terminated(stopped due to It was decided by the trial team to stop the collection of follow up data in trial SAKK 35/10.) |
| A Phase II Study of Busulfan & Melphalan as Conditioning Regimen for ASCT in Patients Who Received Bortezomib Based Induction for Newly Diagnosed Multiple Myeloma Followed by Lenalidomide Maintenance Until Progression. [NCT01702831] | Phase 2 | 78 participants (Actual) | Interventional | 2013-10-01 | Completed |
| A Pilot Study to Establish the Safety & Efficacy of a Combination of Dexamethasone & Lenalidomide in Patients With Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL) [NCT01459211] | Phase 2 | 12 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A Phase II Study Investigating Treatment of Post-Allogeneic Transplant Progression or Relapse of CLL/SLL/PLL or NHL With Lenalidomide Alone or With Rituximab [NCT01419795] | Phase 2 | 3 participants (Actual) | Interventional | 2012-05-31 | Terminated(stopped due to Low accrual) |
| Phase I Multi-site Study Evaluating the MTD, Safety and Efficacy of the Combination Venetoclax, Lenalidomide and Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma [NCT03523975] | Phase 1 | 30 participants (Actual) | Interventional | 2018-12-24 | Active, not recruiting |
| Open-label, Multicenter Phase I/II Study: Salvage Therapy of Progressive and Relapsed Aggressive Non-Hodgkin-Lymphoma by Combination of Lenalidomide (Revlimid®) With Rituximab, Dexamethason, High-dose ARA-C and Cisplatinum (R²-DHAP) [NCT02983097] | Phase 1/Phase 2 | 34 participants (Actual) | Interventional | 2010-11-30 | Terminated(stopped due to Phase II: no scientific interests are given anymore) |
| Lenalidomide (Revlimid) in Patients With Previously Treated Chronic Lymphocytic Leukemia [NCT00267059] | Phase 2 | 45 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Azacitidine Plus Lenalidomide Combination in Elderly Patients With Previously Treated Acute Myeloid Leukemia (AML) & High-Risk Myelodysplastic Syndromes (MDS) (VIREL2 Trial) [NCT01442714] | Phase 2 | 33 participants (Actual) | Interventional | 2011-08-31 | Terminated(stopped due to Lack of efficacy - Inability to meet the primary response endpoint) |
| [NCT02406144] | Phase 3 | 316 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Phase II Study of Modified Lenalidomide, Bortezomib and Dexamethasone for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma [NCT01782963] | Phase 2 | 50 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Front-line Therapy With Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Induction Followed by Autologous Stem Cell Transplantation, CRd Consolidation and Lenalidomide Maintenance in Newly Diagnosed Multiple Myeloma Patients ≤65 Years Old [NCT02405364] | Phase 2 | 46 participants (Actual) | Interventional | 2014-02-28 | Active, not recruiting |
| Randomized Phase 2 Trial of Retreatment With Pomalidomide or Lenalidomide With Dexamethasone for Patients With Relapsed Myeloma [NCT01794039] | Phase 2 | 9 participants (Actual) | Interventional | 2014-03-31 | Completed |
| ARIA: A Phase 1b/2, Open-label, Multi Cohort Trial of Tazemetostat in Combination With Various Treatments in Subjects With Relapsed or Refractory Hematologic Malignancies [NCT05205252] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2021-12-22 | Withdrawn(stopped due to Epizyme Inc. has revised the Tazemetostat development strategy and made the decision to terminate the hematological malignancies basket trial.) |
| Lenalidomide Combined With Anti-CD20 Monoclonal Antibodies-CHOP in Untreated Diffuse Large B-Cell Lymphoma Patients With MYC and BCL2 Co-expression : An Open-lable，Multicenter，Phase II Study [NCT04842487] | Phase 2 | 80 participants (Anticipated) | Interventional | 2021-04-10 | Not yet recruiting |
| Tislelizumab in Combination With Lenalidomide in in Patients With Relapsed or Refractory Elderly Patients With Non-GCB Diffuse Large B Cell Lymphoma: a Prospective Phase Ib/II, Multicentre, Open-label, Single-arm Trial [NCT04796857] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2021-03-31 | Recruiting |
| A Phase III Study of Lenalidomide and Low-Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Newly Diagnosed and Treatment Naïve Multiple Myeloma (KEYNOTE 185). [NCT02579863] | Phase 3 | 310 participants (Actual) | Interventional | 2015-10-19 | Terminated(stopped due to The study was terminated early due to business reasons) |
| A Phase I/II Study of Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma [NCT05351593] | Phase 1/Phase 2 | 35 participants (Anticipated) | Interventional | 2022-06-08 | Recruiting |
| Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma [NCT02335983] | Phase 1 | 107 participants (Actual) | Interventional | 2015-04-30 | Completed |
| Randomized Phase II Study of Bortezomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Elderly Patients With Newly Diagnosed Multiple Myeloma [NCT04277845] | Phase 2 | 49 participants (Actual) | Interventional | 2020-08-06 | Active, not recruiting |
| Safety and Efficacy of Lenalidomide in the Treatment of Refractory Cutaneous Dermatomyositis [NCT05488327] | | 10 participants (Anticipated) | Interventional | 2022-08-01 | Not yet recruiting |
| Id and Rd Maintenance Regimens After Induction of Remission in Multiple Myeloma: a Prospective, Randomized, Controlled, Multicenter Clinical Study [NCT05477797] | | 420 participants (Anticipated) | Interventional | 2023-02-15 | Not yet recruiting |
| LOC-R01: Randomized Phase IB/II Study of Escalating Doses of Lenalidomide and Ibrutinib in Association With R-MPV as a Targeted Induction Treatment for Patients Aged 18 to 60 (up to 65 for Phase II) With a Newly Diagnosed Primary Central Nervous System Ly [NCT04446962] | Phase 1/Phase 2 | 118 participants (Anticipated) | Interventional | 2020-10-30 | Recruiting |
| Phase II Study Of Durvalumab In Combination With Lenalidomide In Relapsed/Refractory EBV Associated Subtypes Of DLBCL, Primary CNS Lymphoma And Primary Testicular DLBCL - DuRIANS (Durvalumab Revlimid In Aggressive NHL Subtypes) [NCT03212807] | Phase 2 | 0 participants (Actual) | Interventional | 2017-08-31 | Withdrawn(stopped due to FDA Hold for Combination Studies using Imids and PD1/PDL1 Compounds) |
| A Phase II Study of Lenalidomide, Ixazomib, Dexamethasone, and Daratumumab in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma [NCT04009109] | Phase 2 | 188 participants (Anticipated) | Interventional | 2020-10-21 | Recruiting |
| A phaseI/II Safety and Efficacy Trial of a Combination of Bendamustine, Rituximab and Lenalidomide (BRL) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia [NCT01558167] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Multi-center, Open-Label Phase II Study to Determine the Efficacy and Safety of Lenalidomide Plus Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma [NCT01593410] | Phase 2 | 194 participants (Actual) | Interventional | 2010-08-01 | Completed |
| MUK Nine b: OPTIMUM. A Phase II Study Evaluating Optimised Combination of Biological Therapy in Newly Diagnosed High Risk Multiple Myeloma and Plasma Cell Leukaemia. [NCT03188172] | Phase 2 | 95 participants (Anticipated) | Interventional | 2017-09-28 | Active, not recruiting |
| A Multicenter, Prospective, Observational Clinical Protocol for Chidamide in Combination With Rituximab and Lenalidomide (cR2) in Real-world Practice in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma [NCT05690191] | | 169 participants (Anticipated) | Observational | 2021-06-01 | Enrolling by invitation |
| Phase I Trial of High Dose Lenalidomide in Patients With Refractory/Relapsed Acute Leukemia as a Bridge to Bone Marrow Transplant [NCT01615042] | Phase 1 | 6 participants (Actual) | Interventional | 2012-08-31 | Terminated(stopped due to Lack of enrollment) |
| Autologous Peripheral Blood Stem Cell Transplantation and Maintenance Lenalidomide After High-dose Melphalan for Multiple Myeloma [NCT01617213] | Phase 2 | 1 participants (Actual) | Interventional | 2012-04-30 | Terminated(stopped due to Study is no longer needed as recent data have answered the primary hypotheses for this study.) |
| An Open-label, Multicenter,Randomized Phase 2 Trial to Compare the Efficacy and Safety of Ibrutinib Versus Lenalidomide in Combination With MRE(Methotrexate,Rituximab,Etoposide)-Chemotherapy for Adult Patients With Recurrent/Refractory Primary Central Ner [NCT04129710] | Phase 2 | 120 participants (Anticipated) | Interventional | 2020-01-01 | Recruiting |
| R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial. [NCT04120350] | Phase 1/Phase 2 | 47 participants (Anticipated) | Interventional | 2019-08-16 | Recruiting |
| A Phase II Trial of Revlimid® (Lenalidomide) and Low Dose Vidaza® (Azacitidine) in Patients With Low - Intermediate-1 Risk Myelodysplastic Syndromes [NCT01379274] | Phase 2 | 2 participants (Actual) | Interventional | 2011-01-31 | Terminated(stopped due to Loss of funding.) |
| Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients With Previously Untreated Multiple Myeloma [NCT00064038] | Phase 3 | 198 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Phase II Study of CC-5013 in Myelofibrosis [NCT00087672] | Phase 2 | 41 participants (Actual) | Interventional | 2004-07-31 | Completed |
| A Phase II Trial of the Immunomodulatory Drug CC-5013 for Patients With AL Amyloidosis [NCT00091260] | Phase 2 | 82 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Evaluation of Lenalidomide (CC-5013) and Prednisone as a Therapy for Patients With Myelofibrosis (MF) [NCT00352794] | Phase 2 | 40 participants (Actual) | Interventional | 2006-07-07 | Completed |
| Phase II Study of Lenalidomide in Patients With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome Associated With Chromosome 5 Abnormalities [NCT00360672] | Phase 2 | 27 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Phase II Clinical Trial of Lenalidomide for T-cell Non-Hodgkin's Lymphoma [NCT00322985] | Phase 2 | 40 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Controlled, Parallel-Group, Randomized, Open-Label Study to Evaluate Two Lenalidomide Dose Regimens When Used in Combination With Low Dose Dexamethasone for the Treatment of Subjects With Relapsed Multiple Myeloma [NCT01380106] | Phase 2 | 33 participants (Actual) | Interventional | 2010-08-31 | Completed |
| Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Relapsed or Refractory CLL/SLL The HiLOG Trial [NCT01497496] | Phase 2 | 29 participants (Actual) | Interventional | 2012-01-26 | Completed |
| A Phase 2, Multicenter, Single-arm, Open-label Study to Evaluate the Activity, Safety and Pharmacokinetics of Lenalidomide (Revlimid®) in Pediatric Subjects From 1 to = 18 Years of Age With Relapsed or Refractory Acute Myeloid Leukemia. [NCT02538965] | Phase 2 | 17 participants (Actual) | Interventional | 2015-11-19 | Completed |
| Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype [NCT02589145] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2016-06-22 | Terminated(stopped due to Closed due to very slow accrual) |
| Isatuximab in Combination With Bortezomib and Lenalidomide With Minimal Dexamethasone in Transplant-ineligible Multiple Myeloma [NCT04939844] | Phase 2 | 51 participants (Actual) | Interventional | 2021-06-29 | Active, not recruiting |
| A Phase II, Single-Center, Open-Label Study Of Oral Panobinostat (LBH589) When Administered In Combination With Lenalidomide And Weekly Dexamethasone In Patients With Multiple Myeloma [NCT01651039] | Phase 2 | 32 participants (Actual) | Interventional | 2012-07-31 | Completed |
| A Phase I/II Study of the PD-1 Antibody Nivolumab in Combination With Lenalidomide in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD) [NCT03015896] | Phase 1/Phase 2 | 36 participants (Actual) | Interventional | 2017-02-14 | Active, not recruiting |
| A Phase 2, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma in Japan [NCT02272803] | Phase 2 | 82 participants (Actual) | Interventional | 2015-02-20 | Completed |
| A Pilot Study of Lenalidomide as a Chemopreventive Agent for Patients With High-Risk, Early Stage B-Chronic Lymphocytic Leukemia (CLL) [NCT01649791] | | 8 participants (Actual) | Interventional | 2010-01-31 | Terminated |
| A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination With Backbone Treatments for Subjects With Multiple Myeloma [NCT02036502] | Phase 1 | 77 participants (Actual) | Interventional | 2014-02-14 | Terminated(stopped due to Business Reasons) |
| Phase 2 Multi-center Study of Anti-Programmed-Death-1 [Anti-PD-1] During Lymphopenic State After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplant [HDT/ASCT] for Multiple Myeloma [NCT02331368] | Phase 2 | 32 participants (Actual) | Interventional | 2015-06-30 | Completed |
| Phase I/II Trial of the Combination of Lenalidomide (Revlimid) and Nab-paclitaxel (Abraxane) in the Treatment of Relapsed/Refractory Multiple Myeloma [NCT02075021] | Phase 1/Phase 2 | 3 participants (Actual) | Interventional | 2014-03-31 | Terminated(stopped due to PI left the institution) |
| A Phase 3, Single-Arm, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of Tafasitamab Plus Lenalidomide in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [NCT05429268] | Phase 3 | 81 participants (Anticipated) | Interventional | 2022-12-23 | Recruiting |
| A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination With Daratumumab, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Transpla [NCT05280275] | Phase 1/Phase 2 | 36 participants (Anticipated) | Interventional | 2022-04-13 | Recruiting |
| Phase 2 Study of Tafasitamab and Lenalidomide in Relapsed or Refractory Mantle Cell Lymphoma [NCT05788289] | Phase 2 | 39 participants (Anticipated) | Interventional | 2023-03-14 | Recruiting |
| Sequential Treatment With Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia [NCT01743859] | Phase 2 | 37 participants (Actual) | Interventional | 2012-12-06 | Completed |
| A Global Multicenter Phase 1/2 Trial of EO2463, a Novel Microbial-Derived Peptide Therapeutic Vaccine, as Monotherapy, and in Combination With Lenalidomide and Rituximab, for Treatment of Patients With Indolent Non-Hodgkin's Lymphoma [NCT04669171] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2021-07-05 | Recruiting |
| A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Placebo in Subjects With Relapsed/Refractory Indolent Lymphoma [NCT01938001] | Phase 3 | 358 participants (Actual) | Interventional | 2013-11-21 | Completed |
| An Open Label, Single Arm, Multi-Center Exploratory Study to Evaluate the Efficacy and Safety of SVRd for the Treatment of Newly Diagnosed Multiple Myeloma Patients Presenting With Extramedullary Disease. [NCT05900882] | Phase 2 | 35 participants (Anticipated) | Interventional | 2022-07-15 | Recruiting |
| Randomized Phase 1 / 2 Trial of Belantamab Mafodotin, Lenalidomide, and Daratumumab in Relapsed or Newly Diagnosed Multiple Myeloma Patients [NCT04892264] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2021-06-03 | Active, not recruiting |
| A Phase 3 Open-Label Randomized Study to Compare the Efficacy and Safety of Rituximab Plus Lenalidomide (CC-5013) Versus Rituximab Plus Chemotherapy in Subjects With Previously Untreated Follicular Lymphoma [NCT01476787] | Phase 3 | 255 participants (Actual) | Interventional | 2011-12-29 | Active, not recruiting |
| A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies [NCT02265510] | Phase 1/Phase 2 | 83 participants (Actual) | Interventional | 2014-09-10 | Terminated |
| Mechanism Investigation of Selinexor Combined With Lenalidomide and Rituximab in the Treatment of Diffuse Large B-cell Lymphoma [NCT05923879] | | 30 participants (Anticipated) | Observational | 2023-06-30 | Not yet recruiting |
| A RANDOMIZED, MULTICENTER, OPEN LABEL STUDY COMPARING TWO STANDARD TREATMENTS, BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) WITH OR WITHOUT DARATUMUMAB (Dara-VMP) VS LENALIDOMIDE-DEXAMETHASONE (Rd) WITH OR WITHOUT DARATUMUMAB (Dara-Rd) IN AUTOLOGOUS STEM CELL TR [NCT03829371] | Phase 4 | 450 participants (Anticipated) | Interventional | 2019-01-03 | Recruiting |
| A Phase I Study of Obinutuzumab, Venetoclax, and Lenalidomide in Relapsed and Refractory B-cell Non-Hodgkin Lymphoma [NCT02992522] | Phase 1 | 22 participants (Actual) | Interventional | 2017-02-21 | Active, not recruiting |
| A PHASE III, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF STANDARD SCHEDULE VERSUS A NEW ALGORITHM OF DOSE REDUCTIONS IN ELDERLY AND UNFIT NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS RECEIVING LENALIDOMIDE PLUS STEROIDS [NCT02215980] | Phase 3 | 210 participants (Actual) | Interventional | 2014-07-31 | Active, not recruiting |
| A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma [NCT01216683] | Phase 2 | 289 participants (Actual) | Interventional | 2011-02-09 | Completed |
| A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL) [NCT01145495] | Phase 2 | 66 participants (Actual) | Interventional | 2010-06-15 | Completed |
| A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE, MELPHALAN AND PREDNISONE (MPR) Versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS [NCT00551928] | Phase 3 | 402 participants (Actual) | Interventional | 2007-06-30 | Active, not recruiting |
| Phase I/II Double Blind Randomized Trial of Lenalidomide/Dexamethasone/Anakinra vs. Lenalidomide/Dexamethasone/Placebo in Patients With Early Stage Multiple Myeloma and High Plasma Cell Growth Rate [NCT02492750] | Phase 1 | 14 participants (Actual) | Interventional | 2016-04-30 | Completed |
| Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived NK Cells Combined With Rituximab High-Dose Chemotherapy and Autologous Stem Cell Transplant for B-Cell Non-Hodgkin's Lymphoma [NCT03019640] | Phase 2 | 22 participants (Actual) | Interventional | 2017-10-10 | Completed |
| Obinutuzumab, High Dose Methylprednisolone (HDMP), and Lenalidomide for the Treatment of Patients With Richter's Syndrome [NCT03113695] | Phase 1 | 4 participants (Actual) | Interventional | 2017-12-20 | Completed |
| VIRel: Viral Immunotherapy in Relapsed/Refractory Multiple Myeloma - A Phase I Study to Assess the Safety and Tolerability of REOLYSIN® (Pelareorep) in Combination With Lenalidomide or Pomalidomide [NCT03015922] | Phase 1 | 4 participants (Actual) | Interventional | 2017-06-05 | Active, not recruiting |
| Allogeneic Stem Cell Transplantation vs. Conventional Therapy as Salvage Therapy for Relapsed / Progressive Patients With Multiple Myeloma After First-line Therapy [NCT05675319] | Phase 3 | 482 participants (Anticipated) | Interventional | 2023-03-03 | Recruiting |
| Evaluating Mechanisms of Immunomodulator Sensitivity and Resistance in Multiple Myeloma [NCT05288062] | Phase 2 | 190 participants (Anticipated) | Interventional | 2022-03-22 | Recruiting |
| Phase 2 Study of Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for the Treatment of Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia [NCT03118466] | Phase 2 | 41 participants (Actual) | Interventional | 2017-09-25 | Active, not recruiting |
| Phase II Study of Lenalidomide in Combination With Nivolumab In Patients With Relapsed/Refractory Multiple Myeloma [NCT03333746] | Phase 2 | 1 participants (Actual) | Interventional | 2018-03-21 | Terminated(stopped due to Study was discontinued due to FDA recommendations of the potential toxicities of the combination of drugs.) |
| A Phase Ib/IIa Clinical Study of IMM0306 fo r Injection in Combination With Lenalidomide for the Treatment of Relapsed/Refractory CD20-Positive B-Cell Non-Hodgkin's Lymphoma Cell Non-Hodgkin's Lymphoma [NCT05771883] | Phase 1/Phase 2 | 102 participants (Anticipated) | Interventional | 2023-05-31 | Not yet recruiting |
| National, Open-label, Multicentre Phase I-II Study of Combination R-ESHAP With Lenalidomide as Salvage Therapy for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma Candidates to Stem-cell Transplantation [NCT02340936] | Phase 1/Phase 2 | 53 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase II Study of Once Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Isatuximab in Newly Diagnosed, Transplant-Eligible Multiple Myeloma [NCT04430894] | Phase 2 | 50 participants (Actual) | Interventional | 2020-07-10 | Active, not recruiting |
| A Phase II Trial of Daratumumab, Lenalidomide and Dexamethasone (DRd) in Combination With Selinexor for Patients With Newly Diagnosed Multiple Myeloma [NCT04782687] | Phase 2 | 100 participants (Anticipated) | Interventional | 2021-09-10 | Recruiting |
| Rituximab,Zanubrutinib in Combination With Lenalidomide, Followed by Zanubrutinib or Lenalidomide Maintenance in Patients With Primary or Secondary CNS Lymphoma [NCT04938297] | Phase 2 | 100 participants (Anticipated) | Interventional | 2021-05-26 | Recruiting |
| Lenalidomide and Dexamethasone for Rosai-Dorfman Disease: A Single Arm, Single Center, Prospective Phase 2 Study [NCT04924647] | Phase 2 | 16 participants (Anticipated) | Interventional | 2021-06-08 | Recruiting |
| A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed MCL [NCT03232307] | Phase 2 | 0 participants (Actual) | Interventional | 2019-07-01 | Withdrawn(stopped due to Sponsor does not wish to proceed) |
| GEM21menos65. A Phase III Trial for NDMM Patients Who Are Candidates for ASCT Comparing Extended VRD Plus Early Rescue Intervention vs Isatuximab-VRD vs Isatuximab-V-Iberdomide-D [NCT05558319] | Phase 3 | 480 participants (Anticipated) | Interventional | 2022-10-31 | Not yet recruiting |
| A Phase 1a/1b Multicenter, Open Label, Dose-Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of CWP232291 Administered Intravenously Either Alone or in Combination With Lenalidomide and Dexamethasone in Subjects With Relapse [NCT02426723] | Phase 1 | 25 participants (Actual) | Interventional | 2015-10-19 | Completed |
| A Phase 2 Clinical Trial To Evaluate The Immune Restoration Potential Of Lenalidomide For Patients With CLL-Associated Immunodeficiency [NCT02371577] | Phase 2 | 0 participants (Actual) | Interventional | 2017-02-01 | Withdrawn(stopped due to withdrawn) |
| Efficacy and Safety Study of Lenalidomide Plus Rituximab and Methotrexate Chemotherapy（R2-MTX） Versus Rituximab and Methotrexate Chemotherapy（R-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma: a Multicenter, Open-Label, Randomised Phase 2 [NCT04481815] | Phase 2 | 240 participants (Anticipated) | Interventional | 2020-10-01 | Recruiting |
| A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome [NCT04623541] | Phase 1/Phase 2 | 184 participants (Anticipated) | Interventional | 2020-11-25 | Recruiting |
| Phase I/II Study of Lenalidomide Combined With Modified DA-EPOCH and Rituximab (EPOCH-R2) in Primary Effusion Lymphoma or KSHV-Associated Large Cell Lymphoma [NCT02911142] | Phase 1/Phase 2 | 12 participants (Actual) | Interventional | 2017-07-03 | Active, not recruiting |
| A Phase I/II Study of Lenalidomide in Patients With AIDS-Associated Kaposi's Sarcoma [NCT01057121] | Phase 1/Phase 2 | 38 participants (Actual) | Interventional | 2010-08-27 | Completed |
| Selinexor(ATG-010) Plus Bortezomib, Lenalidomide and Dexamethasone (XVRd) in High Risk Newly Diagnosed Multiple Myeloma [NCT05422027] | Phase 1/Phase 2 | 42 participants (Anticipated) | Interventional | 2022-07-25 | Recruiting |
| Administration of an Oral PDE5 Inhibitor, Tadalafil in Conjunction With Lenalidomide and Dexamethasone in Patients With Multiple Myeloma [NCT01374217] | Phase 2 | 14 participants (Actual) | Interventional | 2012-04-30 | Terminated(stopped due to early stopping rule) |
| Selinexor in Combination With Immunomodulator to Treat Relapsed/Refractory Multiple Myeloma Patients [NCT04941937] | Phase 2 | 90 participants (Anticipated) | Interventional | 2022-01-27 | Recruiting |
| A Real-world Study of the Efficacy and Safety of Obinutuzumab-based Therapy for Previously Untreated Follicular Lymphoma [NCT05899621] | | 332 participants (Anticipated) | Observational | 2023-06-01 | Recruiting |
| Phase I-II Single Cycle Melphalan/Total Marrow Irradiation (TMI) and Autologous Stem Cell Transplantation (ASCT) Followed by Maintenance in Patients With High-Risk Myeloma and/or Poor Response to Induction Therapy Within 12 Months of Diagnosis [NCT03100877] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2018-01-31 | Withdrawn(stopped due to Feasibility Issues) |
| Efficacy and Safety of Tislelizumab Combined Treatment in Refractory Natural Killer/T-cell Lymphoma [NCT05058755] | | 62 participants (Anticipated) | Interventional | 2021-09-17 | Recruiting |
| A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma [NCT05821088] | Phase 2 | 37 participants (Anticipated) | Interventional | 2023-06-29 | Recruiting |
| Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase 3 Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation [NCT04566328] | Phase 3 | 1,450 participants (Anticipated) | Interventional | 2021-02-24 | Recruiting |
| Daratumumab to Enhance Therapeutic Effectiveness of Revlimid in Smoldering Myeloma (DETER-SMM) [NCT03937635] | Phase 3 | 288 participants (Anticipated) | Interventional | 2019-09-16 | Recruiting |
| Multicenter Phase II Study to Demonstrate Clinical Benefit of Lenalidomide and Dexamethasone in Elderly Unfit Patients With Newly Diagnosed Multiple Myeloma [NCT03809780] | Phase 2 | 70 participants (Actual) | Interventional | 2019-03-11 | Active, not recruiting |
| Phase 2 Trial of Ixazomib, Lenalidomide, Dexamethasone, and Daratumumab in Patients With Newly Diagnosed Multiple Myeloma [NCT03012880] | Phase 2 | 80 participants (Actual) | Interventional | 2017-04-12 | Active, not recruiting |
| Phase I Trial of the Combination of Ibrutinib and Lenalidomide for the Treatment of Patients With MDS Who Have Failed or Refuse Standard Therapy [NCT03359460] | Phase 1 | 4 participants (Actual) | Interventional | 2017-12-01 | Completed |
| A Phase 3, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of Clarithromycin(Biaxin)-Lenalidomide-Low-Dose-Dexamethasone (BiRd) Combined With B-cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-cell Therapy in Pati [NCT04287660] | Phase 3 | 20 participants (Anticipated) | Interventional | 2017-10-19 | Recruiting |
| Lenalidomide for the Treatment of CLL Patients With High-Risk Disease [NCT01271283] | Phase 2 | 0 participants (Actual) | Interventional | 2010-12-31 | Withdrawn |
| Lenalidomide and Rituximab Treatment of Relapsed Mantle Cell Lymphoma and Diffuse Large B-Cell Non-Hodgkin's Lymphoma, Transformed Large Cell Lymphoma, and/or Grade 3 Follicular Lymphoma (Follicular Cleaved Large Cell Lymphoma or Follicular Non-Cleaved La [NCT00294632] | Phase 1/Phase 2 | 54 participants (Actual) | Interventional | 2006-02-28 | Completed |
| A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer [NCT00942578] | Phase 2 | 63 participants (Actual) | Interventional | 2009-07-16 | Completed |
| A Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Lymphodepleting Chemotherapy and Lenalidomide as Immunotherapy in Patients With Hematologic Malignancies [NCT02280525] | Phase 1 | 8 participants (Actual) | Interventional | 2015-03-05 | Completed |
| A Phase 2, Multicenter, Open-label, Single Arm Study of Lenalidomide (CC-5013) in Combination With Low-dose Dexamethasone in Japanese Patients With Previously Untreated Multiple Myeloma [NCT01698801] | Phase 2 | 26 participants (Actual) | Interventional | 2012-10-01 | Completed |
| REsponse Adapted Combination Therapy Approaches for High-Risk Multiple Myeloma (REACH) [NCT05497804] | Phase 2 | 75 participants (Anticipated) | Interventional | 2022-09-22 | Recruiting |
| A Phase 3, Intergroup Multicentre, Randomized, Controlled 3 Arm Parallel Group Study to Determine the Efficacy and Safety of Lenalidomide in Combination With Dexamethasone (RD) Versus Melphalan, Prednisone and Lenalidomide (MPR) Versus Cyclophosphamide, P [NCT01093196] | Phase 3 | 660 participants (Anticipated) | Interventional | 2009-10-31 | Active, not recruiting |
| A Phase 3, Multicentre, Randomized, Controlled Study to Determine the Efficacy and Safety of Cyclophosphamide, Lenalidomide and Dexamethasone (CRD) Versus Melphalan (200 mg/m2) Followed By Stem Cell Transplant In Newly Diagnosed Multiple Myeloma Subjects [NCT01091831] | Phase 3 | 389 participants (Actual) | Interventional | 2009-07-31 | Active, not recruiting |
| Phase I/II Study of Lenalidomide and Gemcitabine as First-line Treatment in Patients With Locally Advanced or Metastatic Pancreatic Cancer [NCT01547260] | Phase 1/Phase 2 | 34 participants (Actual) | Interventional | 2009-10-31 | Completed |
| Phase 2 Study of Isatuximab Plus Lenalidomide and Dexamethasone in Highly Toxicity-vulnerable Subjects With Newly Diagnosed Multiple Myeloma [NCT05145400] | Phase 2 | 50 participants (Anticipated) | Interventional | 2022-02-18 | Recruiting |
| An Open-Label Phase I/II Study of the Safety and Efficacy of Bortezomib, Lenalidomide and Dexamethasone Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma [NCT00378105] | Phase 1/Phase 2 | 68 participants (Actual) | Interventional | 2006-09-30 | Active, not recruiting |
| Phase II Study of CC-5103 and Rituximab in Waldenstrom's Macroglobulinemia [NCT00142168] | Phase 2 | 16 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to Toxicity) |
| Phase III, Multicenter, Open Label, Randomized, Controlled Study Investigating Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma [NCT06006117] | Phase 3 | 260 participants (Anticipated) | Interventional | 2023-09-05 | Recruiting |
| A Phase 1b/2 Study of Tafasitamab, Tafasitamab Plus Lenalidomide, Tafasitamab Plus Parsaclisib, and Tafasitamab Plus Lenalidomide in Combination With R-CHOP in Japanese Participants With Non-Hodgkin Lymphoma [NCT04661007] | Phase 1 | 65 participants (Anticipated) | Interventional | 2020-12-15 | Recruiting |
| Symphony-1: A Phase 1b/3 Double-Blind, Randomized, Active-Controlled, 3-Stage, Biomarker Adaptive Study Of Tazemetostat Or Placebo In Combination With Lenalidomide Plus Rituximab In Subjects With Relapsed/Refractory Follicular Lymphoma [NCT04224493] | Phase 3 | 540 participants (Anticipated) | Interventional | 2019-12-19 | Recruiting |
| A Multiple-center Phase 2 Study of Acalabrutinib-Lenalidomide-Rituximab in Patients With Previous Untreated Mantle Cell Lymphoma [NCT03863184] | Phase 2 | 24 participants (Anticipated) | Interventional | 2019-10-11 | Recruiting |
| Ixazomib, Lenalidomide, and Dexamethasone for Patients With POEMS Syndrome [NCT02921893] | Early Phase 1 | 21 participants (Actual) | Interventional | 2016-10-31 | Active, not recruiting |
| A Phase II Study of Lenalidomide Following Allogeneic Stem Cell Transplant for Multiple Myeloma Patients Who Relapse or Have Disease Progression [NCT00619684] | Phase 2 | 18 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab Followed by Consolidation With Lenalidomide for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) [NCT00602836] | Phase 2 | 45 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase II Trial of Rituximab Plus Lenalidomide in Patients With Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT) Type [NCT01611259] | Phase 2 | 50 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A Phase 1/2 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients With Myelodysplastic Syndrome (RAEB-2) or With Previously Untreated Acute Myeloid Leukemia [NCT00831766] | Phase 1/Phase 2 | 51 participants (Actual) | Interventional | 2009-06-25 | Completed |
| A Phase I/Randomized Phase II Trial of Idelalisib and Lenalidomide in Patients With Relapsed/Refractory Mantle Cell Lymphoma [NCT01838434] | Phase 1 | 106 participants (Actual) | Interventional | 2013-07-31 | Completed |
| Phase I/II Study of Lenalidomide in Combination With Anti-PD-1 Monoclonal Antibody CT-011 in Patients With Relapsed/Refractory Multiple Myeloma [NCT02077959] | Phase 1 | 20 participants (Actual) | Interventional | 2014-03-03 | Terminated(stopped due to Pharmaceutical Companies decision) |
| A Prospective Phase II Clinical Study of Orelabrutinib in Combination With Lenalidomide and Rituximab (OLR) in First-line Treatment of Mantle Cell Lymphoma [NCT05076097] | Phase 2 | 29 participants (Anticipated) | Interventional | 2021-09-30 | Recruiting |
| Lenalidomide Maintenance Therapy in Multiple Myeloma: A Phase II Clinical and Biomarker Study [NCT01675141] | Phase 2 | 11 participants (Actual) | Interventional | 2012-08-20 | Terminated(stopped due to Original investigator left the NIH and the primary outcome was not reached) |
| A Phase 1B/2 Randomized, Multicenter, Open-Label Study Of Iberdomide (CC-220) In Combination With Polatuzumab Vedotin Plus Rituximab Or Tafasitamab Or Rituximab Plus Chemotherapy For Subjects With Relapsed Or Refractory Aggressive B-Cell Lymphoma [NCT04882163] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2021-10-10 | Withdrawn(stopped due to Business objectives have changed) |
| Empliciti® (Elotuzumab) Post-Marketing Surveillance Study for Patients With Multiple Myeloma in Taiwan [NCT06163040] | | 27 participants (Anticipated) | Observational | 2023-11-30 | Not yet recruiting |
| A Phase I/II Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma [NCT01297764] | Phase 1/Phase 2 | 17 participants (Actual) | Interventional | 2011-04-30 | Active, not recruiting |
| A Phase Ib/II Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Obinutuzumab Plus Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma [NCT02631577] | Phase 1/Phase 2 | 38 participants (Actual) | Interventional | 2015-12-31 | Completed |
| Phase II Trial of the PD-1 Antibody Nivolumab in Combination With Lenalidomide and Low Dose Dexamethasone in Patients With High-Risk Smoldering Multiple Myeloma [NCT02903381] | Phase 2 | 8 participants (Actual) | Interventional | 2016-10-20 | Completed |
| Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Clinical and Correlative Phase II Study [NCT01402284] | Phase 2 | 45 participants (Actual) | Interventional | 2011-07-21 | Completed |
| Phase 1 Study of Daratumumab When Given in Combination With Bortezomib, Dexamethasone, Doxil, and Lenalidomide in Patients With Plasma Cell Leukemia [NCT03591744] | Phase 1 | 0 participants (Actual) | Interventional | 2018-10-25 | Withdrawn(stopped due to Budgetary constraints) |
| Revlimid to Augment Efficacy of Prevnar Vaccines in Patients With Relapsed or Refractory Myeloma [NCT00445484] | Phase 2 | 22 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Pilot Clinical Trial of Lenalidomide (Revlimid®) for the Treatment of Refractory Cancer Pain [NCT00684242] | Phase 2 | 4 participants (Actual) | Interventional | 2008-05-31 | Terminated(stopped due to Low accrual.) |
| Phase I/II Study of Sorafenib, Lenalidomide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma [NCT00687674] | Phase 1 | 13 participants (Actual) | Interventional | 2008-08-31 | Terminated(stopped due to Due to study design (and toxicity), this trial closed to accrual prior to opening the phase II portion.) |
| A Multi-Institutional Phase I/II Study of Revlimid® (Lenalidomide), Velcade® (Bortezomib), Dexamethasone, and Doxil®, (RVDD) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma [NCT00724568] | Phase 1/Phase 2 | 74 participants (Actual) | Interventional | 2008-05-31 | Completed |
| A Phase 1 Study of Amrubicin in Combination With Lenalidomide and Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma [NCT01355705] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A Phase Ib Multi-Cohort Trial of MK-3475 (Pembrolizumab) in Subjects With Hematologic Malignancies [NCT01953692] | Phase 1 | 197 participants (Actual) | Interventional | 2013-11-22 | Completed |
| Single Agent Lenalidomide in Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) [NCT01401322] | Phase 2 | 5 participants (Actual) | Interventional | 2011-01-31 | Terminated(stopped due to low accrual) |
| A Phase I Study of Lenalidomide Plus Pembrolizumab in Patients With Relapsed and/or Refractory Solid Tumors With Phase II Expansion in Non-small Cell Lung Cancer [NCT02963610] | Phase 1/Phase 2 | 3 participants (Actual) | Interventional | 2017-03-29 | Terminated(stopped due to Study terminated prematurely due to funding/support being withdrawn by grantor) |
| 2015-09: A Phase II Randomized, Open-label Study of Anti-SLAMF7 mAb During Maintenance Therapy Versus Standard Maintenance Therapy in Gene Expression Profiling (GEP)- Defined Low Risk Multiple Myeloma Patients With High Risk Cytogenetic Abnormalities [NCT03000634] | Phase 2 | 0 participants (Actual) | Interventional | 2017-05-31 | Withdrawn(stopped due to Study was not and will not be initiated due to lack of funding.) |
| Myeloma Cure Project: Prospective, Randomized Trial of Indefinite Revlimid Maintenance Versus Observation for Currently Event-Free Patients With Multiple Myeloma Who Have Completed 3 Years of VTD/TD or VTD or VRD Maintenance on Total Therapy 3 (TT3) Trial [NCT01621672] | Phase 3 | 42 participants (Actual) | Interventional | 2010-04-30 | Completed |
| A Randomized Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma [NCT02495922] | Phase 3 | 564 participants (Actual) | Interventional | 2015-06-30 | Completed |
| Functional Cure Strategy and Clinical Study of AIDS--Study on the Reduction of HIV Viral Reservoir by Immunomodulators (IMs) [NCT05598580] | Phase 4 | 48 participants (Anticipated) | Interventional | 2022-11-20 | Recruiting |
| Phase I/II Study of Lenalidomide in Combination With Rituximab, Ifosfamide, Etoposide, and Carboplatin (RICER) [NCT01241734] | Phase 1/Phase 2 | 18 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Phase II Open Label Study for the Assessment of the Efficacy and Safety of Lenalidomide & Adriamycin & Low Dose Dexamethasone (RAD) in Newly Diagnosed, Symptomatic Multiple Myeloma Patients [NCT02471820] | Phase 2 | 45 participants (Actual) | Interventional | 2014-11-30 | Completed |
| [NCT01450215] | Phase 2 | 62 participants (Actual) | Interventional | 2011-03-31 | Completed |
| A Dose Escalation Study of Ibrutinib With Lenalidomide for Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma [NCT01886859] | Phase 1 | 27 participants (Actual) | Interventional | 2013-04-26 | Completed |
| Phase 1/2 Study of the Combination of Glofitamab, Venetoclax and Lenalidomide in Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma [NCT05861050] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2023-08-10 | Recruiting |
| Carfilzomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma: A Randomized Phase II Study. [NCT03673826] | Phase 2 | 58 participants (Actual) | Interventional | 2018-11-19 | Active, not recruiting |
| A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed/Refractory Multiple Myeloma (RRMM) Patients [NCT03110822] | Phase 1 | 134 participants (Anticipated) | Interventional | 2017-02-01 | Recruiting |
| A Phase 2 Study of Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib [NCT02294357] | Phase 2 | 45 participants (Anticipated) | Interventional | 2014-12-31 | Terminated(stopped due to Early termination due to the difficulties to enroll subjects.) |
| An Open Label, Single-Arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Lenalidomide, Bortezomib, Dexamethasone and Siltuximab (CNTO 328) in Subjects With Newly Diagnosed, Previously Untreated Multiple Myeloma Requiring System [NCT01531998] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A PHASE 1b/2 STUDY OF PF-07901801, A CD47 BLOCKING AGENT, WITH TAFASITAMAB AND LENALIDOMIDE FOR PARTICIPANTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA NOT ELIGIBLE FOR STEM CELL TRANSPLANTATION [NCT05626322] | Phase 2 | 70 participants (Anticipated) | Interventional | 2023-08-04 | Recruiting |
| Phase I/II, Open-Label Study of R-ICE (Rituximab-Ifosfamide-Carboplatin-Etoposide) With Lenalidomide (R2-ICE) in Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT02628405] | Phase 1/Phase 2 | 63 participants (Actual) | Interventional | 2016-05-20 | Active, not recruiting |
| A Randomized, Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib, and Dexamethasone (RVD) to High-Dose Treatment With Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients Up to [NCT01208662] | Phase 3 | 729 participants (Actual) | Interventional | 2010-10-31 | Active, not recruiting |
| Maintenance Therapy With Lenalidomide Following Bendamustine and Rituximab Induction Therapy for Chronic Lymphocytic Leukemia [NCT01465230] | Phase 2 | 2 participants (Actual) | Interventional | 2012-03-31 | Terminated(stopped due to This study was unsuccessful in enrolling the target number of subjects during the funding period.) |
| A Phase III Multicenter, Randomized Study With Lenalidomide Maintenance vs Observation After Induction Regimen Containing Rituximab Followed by High Dose Chemotherapy and ASCT as First Line Treatment in Adult Patients With Advanced Mantle Cell Lymphoma [NCT02354313] | Phase 3 | 300 participants (Anticipated) | Interventional | 2010-05-31 | Active, not recruiting |
| Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study [NCT01054196] | Phase 1/Phase 2 | 52 participants (Actual) | Interventional | 2010-08-31 | Active, not recruiting |
| Phase 3 Randomized, Double-Blind, Placebo Controlled, Multicenter Study to Compare the Efficacy and Safety of Lenalidomide (CC-5013) Plus R-CHOP Chemotherapy (R2-CHOP) Versus Placebo Plus R-CHOP Chemotherapy in Subjects With Previously Untreated Activated [NCT02285062] | Phase 3 | 570 participants (Actual) | Interventional | 2015-02-17 | Completed |
| Phase II Study: Therapy With Bortezomib + Lenalidomide + Dexamethasone With Lenalidomide + Dexamethasone as Post Transplant Consolidation and Maintenance for Patients With Symptomatic Multiple Myeloma Following Autologous Transplantation [NCT02353468] | Phase 2 | 3 participants (Actual) | Interventional | 2009-12-31 | Terminated(stopped due to Principle investigator left the institution) |
| A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma [NCT01749969] | Phase 1 | 57 participants (Actual) | Interventional | 2013-02-06 | Completed |
| Phase II Study of CC-5013 in Patients With Advanced Renal Cell Carcinoma (RCC) [NCT00403169] | Phase 2 | 26 participants (Anticipated) | Interventional | 2004-08-31 | Completed |
| Efficacy and Safety of Rituximab Plus Zanubrutinib and Lenalidomide for Relapsed and Refractory Diffuse Large B Cell Lymphoma, a Multicenter, Open and Prospective Clinical Trial [NCT05392257] | Phase 2 | 20 participants (Anticipated) | Interventional | 2022-05-01 | Recruiting |
| A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Relapse/Refractory Waldenstrom Macroglobulinemia [NCT02302469] | Phase 1/Phase 2 | 17 participants (Actual) | Interventional | 2009-03-31 | Completed |
| Prospective Observational Study Evaluating the Safety of Lenalidomide/Dexamethasone Treatment in Patients With Relapsed or Refractory Multiple Myeloma [NCT02692339] | | 22 participants (Actual) | Observational [Patient Registry] | 2016-02-25 | Completed |
| Phase 3, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Relapsed or Refractory Multiple Myeloma (MM) [NCT01239797] | Phase 3 | 646 participants (Actual) | Interventional | 2011-06-20 | Completed |
| The Efficacy and Safety of Lenalidomide With or Without Rituximab and Other Drugs in B-cell Non-Hodgkin Lymphomas: a Real-world Study. [NCT04435743] | | 1,000 participants (Anticipated) | Observational | 2019-11-01 | Recruiting |
| A Randomized Phase III Non-inferiority Trial Assessing Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Transplant-eligible Patients With Newly Diagnosed Multiple Myeloma. [NCT05804032] | Phase 3 | 514 participants (Anticipated) | Interventional | 2023-04-14 | Recruiting |
| A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) - DRE [NCT04126200] | Phase 1/Phase 2 | 464 participants (Anticipated) | Interventional | 2019-10-07 | Recruiting |
| Sequential Chemotherapy and Lenalidomide Followed by Rituximab and Lenalidomide Maintenance for Untreated Mantle Cell Lymphoma: A Phase II Study [NCT02633137] | Phase 2 | 49 participants (Actual) | Interventional | 2015-12-14 | Completed |
| A Phase I Study of Ibrutinib (PCI-32765) in Combination With Lenalidomide in Relapsed and Refractory B-Cell Non-Hodgkin's Lymphoma [NCT01955499] | Phase 1 | 34 participants (Anticipated) | Interventional | 2013-09-13 | Active, not recruiting |
| A Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma [NCT01829568] | Phase 1 | 33 participants (Actual) | Interventional | 2013-06-21 | Active, not recruiting |
| Phase II Study of Lenalidomide to Repair Immune Synapse Response and Humoral Immunity in Early-Stage, Asymptomatic Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) With High-Risk Genomic Features [NCT01351896] | Phase 2 | 48 participants (Anticipated) | Interventional | 2011-09-08 | Active, not recruiting |
| A Randomized, Phase 2 Study of Biomarker Guided Treatment in DLBCL [NCT04025593] | Phase 2 | 128 participants (Anticipated) | Interventional | 2019-07-17 | Recruiting |
| A Single Arm，Phase Ib/II Study of the Combination of Lenalidomide and Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphomas (PTCL) [NCT05105412] | Phase 1/Phase 2 | 33 participants (Anticipated) | Interventional | 2021-10-31 | Not yet recruiting |
| Carfilzomib (K) Plus Lenalidomide (R) and Dexamethasone (D) for BTK Inhibitors Relapsed-refractory or Intolerant Mantle Cell Lymphomas: a Phase II Study [NCT03891355] | Phase 2 | 16 participants (Actual) | Interventional | 2019-09-30 | Active, not recruiting |
| A Phase I, Multiple Center, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CM313 in Subjects With Relapsed or Refractory Multiple Myeloma and Lymphoma [NCT04818372] | Phase 1 | 87 participants (Anticipated) | Interventional | 2021-04-26 | Recruiting |
| Lenalidomide in Combination With Rituximab as Treatment for Patients With Relapsed Chronic Lymphocytic Leukemia - RV-CLL-PI-0292 [NCT00759603] | Phase 2 | 60 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma [NCT01881789] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2013-10-28 | Terminated(stopped due to A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ003 was halted during dose-escalation.) |
| First-in-Human Study of the BCL-2 Inhibitor ABBV-453 in Biomarker-Selected Subjects With Relapsed or Refractory Multiple Myeloma [NCT05308654] | Phase 1 | 360 participants (Anticipated) | Interventional | 2022-05-17 | Recruiting |
| Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia - MILESTONE Trial [NCT04991103] | Phase 2 | 20 participants (Anticipated) | Interventional | 2021-09-22 | Recruiting |
| A Phase I Study of Ibrutinib (PCI-32765) in Combination With Revlimid/Dexamethasone (Rd) in Relapsed/Refractory Multiple Myeloma [NCT03702725] | Phase 1 | 14 participants (Actual) | Interventional | 2019-08-29 | Active, not recruiting |
| A MULTICENTER, RANDOMIZED, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (CCyd) as Pre Transplant INDUCTION and Post Transplant Consolidation or CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (CRd) as Pre Transplant INDUCTION a [NCT02203643] | Phase 2 | 477 participants (Actual) | Interventional | 2015-02-28 | Active, not recruiting |
| Phase-II Trial to Assess the Efficacy and Safety of Lenalidomide in Addition to 5-Azacitidine and Donor Lymphocyte Infusions (DLI) for the Treatment of Patients With MDS, CMML or AML Who Relapse After Allogeneic Stem Cell Transplantation [NCT02472691] | Phase 2 | 50 participants (Actual) | Interventional | 2015-05-31 | Completed |
| Solitary Plasmacytoma of Bone: Randomized Phase III Trial to Evaluate Treatment With Adjuvant Systemic Treatment and Zoledronic Acid Versus Zoledronic Acid After Definite Radiation Therapy [NCT02516423] | Phase 3 | 11 participants (Actual) | Interventional | 2015-12-31 | Active, not recruiting |
| A Randomized Clinical Trial of Lenalidomide (CC-5013) and Dexamethasone With and Without Autologous Peripheral Blood Stem Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma [NCT01731886] | Phase 4 | 60 participants (Actual) | Interventional | 2012-09-30 | Completed |
| Phase I/II Study of Lenalidomide and Ofatumumab for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma [NCT01060384] | Phase 1/Phase 2 | 46 participants (Actual) | Interventional | 2010-03-29 | Completed |
| An Open-label, Randomized, Single Dose, Crossover Bioequivalent Study to Compare Pharmacokinetic Property of SYP-1512 Tab and Revlimid Cap, 25mg in Healthy Male Volunteers [NCT03208218] | Phase 1 | 42 participants (Actual) | Interventional | 2016-08-17 | Completed |
| Assessment of Survival and Autonomy With Rituximab Plus Chemotherapy or Rituximab Plus Lenalidomide for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma [NCT04113226] | Phase 2 | 114 participants (Anticipated) | Interventional | 2021-07-26 | Recruiting |
| A Randomized Phase II Study of Oral Lenalidomide (Revlimid [TM]), an Antiangiogenic and Immunomodulatory Agent, in Subjects With Stage IV Ocular Melanoma [NCT00109005] | Phase 2 | 17 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial [NCT00112827] | Phase 1/Phase 2 | 54 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Phase II Study of Lenalidomide Maintenance in Patients With High Risk AML in Remission [NCT02126553] | Phase 2 | 29 participants (Actual) | Interventional | 2014-11-13 | Completed |
| A Multi-Center, Phase 1/2, Open-Label Study of Selinexor (KPT- 330), Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma [NCT02389543] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2015-07-31 | Withdrawn(stopped due to Terminated this trial and added a Lenalidomide arm to KCP-330-017) |
| A Phase II Trial of Revlimid® as Consolidation Treatment of Residual Disease in Patients With Chronic Lymphocytic Leukemia (CLL) [NCT01600053] | Phase 2 | 11 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to interim analysis showed that the trial will not meet the interim endpoint.) |
| Multicenter Open Label Phase 3 Study of Isatuximab Plus Lenalidomide and Dexamethasone With/Without Bortezomib in the Treatment of Newly Diagnosed Non Frail Transplant Ineligible Multiple Myeloma Elderly Patients (≥ 65; < 80 Years). [NCT04751877] | Phase 3 | 270 participants (Actual) | Interventional | 2021-07-17 | Active, not recruiting |
| A Phase II Study of Sequential Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Newly Diagnosed Multiple Myeloma [NCT01559935] | Phase 2 | 74 participants (Actual) | Interventional | 2012-03-31 | Active, not recruiting |
| A Phase 2 Single Arm Study of Safety of Elotuzumab Administered Over Approximately 60 Minutes in Combination With Lenalidomide and Dexamethasone for Newly Diagnosed or Relapsed/Refractory Multiple Myeloma Patients [NCT02159365] | Phase 2 | 84 participants (Actual) | Interventional | 2014-03-08 | Completed |
| A Phase 3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3) [NCT03651128] | Phase 3 | 381 participants (Actual) | Interventional | 2019-04-16 | Active, not recruiting |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00056160 (4) [back to overview] | Time to First Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (Best Score=0, Fully Active, Able to Carry on All Pre-disease Performance Without Restriction; Worst Score=5, Dead.) |
| NCT00056160 (4) [back to overview] | Time to Tumor Progression (TTP) |
| NCT00056160 (4) [back to overview] | Myeloma Response |
| NCT00056160 (4) [back to overview] | Overall Survival |
| NCT00064038 (2) [back to overview] | Progression-Free Survival |
| NCT00064038 (2) [back to overview] | Toxicity |
| NCT00065156 (12) [back to overview] | Participants With Bone Marrow Progression |
| NCT00065156 (12) [back to overview] | Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence |
| NCT00065156 (12) [back to overview] | Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study |
| NCT00065156 (12) [back to overview] | Participant Counts of Platelet Response |
| NCT00065156 (12) [back to overview] | Participant Counts of Cytogenetic Response |
| NCT00065156 (12) [back to overview] | Participants With Adverse Experiences |
| NCT00065156 (12) [back to overview] | Participant Counts of Absolute Neutrophil Count (ANC) Response |
| NCT00065156 (12) [back to overview] | Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study |
| NCT00065156 (12) [back to overview] | Kaplan Meier Estimate for Duration of Transfusion Independence Response |
| NCT00065156 (12) [back to overview] | Time to Transfusion Independence |
| NCT00065156 (12) [back to overview] | Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders |
| NCT00065156 (12) [back to overview] | Participants With Complete or Partial Bone Marrow Improvement |
| NCT00087672 (1) [back to overview] | Efficacy of CC-5013 in Myelofibrosis |
| NCT00091260 (3) [back to overview] | Number of Patients Removed From Study Treatment Due to Toxicities |
| NCT00091260 (3) [back to overview] | Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response |
| NCT00091260 (3) [back to overview] | Number of Patients With Hematologic Response With Single-agent CC-5013 |
| NCT00096044 (6) [back to overview] | Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab |
| NCT00096044 (6) [back to overview] | Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab |
| NCT00096044 (6) [back to overview] | Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months |
| NCT00096044 (6) [back to overview] | Time to Progression for the Combination Therapy of CC-5013+Rituximab |
| NCT00096044 (6) [back to overview] | Number of Participants With Adverse Events on Single Agent CC-5013 |
| NCT00096044 (6) [back to overview] | Time to Progression for Single Agent CC-5013 |
| NCT00098475 (2) [back to overview] | Proportion of Patients With Objective Response (First Phase, Step 2) |
| NCT00098475 (2) [back to overview] | Proportion of Patients With Objective Response (First Phase, Step 1) |
| NCT00109005 (2) [back to overview] | Clinical Responses in Patients With Metastatic Ocular Melanoma |
| NCT00109005 (2) [back to overview] | Number of Participants With Adverse Events |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Brief Pain Inventory (BPI) Total Score at Week 12 |
| NCT00109772 (17) [back to overview] | "Change From Baseline in Mechanically Evoked (Allodynia) Numeric Rating Scale (NRS) Score at Week 12" |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Evening Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in Daily Sleep Assessment Average Score at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score Using Averaged Morning and Evening Readings at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in Activity Level Rating Using a Numeric Rating Scale (NRS) at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in Participant Assessment of CRPS Symptoms Total Score at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Total Score of the Short Form McGill Pain Questionnaire (SF-MPQ) at Week 12 |
| NCT00109772 (17) [back to overview] | Percentage of Participants Who Have a >= 30% Reduction (Improvement) in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score From Baseline to the Last Assessment |
| NCT00109772 (17) [back to overview] | Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period |
| NCT00109772 (17) [back to overview] | Participants Who Had a Change to CRPS Pain Medication During the Treatment Period |
| NCT00109772 (17) [back to overview] | Patient Global Impression of Change (PGIC) at Week 12 |
| NCT00109772 (17) [back to overview] | Difference in Allodynia Rating Between the CRPS-affected Limb and the Normal Limb at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Profile of Mood States (POMS) at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Morning Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Maximal Composite Sensory Nerve Conduction Velocity at Week 12 |
| NCT00109772 (17) [back to overview] | Change From Baseline in the Maximal Composite Motor Nerve Conduction Velocity at Week 12 |
| NCT00112827 (3) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00112827 (3) [back to overview] | Overall Survival |
| NCT00112827 (3) [back to overview] | Number of Subjects With Response |
| NCT00114101 (4) [back to overview] | Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100 |
| NCT00114101 (4) [back to overview] | Number of Participants With Progression, Death or Diagnosis of Second Primary Malignancy |
| NCT00114101 (4) [back to overview] | Overall Survival |
| NCT00114101 (4) [back to overview] | Time to Progression |
| NCT00142168 (4) [back to overview] | Minor Response Rate |
| NCT00142168 (4) [back to overview] | Major Response Rate |
| NCT00142168 (4) [back to overview] | Time to Progression |
| NCT00142168 (4) [back to overview] | Overall Response |
| NCT00179621 (15) [back to overview] | Participants' Response Based on Bone Marrow Samples by the International MDS Working Group (IWG 2000) During Double-blind Period |
| NCT00179621 (15) [back to overview] | Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period |
| NCT00179621 (15) [back to overview] | Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period |
| NCT00179621 (15) [back to overview] | Summary of Participants Who Had Adverse Events (AE) During the Double-blind Period |
| NCT00179621 (15) [back to overview] | Participants Who Progressed to Acute Myeloid Leukemia (AML) During the Study |
| NCT00179621 (15) [back to overview] | Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Week 12 |
| NCT00179621 (15) [back to overview] | Change From Baseline in the Trial Outcome Index-Anemia (TOI-An) Endpoints at Week 12 |
| NCT00179621 (15) [back to overview] | Change From Baseline in the Trial Outcome Index-Fatigue (TOI-F) Endpoints at Week 12 |
| NCT00179621 (15) [back to overview] | Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days |
| NCT00179621 (15) [back to overview] | Kaplan Meier Estimates of Overall Survival by Randomized Group |
| NCT00179621 (15) [back to overview] | Maximum Change From Baseline in Hemoglobin During the Double-blind Period for Participants Who Became Red Blood Cell (RBC) Transfusion Independent for at Least 182 Days |
| NCT00179621 (15) [back to overview] | Participant Count of Deaths During Double-blind and Open-label by Randomized Group |
| NCT00179621 (15) [back to overview] | Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days) |
| NCT00179621 (15) [back to overview] | Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days |
| NCT00179621 (15) [back to overview] | Participants Showing Cytogenetic Response by the International MDS Working Group (IWG 2000) During Double-blind Period as Evaluated by Central Review |
| NCT00179647 (1) [back to overview] | Overall Incidence of Adverse Events |
| NCT00179660 (6) [back to overview] | Duration of Response |
| NCT00179660 (6) [back to overview] | Duration of Tumor Control |
| NCT00179660 (6) [back to overview] | Percentage of Participants With Response |
| NCT00179660 (6) [back to overview] | Percentage of Participants With Tumor Control |
| NCT00179660 (6) [back to overview] | Progression-free Survival |
| NCT00179660 (6) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00179673 (5) [back to overview] | Percentage of Participants With Response |
| NCT00179673 (5) [back to overview] | Percentage of Participants With Tumor Control |
| NCT00179673 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT00179673 (5) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00179673 (5) [back to overview] | The Duration of Response |
| NCT00227591 (1) [back to overview] | Overall Response Rate |
| NCT00238238 (2) [back to overview] | Time to Progression |
| NCT00238238 (2) [back to overview] | Overall Response Rate |
| NCT00267059 (1) [back to overview] | Number of Patients in Overall Response Categories |
| NCT00287287 (1) [back to overview] | Response Rate |
| NCT00294632 (2) [back to overview] | Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab |
| NCT00294632 (2) [back to overview] | Objective Response Rate of Participants Treated With Lenalidomide 20 mg: Overall Response as % of Participants With Complete or Partial Response |
| NCT00348595 (4) [back to overview] | Plasma Concentration of Revilimid at Steady State |
| NCT00348595 (4) [back to overview] | Safety, Feasibility and Tolerance of Revlimid as Assessed by Number of Participants Experiencing Grade 3 and 4 Adverse Events. |
| NCT00348595 (4) [back to overview] | Change in of PSA Slope |
| NCT00348595 (4) [back to overview] | Number of Participants With Prostate-specific Antigen (PSA) Progression |
| NCT00352001 (8) [back to overview] | Time to Transformation to Acute Myeloid Leukemia or Death |
| NCT00352001 (8) [back to overview] | Overall Survival Among Patients With Complete Response |
| NCT00352001 (8) [back to overview] | PHASE I: Maximum Tolerated Dose of Azacitidine |
| NCT00352001 (8) [back to overview] | PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) |
| NCT00352001 (8) [back to overview] | Time to Relapse After Achieving Complete Response |
| NCT00352001 (8) [back to overview] | PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) |
| NCT00352001 (8) [back to overview] | Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events |
| NCT00352001 (8) [back to overview] | PHASE I: Maximum Tolerated Dose of Lenalidomide |
| NCT00352365 (4) [back to overview] | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug |
| NCT00352365 (4) [back to overview] | Total Response |
| NCT00352365 (4) [back to overview] | Cytogenetic Abnormalities |
| NCT00352365 (4) [back to overview] | Complete Response |
| NCT00352794 (1) [back to overview] | Number of Patients With Objective Response (Complete and Partial Response + Hematological Improvement) |
| NCT00360672 (1) [back to overview] | Number of Participants With a Response (Complete Remissions (CR), Complete Remissions With Incomplete Platelet Recovery [CRp] and Partial Responses) |
| NCT00378105 (4) [back to overview] | Objective Response Rate of the Drug Combination in This Patient Populations. |
| NCT00378105 (4) [back to overview] | Estimated 18-month Overall Survival Rate |
| NCT00378105 (4) [back to overview] | Percentage of Patients Who Remained in Response for More Than 18 Months |
| NCT00378105 (4) [back to overview] | Estimated 18-month Progression Free Survival (PFS) Rate |
| NCT00378209 (5) [back to overview] | Overall Survival |
| NCT00378209 (5) [back to overview] | The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months |
| NCT00378209 (5) [back to overview] | Duration of Response |
| NCT00378209 (5) [back to overview] | Objective Response Rate |
| NCT00378209 (5) [back to overview] | Progression Free Survival |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale |
| NCT00405756 (28) [back to overview] | Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period |
| NCT00405756 (28) [back to overview] | Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC) |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC) |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates for Time to Next Antimyeloma Therapy |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates of Overall Survival (OS) |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC) |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale |
| NCT00405756 (28) [back to overview] | Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC) |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale |
| NCT00405756 (28) [back to overview] | Time to First Response |
| NCT00405756 (28) [back to overview] | Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale |
| NCT00410605 (5) [back to overview] | Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bevacizumab and Lenalidomide |
| NCT00410605 (5) [back to overview] | Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline |
| NCT00410605 (5) [back to overview] | Toxicity and Tolerability of the Bevacizumab and Lenalidomide Combination |
| NCT00410605 (5) [back to overview] | Progression Free Survival (Time to Progression) |
| NCT00410605 (5) [back to overview] | Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline |
| NCT00413036 (4) [back to overview] | Progression-free Survival as Determined by Central Review |
| NCT00413036 (4) [back to overview] | Duration of Response as Determined by Central Review |
| NCT00413036 (4) [back to overview] | Participants Categorized by Best Response as Determined by Central Review |
| NCT00413036 (4) [back to overview] | Time to Progression as Determined by Central Review |
| NCT00420849 (24) [back to overview] | Time to First Venous Thromboembolic Treatment-Emergent Adverse Event (TEAE) |
| NCT00420849 (24) [back to overview] | Time to First Peripheral Neuropathy Treatment-Emergent Adverse Event (TEAE) |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea/Vomiting Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhea Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Cognitive Functioning Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale |
| NCT00420849 (24) [back to overview] | Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Problems Scale |
| NCT00420849 (24) [back to overview] | Participants With Adverse Events of Special Interest: Venous Thromboembolic Events |
| NCT00420849 (24) [back to overview] | Participants With Adverse Events of Special Interest: Peripheral Neuropathy |
| NCT00420849 (24) [back to overview] | Overall Incidence of Treatment-emergent Adverse Events (TEAEs), by Severity, Seriousness, and Relationship to Treatment |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Duration of Response |
| NCT00424047 (12) [back to overview] | Time to First Symptomatic Skeletal-related Event (SRE) (Clinical Need for Radiation or Surgery to Bone) |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008) |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008) |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008) |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Time to Tumor Progression (TTP) |
| NCT00424047 (12) [back to overview] | Number of Participants With Adverse Events (AE) |
| NCT00424047 (12) [back to overview] | Kaplan-Meier Estimate of Overall Survival (OS) |
| NCT00424047 (12) [back to overview] | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale |
| NCT00424047 (12) [back to overview] | Time to First Worsening on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Later Cut-off Date of 02 March 2008) |
| NCT00424047 (12) [back to overview] | Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008) |
| NCT00424047 (12) [back to overview] | Summary of Myeloma Response Rates Based on Best Response Assessment |
| NCT00439231 (1) [back to overview] | To Establish the Overall Response Rate Measured at 24 Weeks After First Dose of Lenalidomide Using This Dosing Regimen |
| NCT00445484 (4) [back to overview] | 6B Antibody Response to Prevnar Vaccine in Peripheral Blood |
| NCT00445484 (4) [back to overview] | 14F Antibody Response to Prevnar Vaccine in Peripheral Blood |
| NCT00445484 (4) [back to overview] | 19F Antibody Response to Prevnar Vaccine in Peripheral Blood |
| NCT00445484 (4) [back to overview] | 23F Antibody Response to Prevnar Vaccine in Peripheral Blood |
| NCT00445692 (2) [back to overview] | Time to Disease Progression |
| NCT00445692 (2) [back to overview] | Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 |
| NCT00460031 (5) [back to overview] | Ratio of Change in Immune Response From Baseline |
| NCT00460031 (5) [back to overview] | Change in Immune Response From Baseline |
| NCT00460031 (5) [back to overview] | Time to Progression |
| NCT00460031 (5) [back to overview] | Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease |
| NCT00460031 (5) [back to overview] | Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0 |
| NCT00466921 (4) [back to overview] | Response to Treatment |
| NCT00466921 (4) [back to overview] | Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 |
| NCT00466921 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT00466921 (4) [back to overview] | Duration of Response (DOR) |
| NCT00477750 (5) [back to overview] | Overall Survival (OS) at 3 Years |
| NCT00477750 (5) [back to overview] | Duration of Response (DOR) |
| NCT00477750 (5) [back to overview] | Progression-free Survival |
| NCT00477750 (5) [back to overview] | Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) |
| NCT00477750 (5) [back to overview] | Patients With Overall Confirmed Response |
| NCT00478218 (4) [back to overview] | Overall Survival (OS) |
| NCT00478218 (4) [back to overview] | Duration of Response (DOR) |
| NCT00478218 (4) [back to overview] | Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment |
| NCT00478218 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT00478777 (3) [back to overview] | Participants With Treatment-emergent Adverse Experiences (TEAEs) |
| NCT00478777 (3) [back to overview] | Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria |
| NCT00478777 (3) [back to overview] | Kaplan Meier Estimate for Time to Disease Progression |
| NCT00482911 (2) [back to overview] | Response Rate (Complete and Partial Response) |
| NCT00482911 (2) [back to overview] | Toxicity |
| NCT00507442 (11) [back to overview] | Number of Patients With Stringent Complete Response Rate |
| NCT00507442 (11) [back to overview] | Overall Survival |
| NCT00507442 (11) [back to overview] | Probability of 1-year Survival |
| NCT00507442 (11) [back to overview] | Number of Patients With Combined Complete Response and Very Good Partial Response |
| NCT00507442 (11) [back to overview] | Time to Disease Progression |
| NCT00507442 (11) [back to overview] | Time to Response |
| NCT00507442 (11) [back to overview] | Progression-free Survival |
| NCT00507442 (11) [back to overview] | Duration of Response |
| NCT00507442 (11) [back to overview] | Number of Patients With Adverse Events (AEs) |
| NCT00507442 (11) [back to overview] | Number of Patients With Complete Response Rate + Near Complete Response Rate |
| NCT00507442 (11) [back to overview] | Number of Patients With Overall Response |
| NCT00522392 (4) [back to overview] | Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR]) |
| NCT00522392 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT00522392 (4) [back to overview] | Overall Survival (OS) |
| NCT00522392 (4) [back to overview] | Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) |
| NCT00535873 (1) [back to overview] | Overall Response Rate (ORR) |
| NCT00536341 (4) [back to overview] | Complete Response Rate |
| NCT00536341 (4) [back to overview] | Overall Survival |
| NCT00536341 (4) [back to overview] | Number of Adverse Events as a Measure of Safety and Tolerability |
| NCT00536341 (4) [back to overview] | Progression-Free Survival |
| NCT00538733 (4) [back to overview] | Effect of Drug Combination on Multiple Myeloma |
| NCT00538733 (4) [back to overview] | Progression Free Survival |
| NCT00538733 (4) [back to overview] | Median Time to Maximum Response |
| NCT00538733 (4) [back to overview] | Event Free Survival |
| NCT00538824 (1) [back to overview] | Effect of Drug Combination on Multiple Myeloma |
| NCT00540007 (8) [back to overview] | Relapse Free Survival (RFS) |
| NCT00540007 (8) [back to overview] | Safety and Tolerability of Lenalidomide Therapy as Measured by the Number of Participants Who Experience Each Adverse Event (Grade 3 or 4 Adverse Events Only) Refractory cHL. |
| NCT00540007 (8) [back to overview] | Time to Progression (TTP). |
| NCT00540007 (8) [back to overview] | Duration of Response |
| NCT00540007 (8) [back to overview] | Cytostatic Overall Response Rate |
| NCT00540007 (8) [back to overview] | Event Free Survival (EFS). |
| NCT00540007 (8) [back to overview] | Overall Survival (OS) |
| NCT00540007 (8) [back to overview] | Objective Overall Response Rate (ORR) in Relapsed or Refractory cHL. |
| NCT00540644 (3) [back to overview] | Quality of Life Using the FACT-G Data |
| NCT00540644 (3) [back to overview] | Response Rate (RR) After 6 Cycles of Therapy Using the Proposed International Myeloma Working Group Uniform Response Criteria |
| NCT00540644 (3) [back to overview] | Treatment Related Adverse Events Grade 3 or Higher |
| NCT00546897 (12) [back to overview] | Duration of CR for Complete Responders |
| NCT00546897 (12) [back to overview] | CR With Complete Blood Counts (CRi) Rate |
| NCT00546897 (12) [back to overview] | Response Rate (RR) |
| NCT00546897 (12) [back to overview] | Morphologic Leukemia Free State |
| NCT00546897 (12) [back to overview] | Morphologic Complete Remission Rate (CRm) |
| NCT00546897 (12) [back to overview] | Safety and Tolerability (Removal From Study Due to Adverse Events) |
| NCT00546897 (12) [back to overview] | Relapse Free Survival (RFS) for Complete Responders |
| NCT00546897 (12) [back to overview] | Progression-free Survival |
| NCT00546897 (12) [back to overview] | Partial Remission Rate (PR) |
| NCT00546897 (12) [back to overview] | Overall Survival (OS) |
| NCT00546897 (12) [back to overview] | Complete Remission Rate (CRm + CRi + CRc) |
| NCT00546897 (12) [back to overview] | Cytogenetics CR Rate (CRc) |
| NCT00553644 (4) [back to overview] | Number of Participants With an Overall Response Defined as Complete Response and Partial Response |
| NCT00553644 (4) [back to overview] | Time to Progression |
| NCT00553644 (4) [back to overview] | Overall Survival |
| NCT00553644 (4) [back to overview] | Incidence of Adverse Events |
| NCT00560391 (10) [back to overview] | Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone |
| NCT00560391 (10) [back to overview] | Number of Participants With Dose-limiting Toxicity (DLT) |
| NCT00560391 (10) [back to overview] | Number of Participants With Minimal Response |
| NCT00560391 (10) [back to overview] | Number of Participants With Partial Response |
| NCT00560391 (10) [back to overview] | Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation |
| NCT00560391 (10) [back to overview] | Number of Participants With Complete Response and Very Good Partial Response |
| NCT00560391 (10) [back to overview] | Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin (TB), and Serum Creatinine (SC) |
| NCT00560391 (10) [back to overview] | Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus |
| NCT00560391 (10) [back to overview] | Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone) |
| NCT00560391 (10) [back to overview] | Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia |
| NCT00564889 (5) [back to overview] | Number of Patients With Organ Response |
| NCT00564889 (5) [back to overview] | Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) |
| NCT00564889 (5) [back to overview] | Number of Participants With Severe Adverse Events |
| NCT00564889 (5) [back to overview] | Overall Survival (OS) |
| NCT00564889 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT00567229 (1) [back to overview] | Final Response Rate After 4 Courses of Treatment |
| NCT00602459 (6) [back to overview] | Overall Response Rate in Patients Without Del(11q22.3) |
| NCT00602459 (6) [back to overview] | Overall Response Rates in Patients With Del(11q22.3) |
| NCT00602459 (6) [back to overview] | PFS Rate of Patients With Del(11q22.3) |
| NCT00602459 (6) [back to overview] | Time-to-progression in Patients With Del(11q22.3) |
| NCT00602459 (6) [back to overview] | Time-to-progression in Patients Without Del(11q22.3) |
| NCT00602459 (6) [back to overview] | 2-Year Progression Free Survival (PFS) Rate |
| NCT00602641 (4) [back to overview] | Change in Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) Score From Baseline to Cycle 12 |
| NCT00602641 (4) [back to overview] | Overall Survival |
| NCT00602641 (4) [back to overview] | Very Good Partial Response (VGPR) Rate |
| NCT00602641 (4) [back to overview] | Progression-Free Survival (PFS) |
| NCT00602836 (6) [back to overview] | Overall Survival (OS) |
| NCT00602836 (6) [back to overview] | Treatment Free Survival (TFS) |
| NCT00602836 (6) [back to overview] | Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide |
| NCT00602836 (6) [back to overview] | Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide |
| NCT00602836 (6) [back to overview] | Number of Participants With a Response (CR, nPR, PR) |
| NCT00602836 (6) [back to overview] | Number of Participants With Complete Response (CR) |
| NCT00603447 (2) [back to overview] | Number of Participants With Dose-limiting Toxicities |
| NCT00603447 (2) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00609869 (3) [back to overview] | Clinical Benefit Rate |
| NCT00609869 (3) [back to overview] | Median Time to Treatment Failure (TTF) |
| NCT00609869 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT00617591 (5) [back to overview] | Median Progression Free Survival (PFS) in Months |
| NCT00617591 (5) [back to overview] | Overall Response Rate (ORR) - Percentage of Participants With Partial Response or Better With Induction Regimen |
| NCT00617591 (5) [back to overview] | Percentage of Participants With Very Good Partial Remission (VGPR) or Better |
| NCT00617591 (5) [back to overview] | Occurrence of Induction Toxicities |
| NCT00617591 (5) [back to overview] | 2 Year Overall Survival (OS) Rate |
| NCT00619684 (6) [back to overview] | Number of Patients Who Experience Improvement in GVHD on Lenalidomide, Defined as the Reduction in Severity of GVHD as Defined by the National Institutes of Health (NIH) Consensus Criteria |
| NCT00619684 (6) [back to overview] | Response Rate, Defined as the Number of Patients Achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR) |
| NCT00619684 (6) [back to overview] | Overall Survival |
| NCT00619684 (6) [back to overview] | Adverse Events, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 |
| NCT00619684 (6) [back to overview] | TTP |
| NCT00619684 (6) [back to overview] | Number of Patients Requiring Dose Interruption, Dose Reduction or Discontinuance of Lenalidomide |
| NCT00622336 (2) [back to overview] | Number of Participants With Adverse Events (AE) During the Extension Phase |
| NCT00622336 (2) [back to overview] | Number of Participants With Adverse Events (AE) During the Treatment Phase |
| NCT00632359 (3) [back to overview] | Time to Progression |
| NCT00632359 (3) [back to overview] | Response Assessments: Disease Status at the End of Lenalidomide Consolidation Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Response Criteria |
| NCT00632359 (3) [back to overview] | Improvement in Quality of Remission: Number of Participants With Response Versus No Response by NCI Working Group Criteria Disease Status Change at Start/End of Lenalidomide Consolidation |
| NCT00633594 (12) [back to overview] | Incidence of Non-Serious Adverse Events as a Measure of Safety and Tolerability, Phase II |
| NCT00633594 (12) [back to overview] | Duration of Response (DoR) of Phase I and Phase II Participants |
| NCT00633594 (12) [back to overview] | Duration of Response (DoR) of Previously Treated and Previously Untreated Participants |
| NCT00633594 (12) [back to overview] | Maximum Tolerated Dose of Lenalidomide Combined With Bortezomib and Rituximab in Phase I Participants |
| NCT00633594 (12) [back to overview] | Overall Response Rate (ORR) of Phase I and Phase II Participants |
| NCT00633594 (12) [back to overview] | Overall Response Rate (ORR) of Previously Treated and Previously Untreated Participants |
| NCT00633594 (12) [back to overview] | Overall Survival of Phase I and Phase II Participants |
| NCT00633594 (12) [back to overview] | Overall Survival of Previously Treated and Previously Untreated Participants |
| NCT00633594 (12) [back to overview] | Time to Best Response of Previously Treated and Previously Untreated Participants |
| NCT00633594 (12) [back to overview] | Progression Free Survival (PFS) of Previously Treated and Previously Untreated Participants |
| NCT00633594 (12) [back to overview] | Time to Best Response of Phase I and Phase II Participants |
| NCT00633594 (12) [back to overview] | Progression Free Survival (PFS) of Phase I and Phase II Participants |
| NCT00633945 (9) [back to overview] | Skindex Function |
| NCT00633945 (9) [back to overview] | Patient General Assessment (PtGA) for Skin |
| NCT00633945 (9) [back to overview] | Pain in Skin |
| NCT00633945 (9) [back to overview] | Number of Participants With Change in IFN and CD4 Levels at 6 Weeks |
| NCT00633945 (9) [back to overview] | Fatigue |
| NCT00633945 (9) [back to overview] | Cutaneous Lupus Area and Severity Index (CLASI) |
| NCT00633945 (9) [back to overview] | Itch in Skin |
| NCT00633945 (9) [back to overview] | Skindex Symptoms |
| NCT00633945 (9) [back to overview] | Physician Global Assessment (PGA) for Skin |
| NCT00642954 (3) [back to overview] | Number of Participants Experiencing Best Overall Response Determined by Complete Response (CR), Near Complete Response (NCR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD) |
| NCT00642954 (3) [back to overview] | Number of Participants Experiencing Drug-Related Adverse Events (AEs) |
| NCT00642954 (3) [back to overview] | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) |
| NCT00644228 (3) [back to overview] | Response Rates () |
| NCT00644228 (3) [back to overview] | Progression-free Survival |
| NCT00644228 (3) [back to overview] | Overall Survival |
| NCT00654186 (3) [back to overview] | Number of Participants With Overall Clinical Benefit (OCB), Defined as the Sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Divided by the Number of Participants |
| NCT00654186 (3) [back to overview] | Time to PSA Progression |
| NCT00654186 (3) [back to overview] | Time to Disesase Progression as Measured by Radiographic Progression |
| NCT00655668 (4) [back to overview] | Progression-Free Survival |
| NCT00655668 (4) [back to overview] | Duration of Response |
| NCT00655668 (4) [back to overview] | Participants Categorized by Best Response as Determined by Investigator |
| NCT00655668 (4) [back to overview] | Safety |
| NCT00665652 (1) [back to overview] | Change in Total Neuropathy Score in Subjects With MGUS Associated Neuropathy After Treatment With Lenalidomide. |
| NCT00670358 (3) [back to overview] | Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3) |
| NCT00670358 (3) [back to overview] | Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite) |
| NCT00670358 (3) [back to overview] | Toxicity as Assessed by NCI CTCAE v3.0 (Phase I) |
| NCT00675441 (1) [back to overview] | Number of Participants' With Treatment Response of Complete or Partial Response |
| NCT00679367 (3) [back to overview] | Number of Participants With Hematologic Response |
| NCT00679367 (3) [back to overview] | Number of Participants Removed From Study Due to Toxicities |
| NCT00679367 (3) [back to overview] | Number of Organs Improved or Stable Based on Description Below: |
| NCT00684242 (1) [back to overview] | Change in Cancer Pain Intensity Determined by Edmonton Symptom Assessment Scale (ESAS) |
| NCT00687674 (1) [back to overview] | Number of Participants With a Grade 3 and 4 Adverse Event (Phase I) |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Constipation Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT) |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Insomnia Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Pain Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain |
| NCT00689936 (43) [back to overview] | Time to First Response Based on the Review by the IRAC |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain |
| NCT00689936 (43) [back to overview] | Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review |
| NCT00689936 (43) [back to overview] | Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review |
| NCT00689936 (43) [back to overview] | Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review. |
| NCT00689936 (43) [back to overview] | Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC) |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale |
| NCT00689936 (43) [back to overview] | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score |
| NCT00689936 (43) [back to overview] | Number of Participants With Adverse Events (AEs) During the Active Treatment Phase |
| NCT00689936 (43) [back to overview] | Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase |
| NCT00689936 (43) [back to overview] | Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase |
| NCT00689936 (43) [back to overview] | Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS) |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Time to Treatment Failure (TTF) |
| NCT00689936 (43) [back to overview] | Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain |
| NCT00689936 (43) [back to overview] | Time to First Response Based on the Investigator Assessment at the Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Percentage of Participants With an Objective Response Based on IRAC Review |
| NCT00689936 (43) [back to overview] | Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain |
| NCT00689936 (43) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain |
| NCT00691704 (5) [back to overview] | Time to Response |
| NCT00691704 (5) [back to overview] | Progression Free Survival |
| NCT00691704 (5) [back to overview] | Time to Progression |
| NCT00691704 (5) [back to overview] | Overall Survival |
| NCT00691704 (5) [back to overview] | Duration of Response |
| NCT00695786 (1) [back to overview] | Number of Participants With Best Overall Disease Response |
| NCT00717756 (1) [back to overview] | Response Rate by Recist Criteria |
| NCT00724568 (2) [back to overview] | Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) |
| NCT00724568 (2) [back to overview] | The Percentage of Patients That Achieved Partial or Complete Response to Treatment. |
| NCT00727415 (6) [back to overview] | Number of Patients With Severe Infections |
| NCT00727415 (6) [back to overview] | Overall Complete Response (CR) Rate (Phase II) |
| NCT00727415 (6) [back to overview] | Maximum Tolerated Dose of Lenalidomide (Phase I) |
| NCT00727415 (6) [back to overview] | Toxicity as Assessed by NCI CTCAE v3.0 |
| NCT00727415 (6) [back to overview] | Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.). |
| NCT00727415 (6) [back to overview] | Number of Patients Reaching Disease-free Survival (DSF) Overall |
| NCT00737529 (11) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
| NCT00737529 (11) [back to overview] | Time to Complete Response (CR+CRu) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Time to Response (TTR) |
| NCT00737529 (11) [back to overview] | Overall Survival (OS) |
| NCT00737529 (11) [back to overview] | Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Kaplan Meier Estimate of Duration of Response (DoR) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee |
| NCT00737529 (11) [back to overview] | Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC) |
| NCT00742560 (12) [back to overview] | Progression-free Survival (PFS) |
| NCT00742560 (12) [back to overview] | Time to Progression (TTP) |
| NCT00742560 (12) [back to overview] | Mean Serum Concentrations of Elotuzumab During Cycle 1 |
| NCT00742560 (12) [back to overview] | Mean Serum Concentrations of Elotuzumab During Cycle 1 |
| NCT00742560 (12) [back to overview] | Number of Participants With Infusion Reactions |
| NCT00742560 (12) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
| NCT00742560 (12) [back to overview] | Plasma Cell Myeloma Cytogenetic Subtype |
| NCT00742560 (12) [back to overview] | Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1) |
| NCT00742560 (12) [back to overview] | Duration of Response |
| NCT00742560 (12) [back to overview] | Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 1) |
| NCT00742560 (12) [back to overview] | Percentage of Participants With Treatment-emergent Anti-elotuzumab Antibody (ADA) |
| NCT00742560 (12) [back to overview] | Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 2) |
| NCT00751296 (2) [back to overview] | Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS). |
| NCT00751296 (2) [back to overview] | To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL) |
| NCT00759603 (1) [back to overview] | Overall Participant Response Rate: Percentage of Participants With Complete + Partial Response According to Revised National Cancer Institute-sponsored Working Group Guidelines |
| NCT00765245 (3) [back to overview] | Number of Patients With Each Worst-Grade Toxicity |
| NCT00765245 (3) [back to overview] | Disease-free Survival at 2 Years |
| NCT00765245 (3) [back to overview] | Disease-free Survival at 1 Year |
| NCT00772915 (5) [back to overview] | Progression-free Survival (PFS) Rate at 12 Months |
| NCT00772915 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT00772915 (5) [back to overview] | Overall Survival (OS) |
| NCT00772915 (5) [back to overview] | Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity) |
| NCT00772915 (5) [back to overview] | Confirmed Response Rate |
| NCT00774345 (3) [back to overview] | Overall Survival (OS) |
| NCT00774345 (3) [back to overview] | Progression Free Survival 2 (PFS2) |
| NCT00774345 (3) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00783367 (2) [back to overview] | Time Until Progression After Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphomas With Rituximab Resistance |
| NCT00783367 (2) [back to overview] | Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance |
| NCT00784927 (5) [back to overview] | Assessment of Tumor Response |
| NCT00784927 (5) [back to overview] | Progression-free Survival Time |
| NCT00784927 (5) [back to overview] | Survival Time |
| NCT00784927 (5) [back to overview] | Time to Treatment Failure |
| NCT00784927 (5) [back to overview] | Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia). |
| NCT00790842 (6) [back to overview] | Progression-free Survival |
| NCT00790842 (6) [back to overview] | Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR] |
| NCT00790842 (6) [back to overview] | Overall Survival Time |
| NCT00790842 (6) [back to overview] | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient |
| NCT00790842 (6) [back to overview] | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy |
| NCT00790842 (6) [back to overview] | Duration of Response |
| NCT00792077 (4) [back to overview] | ECOG Performance Status |
| NCT00792077 (4) [back to overview] | The Functional Assessment of Chronic Illness Therapy-Fatigue Subscale Score |
| NCT00792077 (4) [back to overview] | Total Sleep Time as Measured by Polysomnography (PSG) |
| NCT00792077 (4) [back to overview] | Epwort Sleep Scale |
| NCT00807599 (2) [back to overview] | Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma. |
| NCT00807599 (2) [back to overview] | Overall Survival |
| NCT00812968 (19) [back to overview] | Number of Participants With Adverse Events (AE) |
| NCT00812968 (19) [back to overview] | Percentage of Bone Marrow Myeloblasts |
| NCT00812968 (19) [back to overview] | Change From Baseline in Percentage of Bone Marrow Erythroblasts |
| NCT00812968 (19) [back to overview] | Percentage of Bone Marrow Promyelocytes |
| NCT00812968 (19) [back to overview] | Time to Erythroid Response |
| NCT00812968 (19) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Change From Baseline in Hemoglobin Concentration |
| NCT00812968 (19) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Terminal Half-life (T1/2) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Time to Maximum Plasma Concentration (Tmax) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Number of Participants With a Erythroid Response |
| NCT00812968 (19) [back to overview] | Duration of Erythroid Response |
| NCT00812968 (19) [back to overview] | Number of Participants With a Cytogenetic Response |
| NCT00812968 (19) [back to overview] | Apparent Terminal Elimination Rate Constant of Lenalidomide |
| NCT00812968 (19) [back to overview] | Number of Participants With a Neutrophil Response |
| NCT00812968 (19) [back to overview] | Apparent Total Plasma Clearance (CL/F) of Lenalidomide |
| NCT00812968 (19) [back to overview] | Apparent Volume of Distribution (VzF) of Lenalidomide |
| NCT00831766 (5) [back to overview] | Median Overall Survival (OS) |
| NCT00831766 (5) [back to overview] | Rate of Lenalidomide Related Toxicity During Maintenance Therapy |
| NCT00831766 (5) [back to overview] | Median Progression-Free Survival (PFS) |
| NCT00831766 (5) [back to overview] | Phase I: Recommended Phase II Dose |
| NCT00831766 (5) [back to overview] | Phase II: Complete Response Rate of Participants Treated at Maximum Tolerated Dose (MTD) |
| NCT00837031 (3) [back to overview] | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease |
| NCT00837031 (3) [back to overview] | Six-Month Overall Survival (OS) Probability, the Percentage of Patients Estimated to be Alive Six Months After Beginning Protocol Treatment |
| NCT00837031 (3) [back to overview] | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death |
| NCT00843882 (9) [back to overview] | Time to Major Erythroid Response (MER) |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Minor Erythroid Response |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Major Erythroid Response (MER) |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Cytogenetic Response |
| NCT00843882 (9) [back to overview] | Proportion of Patients With Bone Marrow Response |
| NCT00843882 (9) [back to overview] | Pretreatment Endogenous Erythropoietin Level |
| NCT00843882 (9) [back to overview] | Duration of Major Erythroid Response (MER) |
| NCT00860457 (1) [back to overview] | Complete Response Rate |
| NCT00867308 (2) [back to overview] | Response Rate |
| NCT00867308 (2) [back to overview] | Grade 3-4 Toxicity |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Constipation |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain |
| NCT00875667 (47) [back to overview] | Number of Participants With Treatment Emergent Adverse Events |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to Progression According to the IRC Central Review |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator |
| NCT00875667 (47) [back to overview] | Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit |
| NCT00875667 (47) [back to overview] | Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit |
| NCT00890552 (4) [back to overview] | Event-free Survival (EFS) |
| NCT00890552 (4) [back to overview] | Duration of Response |
| NCT00890552 (4) [back to overview] | Overall Survival (OS) |
| NCT00890552 (4) [back to overview] | Hematologic Response Rate |
| NCT00890929 (9) [back to overview] | Time to CR |
| NCT00890929 (9) [back to overview] | Maximum Tolerated Dose (MTD) of Lenalidomide |
| NCT00890929 (9) [back to overview] | Remission Duration |
| NCT00890929 (9) [back to overview] | OS of Responders |
| NCT00890929 (9) [back to overview] | Overall Response Rate (ORR) |
| NCT00890929 (9) [back to overview] | Overall Survival (OS) |
| NCT00890929 (9) [back to overview] | 4-week Survival Rate |
| NCT00890929 (9) [back to overview] | Compete Remission (CR) Rate |
| NCT00890929 (9) [back to overview] | Time to PR |
| NCT00899431 (1) [back to overview] | Percentage of Participants With GVHD (Graft Versus Host Disease) |
| NCT00903630 (5) [back to overview] | Phase 2 - Number of Subjects Who Are Progression-Free and Alive |
| NCT00903630 (5) [back to overview] | Phase 1 - Maximum Tolerated Dose (MTD) of Lenalidomide When Combined With Fixed Dose Liposomal Doxorubicin in Women With Recurrent Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer |
| NCT00903630 (5) [back to overview] | Phase 1 - Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) |
| NCT00903630 (5) [back to overview] | Phase 2 - Number of Subjects Achieving a Partial or Complete Response |
| NCT00903630 (5) [back to overview] | Phase 2 - Number of Subjects Who Are Progression-Free and Alive |
| NCT00908232 (6) [back to overview] | Overall Survival |
| NCT00908232 (6) [back to overview] | Time to Progression |
| NCT00908232 (6) [back to overview] | Progression Free Survival |
| NCT00908232 (6) [back to overview] | Median Time to First Confirmed Response |
| NCT00908232 (6) [back to overview] | One Year Survival |
| NCT00908232 (6) [back to overview] | Overall Best Confirmed Response |
| NCT00910858 (10) [back to overview] | PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide |
| NCT00910858 (10) [back to overview] | Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide |
| NCT00910858 (10) [back to overview] | Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) |
| NCT00910858 (10) [back to overview] | Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level |
| NCT00910858 (10) [back to overview] | Percentage of Participants With a Erythroid Response Across All Phases |
| NCT00910858 (10) [back to overview] | PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax) |
| NCT00910858 (10) [back to overview] | PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose |
| NCT00910858 (10) [back to overview] | PK Phase: Terminal Half-life (t1/2) |
| NCT00910858 (10) [back to overview] | Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose |
| NCT00910858 (10) [back to overview] | Time to Grade 4 Neutropenia or Thrombocytopenia |
| NCT00910910 (14) [back to overview] | Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014 |
| NCT00910910 (14) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00910910 (14) [back to overview] | Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment |
| NCT00910910 (14) [back to overview] | Time to Response |
| NCT00910910 (14) [back to overview] | Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines |
| NCT00910910 (14) [back to overview] | Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014 |
| NCT00910910 (14) [back to overview] | Kaplan Meier Estimate of Overall Survival |
| NCT00910910 (14) [back to overview] | Kaplan-Meier Estimate for Duration of Response |
| NCT00910910 (14) [back to overview] | Time to Response for a Later Cut-off Date of 31 March 2014 |
| NCT00910910 (14) [back to overview] | Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014 |
| NCT00910910 (14) [back to overview] | Kaplan-Meier Estimate of Progression Free Survival (PFS) |
| NCT00910910 (14) [back to overview] | Kaplan Meier Estimate for Overall Survival at the Final Analysis |
| NCT00910910 (14) [back to overview] | Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014 |
| NCT00910910 (14) [back to overview] | Number of Participants Deaths During the Treatment and Survival Follow-Up Phase |
| NCT00928486 (3) [back to overview] | Kaplan-Meier Estimates of Duration of Response (DoR) |
| NCT00928486 (3) [back to overview] | Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) |
| NCT00928486 (3) [back to overview] | Myeloma Response Rate |
| NCT00939510 (3) [back to overview] | RECIST-defined Measurable Disease |
| NCT00939510 (3) [back to overview] | Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study |
| NCT00939510 (3) [back to overview] | Number of Patients With a PSA Response |
| NCT00942578 (10) [back to overview] | Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination |
| NCT00942578 (10) [back to overview] | Count of Participants With a Radiologic Response |
| NCT00942578 (10) [back to overview] | Recommended Phase 2 Dose (RP2D) |
| NCT00942578 (10) [back to overview] | Median Time to Progression (TTP) |
| NCT00942578 (10) [back to overview] | Median Overall Survival of Patients Studied |
| NCT00942578 (10) [back to overview] | Count of Participants With Dose-Limiting Toxicities (DLT) |
| NCT00942578 (10) [back to overview] | Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells |
| NCT00942578 (10) [back to overview] | Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells |
| NCT00942578 (10) [back to overview] | Count of Participants With Prostatic Antigen-Specific (PSA) Declines |
| NCT00942578 (10) [back to overview] | Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration |
| NCT00963105 (8) [back to overview] | Overall Response Rate (ORR) |
| NCT00963105 (8) [back to overview] | Kaplan-Meier Estimate of Progression Free Survival |
| NCT00963105 (8) [back to overview] | Kaplan-Meier Estimate of Event-Free Survival |
| NCT00963105 (8) [back to overview] | Kaplan-Meier Estimate of Duration of Response |
| NCT00963105 (8) [back to overview] | Kaplan-Meier Estimate of Time to Progression |
| NCT00963105 (8) [back to overview] | Kaplan-Meier Estimate of Overall Survival |
| NCT00963105 (8) [back to overview] | Number of Participants With Treatment-emergent Adverse Events |
| NCT00963105 (8) [back to overview] | Time to Response |
| NCT00966693 (7) [back to overview] | Complete Response(CR) and Very Good Partial Response(VGPR) |
| NCT00966693 (7) [back to overview] | Incidence of Adverse Events |
| NCT00966693 (7) [back to overview] | Progression Free Survival |
| NCT00966693 (7) [back to overview] | Number of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM) |
| NCT00966693 (7) [back to overview] | Time to Best Response |
| NCT00966693 (7) [back to overview] | Time to Progression |
| NCT00966693 (7) [back to overview] | Time to Next Therapy |
| NCT00974233 (5) [back to overview] | Progression Free Survival |
| NCT00974233 (5) [back to overview] | Overall Survival |
| NCT00974233 (5) [back to overview] | Toxicities Observed With Induction Chemotherapy and Maintenance Therapy |
| NCT00974233 (5) [back to overview] | Progression-free Survival |
| NCT00974233 (5) [back to overview] | Objective Response Rate (Complete + Partial Responses) |
| NCT00975806 (3) [back to overview] | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Lenalidomide and Sunitinib |
| NCT00975806 (3) [back to overview] | Phase 1 : Tumor Response Rate According to RECIST 1.1 |
| NCT00975806 (3) [back to overview] | Phase 1: Maximum Tolerated Dose (MTD) |
| NCT00988208 (7) [back to overview] | Progression-Free Survival (PFS) |
| NCT00988208 (7) [back to overview] | Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria |
| NCT00988208 (7) [back to overview] | Percentage of Participants Who Received Post-Study Therapies |
| NCT00988208 (7) [back to overview] | Overall Survival (OS) |
| NCT00988208 (7) [back to overview] | Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial |
| NCT00988208 (7) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (AEs) |
| NCT00988208 (7) [back to overview] | Time to Onset of Secondary Primary Malignancies |
| NCT00996931 (2) [back to overview] | Change in Childhood Autism Rating Scale (CARS)Value From Baseline to 6 Weeks |
| NCT00996931 (2) [back to overview] | Change in TNF-alpha Levels |
| NCT01002755 (3) [back to overview] | Overall Response Rate |
| NCT01002755 (3) [back to overview] | Number of Participants With Tolerance of the Medication Combination |
| NCT01002755 (3) [back to overview] | Progression Free Survival |
| NCT01011894 (1) [back to overview] | Best Response |
| NCT01016600 (15) [back to overview] | Morphologic Leukemia-free State |
| NCT01016600 (15) [back to overview] | Partial Remission Rate (PR) |
| NCT01016600 (15) [back to overview] | Phase I Only - Maximum Tolerated Dose (MTD) as Measured by Dose-limiting Toxicities (DLTs) |
| NCT01016600 (15) [back to overview] | Phase II Only - Complete Remission Rate (CRm + CRi) in Participants With Untreated AML ≥60 Years of Age |
| NCT01016600 (15) [back to overview] | Phase I Only - Maximum Tolerated Dose (MTD) |
| NCT01016600 (15) [back to overview] | Relapse Free Survival (RFS) |
| NCT01016600 (15) [back to overview] | Time to Progression (TTP) |
| NCT01016600 (15) [back to overview] | Response Rate (CRm + CRc + CRi + PR) |
| NCT01016600 (15) [back to overview] | Toxicity Profile (Grade 3/4 Toxicities) |
| NCT01016600 (15) [back to overview] | Overall Survival |
| NCT01016600 (15) [back to overview] | CR With Incomplete Blood Counts Rate |
| NCT01016600 (15) [back to overview] | Cytogenetic CR (CRc) Rate |
| NCT01016600 (15) [back to overview] | Duration of CR for Complete Responders |
| NCT01016600 (15) [back to overview] | Event Free Survival |
| NCT01016600 (15) [back to overview] | Morphologic Complete Remission Rate (CRm) |
| NCT01021423 (1) [back to overview] | Participants With Treatment Emergent Adverse Events (TEAEs) |
| NCT01029054 (3) [back to overview] | The Maximum Tolerated Dose (MTD) of Carfilzomib |
| NCT01029054 (3) [back to overview] | The Percentage of Patients Alive Without Progression |
| NCT01029054 (3) [back to overview] | The Percentage of Patients That Achieve a Response to Treatment |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 |
| NCT01029262 (29) [back to overview] | Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24 |
| NCT01029262 (29) [back to overview] | Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48 |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24 |
| NCT01029262 (29) [back to overview] | Time to 56-Day RBC-Transfusion-Independent (TI) Response as Determined by the Sponsor |
| NCT01029262 (29) [back to overview] | Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC) |
| NCT01029262 (29) [back to overview] | Percentage of Participants Who Achieved RBC Transfusion Independence With a Duration of ≥ 24 Weeks (168 Days) as Determined by the Sponsor |
| NCT01029262 (29) [back to overview] | Kaplan Meier Estimates of Duration of 56-day RBC Transfusion Independence Response as Determined by the Sponsor |
| NCT01029262 (29) [back to overview] | Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML) |
| NCT01029262 (29) [back to overview] | Kaplan Meier Estimate for Overall Survival (OS) |
| NCT01029262 (29) [back to overview] | Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Related to Adverse Events Per Person Year |
| NCT01029262 (29) [back to overview] | Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years |
| NCT01032291 (3) [back to overview] | Best Overall Response Assessed by an Independent Review Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) During the Proof of Concept Period Prior to Early Study Termination |
| NCT01032291 (3) [back to overview] | Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period |
| NCT01032291 (3) [back to overview] | Participants With Treatment-Emergent Adverse Events (TEAE) |
| NCT01034592 (7) [back to overview] | Duration of Response |
| NCT01034592 (7) [back to overview] | Hemoglobin Concentration |
| NCT01034592 (7) [back to overview] | Red Blood Cell (RBC) Transfusion Independence |
| NCT01034592 (7) [back to overview] | Platelet Response |
| NCT01034592 (7) [back to overview] | Toxicity |
| NCT01034592 (7) [back to overview] | Red Blood Cell (RBC) Transfusions |
| NCT01034592 (7) [back to overview] | Neutrophil Response |
| NCT01035463 (3) [back to overview] | Overall Survival |
| NCT01035463 (3) [back to overview] | Maximum Tolerated Dose of Lenalidomide (Phase I) |
| NCT01035463 (3) [back to overview] | Event-free Survival |
| NCT01038635 (3) [back to overview] | Overall Response: Number of Participants With CR or CRi Response |
| NCT01038635 (3) [back to overview] | Overall Response Rate (ORR) of Lenalidomide in Combination With 5-azacytidine (5-AZA) in Participants With Leukemia |
| NCT01038635 (3) [back to overview] | Number of Dose Limiting Toxicities for Determining Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With 5-azacytidine (5-AZA) |
| NCT01049945 (6) [back to overview] | Progression Free Survival (Phase II) |
| NCT01049945 (6) [back to overview] | Overall Survival (Phase II) |
| NCT01049945 (6) [back to overview] | Event Free Survival (Phase II) |
| NCT01049945 (6) [back to overview] | Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I) |
| NCT01049945 (6) [back to overview] | Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR). |
| NCT01049945 (6) [back to overview] | Duration of Response (DOR) (Phase II) |
| NCT01050790 (6) [back to overview] | Complete Response Rate at 6 Months |
| NCT01050790 (6) [back to overview] | Time to Progression Post Transplant |
| NCT01050790 (6) [back to overview] | CTA Expression Before and After Azacitidine Therapy |
| NCT01050790 (6) [back to overview] | Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment |
| NCT01050790 (6) [back to overview] | Progression-free and Overall Survival |
| NCT01050790 (6) [back to overview] | Toxicity as Assessed by NCI CTCAE v3.0 |
| NCT01054144 (5) [back to overview] | Combined Therapy - Median Progression Free Survival |
| NCT01054144 (5) [back to overview] | Number of Participants With 1 Year Overall Survival (OS) |
| NCT01054144 (5) [back to overview] | Number of Participants With Serious Adverse Events |
| NCT01054144 (5) [back to overview] | Single Agent - Median Progressive Free Survival (PFS) |
| NCT01054144 (5) [back to overview] | Response Rate |
| NCT01057121 (4) [back to overview] | Tumor Response Rate |
| NCT01057121 (4) [back to overview] | Maximum Tolerated Dose of Lenalidomide Defined as the Dose Level at Which 0/6 or 1/6 Subjects Experience Dose Limiting Toxicity (DLT) With the Next Higher Dose Having at Least 2/3 or 2/6 Subjects Encountering DLT (Phase I) |
| NCT01057121 (4) [back to overview] | Time to Death |
| NCT01057121 (4) [back to overview] | Time to Response |
| NCT01060384 (2) [back to overview] | Phase I: Maximum Tolerated Dose (MTD) of Lenalidomide |
| NCT01060384 (2) [back to overview] | Phase I and Phase II: Event Free Survival and Overall Survival |
| NCT01075321 (5) [back to overview] | Overall Survival for All Eligible Patients |
| NCT01075321 (5) [back to overview] | Progression-Free Survival For All Eligible Patients |
| NCT01075321 (5) [back to overview] | Time to Treatment Failure for All Eligible Patients |
| NCT01075321 (5) [back to overview] | Number of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I) |
| NCT01075321 (5) [back to overview] | Duration of Response for All Eligible Patients |
| NCT01076543 (5) [back to overview] | Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only |
| NCT01076543 (5) [back to overview] | Complete Response (Phase II) |
| NCT01076543 (5) [back to overview] | Overall Response Rate (Phase II) |
| NCT01076543 (5) [back to overview] | Overall Survival (OS) (Phase II) |
| NCT01076543 (5) [back to overview] | Progression-free Survival (PFS) (Phase II) |
| NCT01079936 (4) [back to overview] | Participants With Grade 3 =/> Adverse Events |
| NCT01079936 (4) [back to overview] | Number of Participants With Response (CR at Day 90) |
| NCT01079936 (4) [back to overview] | Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II) |
| NCT01079936 (4) [back to overview] | Maximum Tolerated Dose (MTD) of Lenalidomide |
| NCT01080391 (7) [back to overview] | Overall Response Rate |
| NCT01080391 (7) [back to overview] | Duration of Response |
| NCT01080391 (7) [back to overview] | Duration of Disease Control |
| NCT01080391 (7) [back to overview] | Disease Control Rate |
| NCT01080391 (7) [back to overview] | Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores |
| NCT01080391 (7) [back to overview] | Progression-free Survival (PFS) |
| NCT01080391 (7) [back to overview] | Overall Survival |
| NCT01088048 (15) [back to overview] | Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) |
| NCT01088048 (15) [back to overview] | Plasma Concentration of IDELA (Cohort 7) |
| NCT01088048 (15) [back to overview] | Plasma Concentration of IDELA (Cohort 6) |
| NCT01088048 (15) [back to overview] | Time to Response |
| NCT01088048 (15) [back to overview] | Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) |
| NCT01088048 (15) [back to overview] | Progression-free Survival |
| NCT01088048 (15) [back to overview] | Overall Survival |
| NCT01088048 (15) [back to overview] | Overall Response Rate |
| NCT01088048 (15) [back to overview] | Duration of Response |
| NCT01088048 (15) [back to overview] | Plasma Concentration of Bendamustine |
| NCT01088048 (15) [back to overview] | Plasma Concentration of IDELA (Cohort 4) |
| NCT01088048 (15) [back to overview] | Duration of Exposure to IDELA |
| NCT01088048 (15) [back to overview] | Plasma Concentration of Lenalidomide |
| NCT01088048 (15) [back to overview] | Plasma Concentration of Everolimus |
| NCT01088048 (15) [back to overview] | Toxicity of Administration of IDELA |
| NCT01093183 (4) [back to overview] | Proportion of Patients Achieving CR |
| NCT01093183 (4) [back to overview] | Overall Survival |
| NCT01093183 (4) [back to overview] | Number of Patients Achieving Objective PSA Response (50% Decrease in PSA Levels Sustained for at Least 4 Weeks) as Defined by PSA Working Group Criteria |
| NCT01093183 (4) [back to overview] | Maximum Tolerated Dose of Lenalidomide Administered in Combination With Oral Cyclophosphamide (Phase I) |
| NCT01109004 (10) [back to overview] | Percentage of Participants With Overall Survival (OS) |
| NCT01109004 (10) [back to overview] | Percentage of Participants With Disease Progression |
| NCT01109004 (10) [back to overview] | MOS SF-36 Physical Component Summary |
| NCT01109004 (10) [back to overview] | Percentage of Participants With Treatment-related Mortality (TRM) |
| NCT01109004 (10) [back to overview] | Number of Participants With Treatment Response |
| NCT01109004 (10) [back to overview] | FACT-G Total Score |
| NCT01109004 (10) [back to overview] | MOS SF-36 Mental Component Summary |
| NCT01109004 (10) [back to overview] | FACT-BMT Score |
| NCT01109004 (10) [back to overview] | Percentage of Participants With Progression-free Survival (PFS) |
| NCT01109004 (10) [back to overview] | FACT-BMT Trial Outcome Index |
| NCT01121757 (4) [back to overview] | Overall Response |
| NCT01121757 (4) [back to overview] | Response Predicted by Molecular Signatures Compared to True Response |
| NCT01121757 (4) [back to overview] | Number of Participants With Grade 3 and 4 Toxicities |
| NCT01121757 (4) [back to overview] | Overall Response |
| NCT01123356 (4) [back to overview] | Frequency of Adverse and Severe Adverse Events |
| NCT01123356 (4) [back to overview] | Dose Reductions Due to Adverse Events. |
| NCT01123356 (4) [back to overview] | Frequency of Adverse Events |
| NCT01123356 (4) [back to overview] | Overall Response Rate |
| NCT01125176 (5) [back to overview] | Time to Response |
| NCT01125176 (5) [back to overview] | Overall Survival |
| NCT01125176 (5) [back to overview] | Progression Free Survival |
| NCT01125176 (5) [back to overview] | Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response |
| NCT01125176 (5) [back to overview] | Duration of Response |
| NCT01133275 (2) [back to overview] | Number of Participants With Erythroid Response |
| NCT01133275 (2) [back to overview] | Number of Participants With Grade 3 or 4 Adverse Events Possibly Related to Treatment |
| NCT01133665 (38) [back to overview] | Number of Participants With Headache Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hyperglycemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hypoalbuminemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hypocalcaemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hypokalemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Diarrhea Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hypophosphatemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Aspartate Aminotransferase Increased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Anorexia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Anemia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Alkaline Phosphatase Increased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Alanine Aminotransferase Increased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Acneiform Rash Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Correlate the Presence of Specific Fc RIIIa Polymorphisms With Progression-free Survival in Subjects Receiving Cetuximab and Lenalidomide for SCCHN. |
| NCT01133665 (38) [back to overview] | Number of Participants With Back Pain Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Weight Loss Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Vomiting Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Thrombocytopenia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Pain Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Oral Mucositis Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Neutropenia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Neck Pain Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Blood Bilirubin Increased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With White Blood Cell Decreased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Xerostomia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With C. Diff Infection Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Constipation Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Hyponatremia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Infusion Related Reaction Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Lymphocyte Count Increased Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Lymphopenia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Maculopapular Rash Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Nausea Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Dyspnea Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Fatigue Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Febrile Neutropenia Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Fever Related to Cetuximab/Lenalidomide |
| NCT01133665 (38) [back to overview] | Number of Participants With Peripheral Sensory Neuropathy Related to Cetuximab/Lenalidomide |
| NCT01142232 (3) [back to overview] | Phase I: Number of Patients With Dose Limiting Toxicity |
| NCT01142232 (3) [back to overview] | Phase II: Overall Response Rate |
| NCT01142232 (3) [back to overview] | Phase II: Treatment-Related Adverse Events Grade 3 or Higher |
| NCT01145495 (3) [back to overview] | Number of Participants Who Achieved a Complete Response |
| NCT01145495 (3) [back to overview] | Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
| NCT01145495 (3) [back to overview] | Disease Progression |
| NCT01155583 (5) [back to overview] | Percent of Participants With Clinical Benefit and Response According to International Response Criteria |
| NCT01155583 (5) [back to overview] | Percent of Participants With Clinical Benefit and Response According to International Response Criteria |
| NCT01155583 (5) [back to overview] | Phase I: Highest Tolerated Low Dose (HTLD) |
| NCT01155583 (5) [back to overview] | Overall Survival |
| NCT01155583 (5) [back to overview] | Median Progression-free Survival (PFS) |
| NCT01160484 (7) [back to overview] | Follow-up Time |
| NCT01160484 (7) [back to overview] | Progression-free Survival |
| NCT01160484 (7) [back to overview] | Duration of Response |
| NCT01160484 (7) [back to overview] | Time to Best Response |
| NCT01160484 (7) [back to overview] | Time to First Response |
| NCT01160484 (7) [back to overview] | Time to Progression |
| NCT01160484 (7) [back to overview] | International Myeloma Working Group (IMWG) Response Criteria |
| NCT01169337 (7) [back to overview] | Proportion of Participants With Response (Phase III Secondary Endpoint) |
| NCT01169337 (7) [back to overview] | Proportion of Patients With Grade 3 Adverse Events That Effect Vital Organ Function or Any Grade 4 or Higher Non-hematologic Adverse Events (Phase II Primary Endpoint) |
| NCT01169337 (7) [back to overview] | 1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint) |
| NCT01169337 (7) [back to overview] | 2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint) |
| NCT01169337 (7) [back to overview] | 2-year Progression-free Rate (Phase III Secondary Endpoint) |
| NCT01169337 (7) [back to overview] | 2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint) |
| NCT01169337 (7) [back to overview] | Proportion of Participants With Response (Phase II Secondary Endpoint) |
| NCT01197560 (9) [back to overview] | Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment |
| NCT01197560 (9) [back to overview] | Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC) |
| NCT01197560 (9) [back to overview] | Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
| NCT01197560 (9) [back to overview] | Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase |
| NCT01199575 (2) [back to overview] | Overall Response Rate (ORR) |
| NCT01199575 (2) [back to overview] | Adverse Events to Study Treatment |
| NCT01208051 (6) [back to overview] | Overall Survival (Final Results After Crossover) |
| NCT01208051 (6) [back to overview] | Percent Change in Tumor Size (Phase II) |
| NCT01208051 (6) [back to overview] | Progression-free Survival (Final Results After Crossover) |
| NCT01208051 (6) [back to overview] | Progression-free Survival (Phase II Futility Analysis) |
| NCT01208051 (6) [back to overview] | Dose Limiting Toxicity |
| NCT01208051 (6) [back to overview] | Objective Response Rate |
| NCT01208662 (17) [back to overview] | 5-Year Overall Survival (OS) |
| NCT01208662 (17) [back to overview] | Partial Response (PR) Rate |
| NCT01208662 (17) [back to overview] | 5-Year Time to Progression (TTP) |
| NCT01208662 (17) [back to overview] | Change From Baseline on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) |
| NCT01208662 (17) [back to overview] | Median Maintenance Treatment Duration |
| NCT01208662 (17) [back to overview] | Median Event Free Survival (EFS) |
| NCT01208662 (17) [back to overview] | Quality-Adjusted Life Years (QALYs) |
| NCT01208662 (17) [back to overview] | 5-year Cumulative Incidence of Second Primary Malignancy (SPM) |
| NCT01208662 (17) [back to overview] | Median Progression-Free Survival (PFS) |
| NCT01208662 (17) [back to overview] | Subsequent Therapy Rate |
| NCT01208662 (17) [back to overview] | Very Good Partial Response (VGPR) Rate |
| NCT01208662 (17) [back to overview] | Change From Baseline on the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30): Global Health Status/Quality of Life (QoL) Sub-scale |
| NCT01208662 (17) [back to overview] | Median Treatment Duration |
| NCT01208662 (17) [back to overview] | Next Generation Sequencing (NGS) Minimal Residual Disease Negative (MRD-) Rate at Maintenance Start |
| NCT01208662 (17) [back to overview] | Median Duration of Response: Partial Response (DOR PR) |
| NCT01208662 (17) [back to overview] | Grade 3 or Higher Treatment-Related Non-Hematologic Adverse Event (AE) Rate |
| NCT01208662 (17) [back to overview] | Complete Response (CR) Rate |
| NCT01215344 (2) [back to overview] | The Percent of Patients With Minimal Residual Disease (MRD) Status Changing to Negative at Day 100 (Post-AHCT), Among Patients With MRD Positive at the End of Induction (EOI). |
| NCT01215344 (2) [back to overview] | Progression Free Survival by MRD Status at Day 100. |
| NCT01216683 (25) [back to overview] | 3-year Progression-free Survival Rate |
| NCT01216683 (25) [back to overview] | 1-year Post-induction Disease-free Survival (DFS) Rate |
| NCT01216683 (25) [back to overview] | 1-year Disease-free Survival (DFS) Rate |
| NCT01216683 (25) [back to overview] | 1-year Disease-free Survival (DFS) Rate |
| NCT01216683 (25) [back to overview] | Complete Remission (CR) Rate |
| NCT01216683 (25) [back to overview] | Complete Remission (CR) Rate |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Baseline |
| NCT01216683 (25) [back to overview] | Complete Remission (CR) Rate |
| NCT01216683 (25) [back to overview] | Proportion of Patients With Grade 3 or Higher Peripheral Neuropathy |
| NCT01216683 (25) [back to overview] | 5-year Overall Survival Rate |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at the End of Induction Treatment |
| NCT01216683 (25) [back to overview] | Progression-free Survival |
| NCT01216683 (25) [back to overview] | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Mid-induction Treatment |
| NCT01216683 (25) [back to overview] | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at End of Induction Treatment |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at End of Induction Treatment |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Baseline |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at End of Induction Treatment |
| NCT01216683 (25) [back to overview] | Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Baseline |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Mid-induction Treatment |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Baseline |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Mid-induction Treatment |
| NCT01216683 (25) [back to overview] | 5-year Overall Survival Rate |
| NCT01216683 (25) [back to overview] | 5-year Overall Survival Rate |
| NCT01216683 (25) [back to overview] | Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Mid-treatment |
| NCT01216683 (25) [back to overview] | 3-year Progression-free Survival Rate |
| NCT01217957 (18) [back to overview] | Phase 2: 1 Year Survival Rate |
| NCT01217957 (18) [back to overview] | Phase 2: Duration of Response (DOR) |
| NCT01217957 (18) [back to overview] | Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone |
| NCT01217957 (18) [back to overview] | Phase 2: Overall Response Rate (ORR) |
| NCT01217957 (18) [back to overview] | Phase 2: Overall Survival (OS) |
| NCT01217957 (18) [back to overview] | Phase 2: Progression Free Survival (PFS) |
| NCT01217957 (18) [back to overview] | Phase 2: Time to Best Response |
| NCT01217957 (18) [back to overview] | Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone |
| NCT01217957 (18) [back to overview] | Phase 1: Rac: Accumulation Ratio of Ixazomib |
| NCT01217957 (18) [back to overview] | Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib |
| NCT01217957 (18) [back to overview] | Phase 2: Time to Progression (TTP) |
| NCT01217957 (18) [back to overview] | Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib |
| NCT01217957 (18) [back to overview] | Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib |
| NCT01217957 (18) [back to overview] | Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability |
| NCT01217957 (18) [back to overview] | Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) |
| NCT01217957 (18) [back to overview] | Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR) |
| NCT01217957 (18) [back to overview] | Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation |
| NCT01217957 (18) [back to overview] | Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone |
| NCT01222195 (1) [back to overview] | Number of Patients With a Transfusion Independence Response |
| NCT01239797 (6) [back to overview] | Median Progression Free Survival (PFS) |
| NCT01239797 (6) [back to overview] | Objective Response Rate (ORR) |
| NCT01239797 (6) [back to overview] | Median Progression Free Survival (PFS) - Extended Collection |
| NCT01239797 (6) [back to overview] | Median Overall Survival (OS) |
| NCT01239797 (6) [back to overview] | Change From Baseline of Mean Score Pain Severity (BPI-SF) |
| NCT01239797 (6) [back to overview] | Change From Baseline of Mean Score Pain Interference (BPI-SF) |
| NCT01241734 (7) [back to overview] | Stage II - Overall Response Rate |
| NCT01241734 (7) [back to overview] | Stage I - Dose Limiting Toxicity Incidence Rate |
| NCT01241734 (7) [back to overview] | Stage I - Safety (Type, Frequency, Severity and Relationship of Adverse Events to Study Treatment) and Tolerability |
| NCT01241734 (7) [back to overview] | Stage II - 1 Year Overall Survival (OS) |
| NCT01241734 (7) [back to overview] | Stage II - 1 Year Progression Free Survival (PFS) |
| NCT01241734 (7) [back to overview] | Stage II - 2 Year Overall Survival (OS) |
| NCT01241734 (7) [back to overview] | Stage II - 2 Year Progression Free Survival (PFS) |
| NCT01241786 (4) [back to overview] | The Overall Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine |
| NCT01241786 (4) [back to overview] | Assess for Treatment Related Toxicity Following Administration of Lenalidomide/ Azacitidine. |
| NCT01241786 (4) [back to overview] | the Rate of Response to the Combination of Azacitidine + Lenalidomide in Select Patients |
| NCT01241786 (4) [back to overview] | The Progression Free Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine |
| NCT01243944 (13) [back to overview] | Duration of Reduction in Spleen Volume |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32 |
| NCT01243944 (13) [back to overview] | Estimated Duration of the Primary Response |
| NCT01243944 (13) [back to overview] | Duration of the Absence of Phlebotomy Eligibility |
| NCT01243944 (13) [back to overview] | Estimated Duration of the Complete Hematological Remission |
| NCT01243944 (13) [back to overview] | Duration of The Overall Clinicohematologic Response |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Achieving Complete Hematological Remission at Week 32 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Achieving a Primary Response at Week 32 |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Achieving a Durable Primary Response at Week 48 |
| NCT01246076 (5) [back to overview] | Time to Discontinuation of Treatment |
| NCT01246076 (5) [back to overview] | Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria |
| NCT01246076 (5) [back to overview] | Toxicity as Measured by Number of Participants Who Experienced Related Grade 3-5 Adverse Events Based on CTCAE Version 4 |
| NCT01246076 (5) [back to overview] | Duration of Response |
| NCT01246076 (5) [back to overview] | Overall Survival Rate |
| NCT01303965 (8) [back to overview] | Phase I: Number of Participants With Dose Limiting Toxicity |
| NCT01303965 (8) [back to overview] | Phase II - Time to Platelet Engraftment |
| NCT01303965 (8) [back to overview] | Phase II - Time to Neutrophil Engraftment |
| NCT01303965 (8) [back to overview] | Phase II - Percent of Patients With Treatment-related Deaths at 100 Days |
| NCT01303965 (8) [back to overview] | Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD) |
| NCT01303965 (8) [back to overview] | Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD) |
| NCT01303965 (8) [back to overview] | Phase II - Percent of Patients With Treatment-related Deaths at 1 Year |
| NCT01303965 (8) [back to overview] | Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant |
| NCT01335399 (5) [back to overview] | Progression Free Survival (PFS) Rate at Specific Time-points |
| NCT01335399 (5) [back to overview] | Mean Change From Baseline of Pain Severity Score and Pain Interference Score |
| NCT01335399 (5) [back to overview] | Progression-Free Survival (PFS) |
| NCT01335399 (5) [back to overview] | Overall Survival (OS) |
| NCT01335399 (5) [back to overview] | Objective Response Rate (ORR) |
| NCT01342172 (4) [back to overview] | Maximum Tolerated Dose (MTD) of Lenalidomide |
| NCT01342172 (4) [back to overview] | Best Overall Response |
| NCT01342172 (4) [back to overview] | Number of Grade >=3 Adverse Events |
| NCT01342172 (4) [back to overview] | The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide |
| NCT01348919 (8) [back to overview] | Maximum Tolerated Dose of CEP-18770 |
| NCT01348919 (8) [back to overview] | Duration of Response (DOR) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria |
| NCT01348919 (8) [back to overview] | Overall Response Rate (ORR) in Participants Treated at the (Maximum Tolerated Dose) MTD, as Assessed Using International Myeloma Working Group (IMWG) Criteria |
| NCT01348919 (8) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT01348919 (8) [back to overview] | Time to Reach Cmax (Tmax) of CEP-18770 |
| NCT01348919 (8) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of CEP-18770 |
| NCT01348919 (8) [back to overview] | Area Under the Plasma Concentration-Time Curve From Time 0 to t (AUC0-t) of CEP-18770 |
| NCT01348919 (8) [back to overview] | Time to Progression (TTP) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria |
| NCT01349569 (4) [back to overview] | Grade 3-4 Toxicity |
| NCT01349569 (4) [back to overview] | Response Conversion Rate |
| NCT01349569 (4) [back to overview] | Time to Response |
| NCT01349569 (4) [back to overview] | Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells |
| NCT01355705 (4) [back to overview] | Time-to-next Treatment |
| NCT01355705 (4) [back to overview] | Response Rates After Amrubicin + Lenalidomide + Dexamethasone, Per International Myeloma Working Group Uniform Response Criteria |
| NCT01355705 (4) [back to overview] | Duration of Response (DOR) |
| NCT01355705 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT01358734 (6) [back to overview] | Percentage of Participants Alive at One Year |
| NCT01358734 (6) [back to overview] | Kaplan Meier Estimates for One Year Survival |
| NCT01358734 (6) [back to overview] | Percentage of Participants With 30-Day Treatment-Related Mortality |
| NCT01358734 (6) [back to overview] | Number of Participants With a Second Primary Malignancy |
| NCT01358734 (6) [back to overview] | Overall Survival |
| NCT01358734 (6) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT01373229 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT01373229 (4) [back to overview] | Overall Survival (OS) |
| NCT01373229 (4) [back to overview] | Overall Response (Complete Response/Partial Response) |
| NCT01373229 (4) [back to overview] | Maximum Tolerated Dose |
| NCT01373294 (2) [back to overview] | Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
| NCT01373294 (2) [back to overview] | Arm A: Progression Free Survival (PFS) |
| NCT01374217 (4) [back to overview] | Duration of Response |
| NCT01374217 (4) [back to overview] | Quality of Life Scores |
| NCT01374217 (4) [back to overview] | Time to Progression |
| NCT01374217 (4) [back to overview] | Response Rate |
| NCT01375140 (1) [back to overview] | Participants With Objective Response |
| NCT01380106 (2) [back to overview] | Serious Adverse Events |
| NCT01380106 (2) [back to overview] | Duration Until Best Response (at Least MR or Minimal Response) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Very Good Partial Response (VGPR) |
| NCT01383928 (29) [back to overview] | Phase 2: Time to Response |
| NCT01383928 (29) [back to overview] | Progression Free Survival (PFS) |
| NCT01383928 (29) [back to overview] | Time to Disease Progression (TTP) |
| NCT01383928 (29) [back to overview] | Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib |
| NCT01383928 (29) [back to overview] | Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
| NCT01383928 (29) [back to overview] | Phase 1: Number of Participants With Markedly Abnormal Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) |
| NCT01383928 (29) [back to overview] | Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Related to Neurotoxicity |
| NCT01383928 (29) [back to overview] | Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) |
| NCT01383928 (29) [back to overview] | Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16 |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Stringent Complete Response (sCR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Minimal Response (MR) |
| NCT01383928 (29) [back to overview] | Phase 1: Recommended Phase 2 Dose (RP2D) |
| NCT01383928 (29) [back to overview] | Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Year 1 |
| NCT01383928 (29) [back to overview] | Overall Survival |
| NCT01383928 (29) [back to overview] | Phase 1: Maximum Tolerated Dose (MTD) |
| NCT01383928 (29) [back to overview] | Phase 1: Percentage of Participants With Best Overall Response |
| NCT01383928 (29) [back to overview] | Phase 1: Rac: Accumulation Ratio of Ixazomib |
| NCT01383928 (29) [back to overview] | Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib |
| NCT01383928 (29) [back to overview] | Phase 2: Duration of Response (DOR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants Experiencing Serious Adverse Events |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Complete Response (CR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Near Complete Response (nCR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Overall Response (CR+VGPR+PR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Partial Response (PR) |
| NCT01383928 (29) [back to overview] | Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation |
| NCT01393964 (11) [back to overview] | Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests |
| NCT01393964 (11) [back to overview] | Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests |
| NCT01393964 (11) [back to overview] | Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests |
| NCT01393964 (11) [back to overview] | Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method |
| NCT01393964 (11) [back to overview] | Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method |
| NCT01393964 (11) [back to overview] | Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method |
| NCT01393964 (11) [back to overview] | Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method |
| NCT01393964 (11) [back to overview] | Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method |
| NCT01393964 (11) [back to overview] | Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method |
| NCT01393964 (11) [back to overview] | Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose. |
| NCT01393964 (11) [back to overview] | Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died |
| NCT01401322 (1) [back to overview] | Time-to-Progression (TTP) |
| NCT01402284 (7) [back to overview] | Rate of Minimal Residual Disease (MRD) by Flow Cytometry |
| NCT01402284 (7) [back to overview] | Percentage of Responders With Duration of Response (DOR) at 48 Months |
| NCT01402284 (7) [back to overview] | Overall Survival (OS) Rate |
| NCT01402284 (7) [back to overview] | Overall Response Rate |
| NCT01402284 (7) [back to overview] | Complete Response (CR) and Minimal Residual Disease Neg (MRDneg) CR Rates at Treatment Intervals With Carfilzomib, Lenalidomide & Dexamethasone (CRd) in New Multiple Myeloma Patients After 8 Cycles of Induction, 1 Year Maintenance, and 2 Years Maintenance |
| NCT01402284 (7) [back to overview] | Number of Participants With Serious and Non-serious Adverse Events |
| NCT01402284 (7) [back to overview] | Progression Free Survival (PFS) at 48 Months |
| NCT01403246 (1) [back to overview] | Number of Dose Limiting Toxic Events (DLT) of Lenalidomide Given in Combination With Chlorambucil. |
| NCT01419795 (6) [back to overview] | Incidences of Grades II-IV Acute GVHD and Limited or Extensive Chronic GVHD |
| NCT01419795 (6) [back to overview] | Improvement in Overall Survival of Patients Receiving Lenalidomide With or Without Rituximab in Comparison to Historical Controls Managed by Single or Multiple Chemotherapeutic Agents or Donor Lymphocyte Infusion (DLI) (Cohort 1) |
| NCT01419795 (6) [back to overview] | Rate of Response (CR, PR, or SD) and Time to Progression |
| NCT01419795 (6) [back to overview] | Grade III-IV Toxicity in Patients Receiving Lenalidomide With or Without Rituximab |
| NCT01419795 (6) [back to overview] | Comparison of Rates of Overall Response and Complete Remission Between the First, Second, and Third Cohorts |
| NCT01419795 (6) [back to overview] | Comparison of Incidences of Adverse Events Between the First, Second, and Third Cohorts |
| NCT01421186 (8) [back to overview] | Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202 |
| NCT01421186 (8) [back to overview] | Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202 |
| NCT01421186 (8) [back to overview] | Progression-free Survival |
| NCT01421186 (8) [back to overview] | Time to Progression |
| NCT01421186 (8) [back to overview] | Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087 |
| NCT01421186 (8) [back to overview] | Duration of Response |
| NCT01421186 (8) [back to overview] | Number of Participants Who Develop Anti-MOR03087 Antibodies |
| NCT01421186 (8) [back to overview] | Overall Response Rate |
| NCT01442714 (3) [back to overview] | Median Duration of Response |
| NCT01442714 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT01442714 (3) [back to overview] | Overall Survival |
| NCT01460940 (3) [back to overview] | Progression-free Survival in Patients With Previously Treated Hodgkin's Lymphoma Receiving Combined Lenalidomide and Panobinostat |
| NCT01460940 (3) [back to overview] | Determine the Overall Response Rate (ORR), Including Complete Responses (CR) and Partial Responses (PR) |
| NCT01460940 (3) [back to overview] | Assess the Safety and Tolerability of Combined Lenalidomide and Panobinostat in Patients With Previously Treated Hodgkin's Lymphoma. |
| NCT01463670 (2) [back to overview] | Number of Participants Evaluated for Toxicity |
| NCT01463670 (2) [back to overview] | Overall Response Rate (ORR) |
| NCT01472562 (1) [back to overview] | Overall Response Rate |
| NCT01496976 (4) [back to overview] | Number of Participants With Complete Response (CR) |
| NCT01496976 (4) [back to overview] | Number of Participants With Overall Survival (OS) |
| NCT01496976 (4) [back to overview] | Number of Participants With Partial Response (PR) |
| NCT01496976 (4) [back to overview] | Rate of Progression/Relapse Free Survival (PFS) |
| NCT01497496 (1) [back to overview] | Objective Response Rate (ORR) |
| NCT01522976 (5) [back to overview] | Overall Survival |
| NCT01522976 (5) [back to overview] | Relapse-free Survival |
| NCT01522976 (5) [back to overview] | Response Rate (Phase II) |
| NCT01522976 (5) [back to overview] | Pre-study Cytogenetic Abnormalities |
| NCT01522976 (5) [back to overview] | Toxicity Rate |
| NCT01531998 (2) [back to overview] | Number of Participants With Response |
| NCT01531998 (2) [back to overview] | Maximum Tolerated Dose (MTD) of Siltuximab |
| NCT01553149 (6) [back to overview] | Pharmacokinetic Parameters of Lenalidomide |
| NCT01553149 (6) [back to overview] | Overall Survival [OS] |
| NCT01553149 (6) [back to overview] | Event-free Survival [EFS] |
| NCT01553149 (6) [back to overview] | Number of Patients Who Demonstrate Complete or Partial Response |
| NCT01553149 (6) [back to overview] | Number of Patients Who Demonstrate Early Progression |
| NCT01553149 (6) [back to overview] | Number of Patients With Toxic Events After 2 Dose Reductions |
| NCT01559935 (4) [back to overview] | Stem Cells Collection |
| NCT01559935 (4) [back to overview] | Response to Car-BiRD Treatment. |
| NCT01559935 (4) [back to overview] | Event Free Survival |
| NCT01559935 (4) [back to overview] | Progression Free Survival |
| NCT01564537 (18) [back to overview] | Duration of Response (DOR) |
| NCT01564537 (18) [back to overview] | Overall Response Rate (ORR) as Assessed by the IRC |
| NCT01564537 (18) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20) |
| NCT01564537 (18) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30) |
| NCT01564537 (18) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30) |
| NCT01564537 (18) [back to overview] | Time to Progression (TTP) as Assessed by the IRC |
| NCT01564537 (18) [back to overview] | PFS in High-Risk Participants |
| NCT01564537 (18) [back to overview] | Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC |
| NCT01564537 (18) [back to overview] | Overall Response Rate in Participants Defined by Polymorphism |
| NCT01564537 (18) [back to overview] | Overall Survival (OS) |
| NCT01564537 (18) [back to overview] | Plasma Concentration Over Time for Ixazomib |
| NCT01564537 (18) [back to overview] | Plasma Concentration Over Time for Ixazomib |
| NCT01564537 (18) [back to overview] | Number of Participants With Change From Baseline in Pain Response |
| NCT01564537 (18) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01564537 (18) [back to overview] | Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)] |
| NCT01564537 (18) [back to overview] | Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC) |
| NCT01564537 (18) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20) |
| NCT01564537 (18) [back to overview] | OS in High-Risk Participants |
| NCT01572480 (6) [back to overview] | Percentage of Participants With Minimal Residual Disease (MRD)Negative Complete Response (CR) Per International Myeloma Working Group (IMWG) Criteria |
| NCT01572480 (6) [back to overview] | Overall Response Rate |
| NCT01572480 (6) [back to overview] | Percentage of Participants That Have Minimal Residual Disease (MRD)-Negative Complete Response (CR) for a Minimum of 1 Year |
| NCT01572480 (6) [back to overview] | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
| NCT01572480 (6) [back to overview] | Clinical Progression Free Survival |
| NCT01572480 (6) [back to overview] | Biochemical Progression Free Survival |
| NCT01575860 (2) [back to overview] | Progression Free Survival |
| NCT01575860 (2) [back to overview] | Number of Subjects With Dose-limiting Toxicities |
| NCT01600053 (1) [back to overview] | Recording of the Occurrence of Adverse Events |
| NCT01615029 (8) [back to overview] | Phase 2: Time to Progression (TTP) |
| NCT01615029 (8) [back to overview] | Phase 2: Duration of Response |
| NCT01615029 (8) [back to overview] | Phase 1: Percentage of Participants With Overall Response Rate (ORR) |
| NCT01615029 (8) [back to overview] | Phase 2: Overall Survival (OS) |
| NCT01615029 (8) [back to overview] | Phase 2: Percentage of Participants With Overall Response Rate (ORR) |
| NCT01615029 (8) [back to overview] | Phase 2: Progression-Free Survival (PFS) |
| NCT01615029 (8) [back to overview] | Phase 2: Time to Response |
| NCT01615029 (8) [back to overview] | Phase 1: Time to Response |
| NCT01621672 (1) [back to overview] | Progression Free Survival (PFS) |
| NCT01645930 (12) [back to overview] | Duration of Response (DOR) |
| NCT01645930 (12) [back to overview] | Cmax: Maximum Observed Plasma Concentration for Ixazomib |
| NCT01645930 (12) [back to overview] | Cmax: Maximum Observed Plasma Concentration for Ixazomib |
| NCT01645930 (12) [back to overview] | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib |
| NCT01645930 (12) [back to overview] | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib |
| NCT01645930 (12) [back to overview] | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
| NCT01645930 (12) [back to overview] | Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events |
| NCT01645930 (12) [back to overview] | Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity |
| NCT01645930 (12) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01645930 (12) [back to overview] | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
| NCT01645930 (12) [back to overview] | Percentage of Participants With Confirmed Best Response Category |
| NCT01645930 (12) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs) |
| NCT01649791 (3) [back to overview] | Incidence of Immune Mediated Flare Reaction |
| NCT01649791 (3) [back to overview] | Median Progression-free Survival |
| NCT01649791 (3) [back to overview] | Overall Response Rate (CR+PR) |
| NCT01651039 (8) [back to overview] | Clinical Benefit Rate |
| NCT01651039 (8) [back to overview] | The Best Overall Response Rate (ORR) |
| NCT01651039 (8) [back to overview] | Response Rates |
| NCT01651039 (8) [back to overview] | Response Rates for Len Refractory Patients |
| NCT01651039 (8) [back to overview] | Disease Control Rate for Lens Refractory Rate |
| NCT01651039 (8) [back to overview] | Clinical Benefit Rate for Len Refractory Patients |
| NCT01651039 (8) [back to overview] | Overall Response Rate for Len Refractory Patients |
| NCT01651039 (8) [back to overview] | Disease Control Rate |
| NCT01659658 (21) [back to overview] | Plasma Concentration of Ixazomib |
| NCT01659658 (21) [back to overview] | Time To Subsequent Anticancer Treatment |
| NCT01659658 (21) [back to overview] | Percentage of Participants With Overall Hematologic Response |
| NCT01659658 (21) [back to overview] | Percentage of Participants With Complete Hematologic Response |
| NCT01659658 (21) [back to overview] | Time To Treatment Failure (TTF) |
| NCT01659658 (21) [back to overview] | Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate |
| NCT01659658 (21) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up |
| NCT01659658 (21) [back to overview] | 2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate |
| NCT01659658 (21) [back to overview] | Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up |
| NCT01659658 (21) [back to overview] | Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up |
| NCT01659658 (21) [back to overview] | Duration of Hematologic Response |
| NCT01659658 (21) [back to overview] | EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score |
| NCT01659658 (21) [back to overview] | Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score |
| NCT01659658 (21) [back to overview] | Hematologic Disease Progression Free Survival |
| NCT01659658 (21) [back to overview] | Number of Hospitalizations |
| NCT01659658 (21) [back to overview] | Number of Participants With Serious Adverse Events (SAEs) |
| NCT01659658 (21) [back to overview] | Overall Survival |
| NCT01659658 (21) [back to overview] | Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response |
| NCT01659658 (21) [back to overview] | Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up |
| NCT01659658 (21) [back to overview] | Vital Organ Progression Free Survival |
| NCT01659658 (21) [back to overview] | Progression Free Survival (PFS) |
| NCT01668719 (5) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT01668719 (5) [back to overview] | Response (Partial Response [PR] or Better) Rate |
| NCT01668719 (5) [back to overview] | Progression-free Survival |
| NCT01668719 (5) [back to overview] | Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone |
| NCT01668719 (5) [back to overview] | Overall Survival |
| NCT01675141 (3) [back to overview] | Number of Participants With Serious and Non-serious Adverse Events |
| NCT01675141 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT01675141 (3) [back to overview] | Duration of Response |
| NCT01698801 (6) [back to overview] | Time to Response |
| NCT01698801 (6) [back to overview] | Overall Survival (OS) |
| NCT01698801 (6) [back to overview] | Duration of Response |
| NCT01698801 (6) [back to overview] | Overall Response Rate |
| NCT01698801 (6) [back to overview] | Number of Participants With Adverse Events |
| NCT01698801 (6) [back to overview] | Progression Free Survival (PFS) |
| NCT01704781 (7) [back to overview] | Part A and B: Safety and Tolerability |
| NCT01704781 (7) [back to overview] | Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time |
| NCT01704781 (7) [back to overview] | Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity |
| NCT01704781 (7) [back to overview] | Part B: Incidents of Delayed-type Hypersensitivity |
| NCT01704781 (7) [back to overview] | Part B: Evaluate the Effect on HIV Viral Load |
| NCT01704781 (7) [back to overview] | Part B: Change in CD8 Count |
| NCT01704781 (7) [back to overview] | Part B: Change in CD4 Count |
| NCT01706666 (3) [back to overview] | Survival Time |
| NCT01706666 (3) [back to overview] | Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months |
| NCT01706666 (3) [back to overview] | Progression-free Survival |
| NCT01723839 (2) [back to overview] | Overall Response Rate |
| NCT01723839 (2) [back to overview] | Complete Response |
| NCT01724177 (8) [back to overview] | Time to Response |
| NCT01724177 (8) [back to overview] | Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC |
| NCT01724177 (8) [back to overview] | Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC |
| NCT01724177 (8) [back to overview] | Kaplan-Meier Estimate for Overall Survival |
| NCT01724177 (8) [back to overview] | Number of Participants With Treatment Emergent Adverse Events |
| NCT01724177 (8) [back to overview] | Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC |
| NCT01724177 (8) [back to overview] | Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC) |
| NCT01724177 (8) [back to overview] | Kaplan-Meier Estimate of Time to Progression (TTP) |
| NCT01729338 (11) [back to overview] | QLQ-C30 Question 30 |
| NCT01729338 (11) [back to overview] | Overall Response Rate (ORR) During Induction Therapy |
| NCT01729338 (11) [back to overview] | Median Time to Response |
| NCT01729338 (11) [back to overview] | QLQ-C30 Question 29 |
| NCT01729338 (11) [back to overview] | Median Progression-free Survival |
| NCT01729338 (11) [back to overview] | Median Overall Survival |
| NCT01729338 (11) [back to overview] | Median Duration of Response |
| NCT01729338 (11) [back to overview] | Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool |
| NCT01729338 (11) [back to overview] | Severe Adverse Event Rate |
| NCT01729338 (11) [back to overview] | Maximum Depth of Response During Induction Therapy |
| NCT01729338 (11) [back to overview] | Maximum Depth of Response During Maintenance Therapy |
| NCT01731886 (5) [back to overview] | Overall Survival Rate (OS) |
| NCT01731886 (5) [back to overview] | Overall Survival Rate (OS) |
| NCT01731886 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT01731886 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT01731886 (5) [back to overview] | Complete Response Rate |
| NCT01743859 (7) [back to overview] | Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts |
| NCT01743859 (7) [back to overview] | Progression-free Survival |
| NCT01743859 (7) [back to overview] | Response or Remission Duration |
| NCT01743859 (7) [back to overview] | Toxicity and SAEs Related to Treatment |
| NCT01743859 (7) [back to overview] | Determine Biomarkers That Predict Response/Toxicity |
| NCT01743859 (7) [back to overview] | Overall Response Rate |
| NCT01743859 (7) [back to overview] | Overall Survival |
| NCT01754857 (2) [back to overview] | Time to Progression |
| NCT01754857 (2) [back to overview] | Count of Events Related to Toxicity |
| NCT01772420 (7) [back to overview] | Number of Patients With Hematologic Improvement in Platelet Counts (HI-P) |
| NCT01772420 (7) [back to overview] | Number of Patients With Clinically Significant Bleeding Events |
| NCT01772420 (7) [back to overview] | Number of Patients With Hematologic Improvement in Neutrophil Counts (HI-N) |
| NCT01772420 (7) [back to overview] | Number of Patients Demonstrating Overall Hematologic Improvement (HI) |
| NCT01772420 (7) [back to overview] | Duration of Hematologic Improvement (HI) |
| NCT01772420 (7) [back to overview] | Time to Attain Hematologic Improvement (HI) |
| NCT01772420 (7) [back to overview] | Number of Patients With Hematologic Improvement in Erythrocyte Counts (HI-E) |
| NCT01779167 (1) [back to overview] | Number of Patients Who Demonstrate a Response (Complete, Partial, Minor) to Treatment |
| NCT01782963 (6) [back to overview] | Mean Plasma Bortezomib Concentration Following Intravenous and and Subcutaneous Injection |
| NCT01782963 (6) [back to overview] | Median Overall Survival |
| NCT01782963 (6) [back to overview] | Median Progression Free Survival |
| NCT01782963 (6) [back to overview] | Median Time to Response |
| NCT01782963 (6) [back to overview] | Number of Participants With Grade 3 or Higher Treatment Related Adverse Events |
| NCT01782963 (6) [back to overview] | Objective Response Rate |
| NCT01794039 (4) [back to overview] | Proportion of Confirmed Tumor Responses Defined to be a Partial Response or Better Noted as the Objective Status on Two Consecutive Evaluations |
| NCT01794039 (4) [back to overview] | Time to Progression |
| NCT01794039 (4) [back to overview] | Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 |
| NCT01794039 (4) [back to overview] | Overall Survival |
| NCT01816971 (6) [back to overview] | Percentage of Participants With Progression-free Survival (PFS) |
| NCT01816971 (6) [back to overview] | Percentage of Participants With Overall Survival (OS) |
| NCT01816971 (6) [back to overview] | Time to Progression |
| NCT01816971 (6) [back to overview] | Percentage of Patients Achieving sCR |
| NCT01816971 (6) [back to overview] | Overall Response Rate, Defined as at Least a Partial Response to Therapy (> PR), at Least Very Good Partial Response (VGPR) and at Least Near Complete Response (nCR) Rate |
| NCT01816971 (6) [back to overview] | Duration of Response |
| NCT01850524 (20) [back to overview] | Cmax: Maximum Plasma Concentration for Ixazomib |
| NCT01850524 (20) [back to overview] | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) |
| NCT01850524 (20) [back to overview] | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score |
| NCT01850524 (20) [back to overview] | Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use |
| NCT01850524 (20) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT01850524 (20) [back to overview] | Time to Response |
| NCT01850524 (20) [back to overview] | Overall Survival (OS) |
| NCT01850524 (20) [back to overview] | Overall Response Rate (ORR) |
| NCT01850524 (20) [back to overview] | OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations |
| NCT01850524 (20) [back to overview] | Duration of Response |
| NCT01850524 (20) [back to overview] | Complete Response (CR) Rate |
| NCT01850524 (20) [back to overview] | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score |
| NCT01850524 (20) [back to overview] | Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry |
| NCT01850524 (20) [back to overview] | Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) |
| NCT01850524 (20) [back to overview] | PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations |
| NCT01850524 (20) [back to overview] | Time to Progression (TTP) |
| NCT01850524 (20) [back to overview] | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale |
| NCT01850524 (20) [back to overview] | Time to Pain Progression |
| NCT01850524 (20) [back to overview] | Progression Free Survival (PFS)-2 |
| NCT01850524 (20) [back to overview] | Progression Free Survival (PFS) |
| NCT01856192 (4) [back to overview] | Proportion of Patients With Response |
| NCT01856192 (4) [back to overview] | 3-year Progression-free Survival Rate |
| NCT01856192 (4) [back to overview] | Overall Survival Rate at 3 Years |
| NCT01856192 (4) [back to overview] | Proportion of Patients With Complete Response |
| NCT01881789 (6) [back to overview] | Duration of Response (DOR) |
| NCT01881789 (6) [back to overview] | Number of Participants With Dose-Limiting Toxicities (DLTs) |
| NCT01881789 (6) [back to overview] | Progression-Free Survival (PFS) |
| NCT01881789 (6) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (AEs) |
| NCT01881789 (6) [back to overview] | Plasma Oprozomib Concentration |
| NCT01881789 (6) [back to overview] | Overall Response Rate (ORR) |
| NCT01891643 (3) [back to overview] | Levels of CS1 Soluble Form (sCS1) in Serum |
| NCT01891643 (3) [back to overview] | Change From Baseline in the Levels of CS1 Soluble Form (sCS1) in Serum During Therapy and At Progression |
| NCT01891643 (3) [back to overview] | Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression |
| NCT01924169 (1) [back to overview] | Number of Participants With IgG Response |
| NCT01927718 (1) [back to overview] | Number of Participants With Response |
| NCT01938001 (10) [back to overview] | Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT) |
| NCT01938001 (10) [back to overview] | Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC) |
| NCT01938001 (10) [back to overview] | Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
| NCT01938001 (10) [back to overview] | Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC |
| NCT01938001 (10) [back to overview] | Kaplan-Meier Estimate of Overall Survival (OS) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Overall Survival (OS) |
| NCT01953692 (42) [back to overview] | Overall Survival (OS) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Overall Survival (OS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Progression-free Survival (PFS) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) |
| NCT01953692 (42) [back to overview] | Progression-free Survival (PFS) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Progression-free Survival (PFS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Progression-free Survival (PFS) in Participants Pooled From the Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Progression-free Survival (PFS) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Stringent Complete Remission (sCR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) |
| NCT01953692 (42) [back to overview] | Time to Progression (TTP) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Complete Remission Rate (CRR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Complete Response (CR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) |
| NCT01953692 (42) [back to overview] | Cytogenic Complete Response in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Cytogenic Partial Response in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Duration of Response (DOR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Duration of Response (DOR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) |
| NCT01953692 (42) [back to overview] | Duration of Response (DOR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D) |
| NCT01953692 (42) [back to overview] | Duration of Response (DOR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D) |
| NCT01953692 (42) [back to overview] | Erythroid Response in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Marrow Complete Response (mCR) in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Neutrophil Response in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) |
| NCT01953692 (42) [back to overview] | Number of Participants Who Experienced One or More Adverse Events (AEs): |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) |
| NCT01953692 (42) [back to overview] | Objective Response Rate (ORR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) |
| NCT01953692 (42) [back to overview] | Platelet Response in Cohort 1: Myelodysplastic Syndrome (MDS) |
| NCT02036502 (8) [back to overview] | Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment |
| NCT02036502 (8) [back to overview] | Duration of Response (DOR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment |
| NCT02036502 (8) [back to overview] | Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment |
| NCT02036502 (8) [back to overview] | Overall Survival (OS) |
| NCT02036502 (8) [back to overview] | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) |
| NCT02036502 (8) [back to overview] | Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment |
| NCT02036502 (8) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) |
| NCT02036502 (8) [back to overview] | Number of Participants Who Experienced One or More Adverse Events (AEs) |
| NCT02041325 (4) [back to overview] | Phenotypic Changes |
| NCT02041325 (4) [back to overview] | Safety |
| NCT02041325 (4) [back to overview] | Quantity of Subjects With a T-cell Response |
| NCT02041325 (4) [back to overview] | Positive for Hepatitis B Surface Antigen |
| NCT02076009 (9) [back to overview] | Time to Disease Progression (TTP) |
| NCT02076009 (9) [back to overview] | Time to Response |
| NCT02076009 (9) [back to overview] | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
| NCT02076009 (9) [back to overview] | Time to Subsequent Anticancer Treatment |
| NCT02076009 (9) [back to overview] | Duration of Response (DOR) |
| NCT02076009 (9) [back to overview] | Overall Response Rate |
| NCT02076009 (9) [back to overview] | Overall Survival (OS) |
| NCT02076009 (9) [back to overview] | Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better |
| NCT02076009 (9) [back to overview] | Progression-free Survival (PFS) |
| NCT02077166 (10) [back to overview] | Phase 2: Overall Survival (OS) |
| NCT02077166 (10) [back to overview] | Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs |
| NCT02077166 (10) [back to overview] | Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs |
| NCT02077166 (10) [back to overview] | Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) |
| NCT02077166 (10) [back to overview] | Phase 2: CR Rate |
| NCT02077166 (10) [back to overview] | Phase 2: Duration of Response (DOR) |
| NCT02077166 (10) [back to overview] | Phase 2: Overall Response Rate (ORR) |
| NCT02077166 (10) [back to overview] | Phase 2: Progression Free Survival (PFS) |
| NCT02077166 (10) [back to overview] | Phase 1b: Complete Response (CR) Rate |
| NCT02077166 (10) [back to overview] | Phase 1b: ORR |
| NCT02086552 (4) [back to overview] | Overall Survival |
| NCT02086552 (4) [back to overview] | Complete Response, Assessed Using the International Myeloma Working Group (IMWG) Uniform Response Criteria |
| NCT02086552 (4) [back to overview] | Progression-free Survival |
| NCT02086552 (4) [back to overview] | Progression-free Survival (1 Year Survival Rate) |
| NCT02126553 (4) [back to overview] | Complete Response (CR) Duration |
| NCT02126553 (4) [back to overview] | Event-free Survival (EFS) |
| NCT02126553 (4) [back to overview] | Overall Survival (OS) |
| NCT02126553 (4) [back to overview] | Relapse-free Survival (RFS) |
| NCT02128230 (1) [back to overview] | The Remission Rate for Participants With High-risk Myeloma |
| NCT02142049 (6) [back to overview] | Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR |
| NCT02142049 (6) [back to overview] | Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy |
| NCT02142049 (6) [back to overview] | Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy |
| NCT02142049 (6) [back to overview] | Number of Subjects With Adverse Events as a Measure of Safety and Tolerability |
| NCT02142049 (6) [back to overview] | Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability |
| NCT02142049 (6) [back to overview] | Duration of Response (DOR) |
| NCT02159365 (2) [back to overview] | Number of Participants With Any Grade and Grade 3 or Grade 4 (G3/4) Infusion Reactions Over the Entire Study Period |
| NCT02159365 (2) [back to overview] | Number of Participants With Grade 3 or Grade 4 (G3/4) Infusion Reactions by the End of Treatment Cycle 2 |
| NCT02225275 (3) [back to overview] | Number of Participants With a Response |
| NCT02225275 (3) [back to overview] | Time to Next Treatment |
| NCT02225275 (3) [back to overview] | Overall Survival |
| NCT02252172 (4) [back to overview] | Primary: Progression-free Survival (PFS) |
| NCT02252172 (4) [back to overview] | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12 |
| NCT02252172 (4) [back to overview] | Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12 |
| NCT02252172 (4) [back to overview] | Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12 |
| NCT02253316 (6) [back to overview] | Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms |
| NCT02253316 (6) [back to overview] | Number of Participants With Improvement in Minimal Residual Disease (MRD) |
| NCT02253316 (6) [back to overview] | MRD-negative Rate After ASCT |
| NCT02253316 (6) [back to overview] | Compare Response Rate Between the Two Maintenance Arms |
| NCT02253316 (6) [back to overview] | Toxicity of IRD Consolidation |
| NCT02253316 (6) [back to overview] | Response Rate of IRD Consolidation |
| NCT02265510 (10) [back to overview] | Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 |
| NCT02265510 (10) [back to overview] | Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793 |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 |
| NCT02265510 (10) [back to overview] | Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib |
| NCT02265510 (10) [back to overview] | Phase 2: Objective Response Rate (ORR) in Hematological Malignancies |
| NCT02265510 (10) [back to overview] | Phase 2: Number of Participants With at Least One TEAE and SAE |
| NCT02272803 (4) [back to overview] | Objective Response Rate (ORR) |
| NCT02272803 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT02272803 (4) [back to overview] | Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld) |
| NCT02272803 (4) [back to overview] | Progression Free Survival (PFS) Rate |
| NCT02279394 (4) [back to overview] | Overall Survival |
| NCT02279394 (4) [back to overview] | Time to Progression |
| NCT02279394 (4) [back to overview] | Percent of Patients Who Are Progression Free at 2 Years |
| NCT02279394 (4) [back to overview] | Objective Response Percent |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale |
| NCT02285062 (15) [back to overview] | K-M Estimate of Time to Next Lymphoma Therapy (TTNLT) |
| NCT02285062 (15) [back to overview] | Percentage of Participants Who Completed the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Health Related Quality of Life (HR-QoL) Questionnaire |
| NCT02285062 (15) [back to overview] | Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS) |
| NCT02285062 (15) [back to overview] | K-M Estimate of Overall Survival (OS) |
| NCT02285062 (15) [back to overview] | K-M Estimate of Duration of Complete Response |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale |
| NCT02285062 (15) [back to overview] | Percentage of Participants Who Achieved an Objective Response |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score |
| NCT02285062 (15) [back to overview] | Percentage of Participants Who Achieved a Complete Response (CR) |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI) |
| NCT02285062 (15) [back to overview] | Kaplan-Meier Estimate of Progression Free Survival (PFS) |
| NCT02285062 (15) [back to overview] | Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS) |
| NCT02285062 (15) [back to overview] | Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale |
| NCT02309515 (1) [back to overview] | Proportion of Participants With Successful Response |
| NCT02322320 (5) [back to overview] | Percentage of Participants With Event-free Survival (EFS) |
| NCT02322320 (5) [back to overview] | Percentage of Participants With Secondary Primary Malignancies (SPM) |
| NCT02322320 (5) [back to overview] | Percentage of Participants With Progression-free Survival (PFS) |
| NCT02322320 (5) [back to overview] | Percentage of Participants With Overall Survival (OS) |
| NCT02322320 (5) [back to overview] | Percentage of Participants With Disease Progression |
| NCT02331368 (3) [back to overview] | The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years |
| NCT02331368 (3) [back to overview] | The Estimated Percentage of Patients Alive at 2 Years |
| NCT02331368 (3) [back to overview] | The Number of Patients That Achieve Complete Response |
| NCT02335983 (13) [back to overview] | Change From Baseline in Hemoglobin Levels |
| NCT02335983 (13) [back to overview] | Change From Baseline in Neutrophil Count |
| NCT02335983 (13) [back to overview] | Change From Baseline in Platelet Count |
| NCT02335983 (13) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT02335983 (13) [back to overview] | Change From Baseline in Bilirubin |
| NCT02335983 (13) [back to overview] | Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group |
| NCT02335983 (13) [back to overview] | Progression-free Survival (PFS) |
| NCT02335983 (13) [back to overview] | Overall Response Rate (ORR) |
| NCT02335983 (13) [back to overview] | Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group |
| NCT02335983 (13) [back to overview] | Change From Baseline in Creatinine |
| NCT02335983 (13) [back to overview] | Duration of Response (DOR) |
| NCT02335983 (13) [back to overview] | Complete Response Rate (CRR) |
| NCT02335983 (13) [back to overview] | Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group |
| NCT02375555 (6) [back to overview] | Median Time to Response |
| NCT02375555 (6) [back to overview] | Grade 3 and 4 Treatment-Emergent Adverse Event (TEAE) Rate |
| NCT02375555 (6) [back to overview] | 4 Cycle Response Rate |
| NCT02375555 (6) [back to overview] | Successful Stem Cell Mobilization (SC Mob) Rate |
| NCT02375555 (6) [back to overview] | Objective Response Rate (ORR) at End of 8 Cycles of Induction Therapy. |
| NCT02375555 (6) [back to overview] | 4 Cycle Ever Dose Modification (DM) Rate |
| NCT02399085 (14) [back to overview] | Time to Progression (TTP) by IRC Evaluation |
| NCT02399085 (14) [back to overview] | Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs) |
| NCT02399085 (14) [back to overview] | Disease Control Rate (DCR) by IRC Evaluation |
| NCT02399085 (14) [back to overview] | DCR by INV Evaluation |
| NCT02399085 (14) [back to overview] | Duration of Response (DoR) by IRC Evaluation |
| NCT02399085 (14) [back to overview] | Time to Next Treatment (TTNT) |
| NCT02399085 (14) [back to overview] | Serum Drug Levels of MOR00208 |
| NCT02399085 (14) [back to overview] | Progression-free Survival (PFS) by IRC Evaluation |
| NCT02399085 (14) [back to overview] | PFS by INV Evaluation |
| NCT02399085 (14) [back to overview] | Overall Survival (OS) |
| NCT02399085 (14) [back to overview] | Number of Participants With Best Objective Response Rate (ORR) |
| NCT02399085 (14) [back to overview] | Event-free Survival (EFS) by IRC Evaluation |
| NCT02399085 (14) [back to overview] | DoR by Investigator (INV) Evaluation |
| NCT02399085 (14) [back to overview] | TTP by INV Evaluation |
| NCT02481934 (2) [back to overview] | Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization |
| NCT02481934 (2) [back to overview] | Number of Participants With Adverse Events During NKAE Treatment |
| NCT02492750 (2) [back to overview] | Number of Participants Experiencing a Dose-limiting Toxicity (DLT) |
| NCT02492750 (2) [back to overview] | Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0 |
| NCT02516696 (10) [back to overview] | Survival Duration Without Disease Progression |
| NCT02516696 (10) [back to overview] | Overall Survival |
| NCT02516696 (10) [back to overview] | Overall Response Rate |
| NCT02516696 (10) [back to overview] | Number of Patients With Objective Response Rate (CR+PR) |
| NCT02516696 (10) [back to overview] | Number of Patients With Complete Response Rate (CR) |
| NCT02516696 (10) [back to overview] | Number of Days for Event-Free Survival |
| NCT02516696 (10) [back to overview] | Number of Days for Duration of Response |
| NCT02516696 (10) [back to overview] | Number of Days After Initiating Treatment With BiRd Regimen to Disease Progression, as Compared to Subjects on Rd Treatment Regimen. |
| NCT02516696 (10) [back to overview] | Number of Adverse Events Experienced |
| NCT02516696 (10) [back to overview] | Functional Assessment of Chronic Illness Therapy - Fatigue Subscale (FS; Version 4) Score of Patients Receiving BiRd vs Rd Treatment |
| NCT02538965 (13) [back to overview] | Apparent Total Clearance (CL/F) of Lenalidomide |
| NCT02538965 (13) [back to overview] | Apparent Volume of Distribution (Vz/F) of Lenalidomide |
| NCT02538965 (13) [back to overview] | Area Under the Plasma Concentration Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0∞) Of Lenalidomide |
| NCT02538965 (13) [back to overview] | Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Lenalidomide (AUC-t) |
| NCT02538965 (13) [back to overview] | Number of Participants Who Achieved a Best Response of Morphologic Complete Remission, Morphologic Complete Remission Incomplete or Partial Remission |
| NCT02538965 (13) [back to overview] | Maximum Observed Concentration (Cmax) of Lenalidomide |
| NCT02538965 (13) [back to overview] | Number of Participants Who Achieved a Morphologic Complete Response Within the First Four Cycles of Lenalidomide Treatment According to the Modified International Working Group (IWG) Criteria |
| NCT02538965 (13) [back to overview] | Percentage of Participants With of Graft Versus Host Disease (GVHD) |
| NCT02538965 (13) [back to overview] | Terminal Half-Life (t1/2) of Lenalidomide |
| NCT02538965 (13) [back to overview] | Time to Reach Maximum Concentration (Tmax) of Lenalidomide |
| NCT02538965 (13) [back to overview] | Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE) |
| NCT02538965 (13) [back to overview] | Number of Participants Who Received a Haematopoietic Stem Cell Transplant (HSCT) |
| NCT02538965 (13) [back to overview] | Number of Participants With a Morphologic CR, CRi, PR or Treatment Failure at Cycles 1, 2 and 3 |
| NCT02561273 (7) [back to overview] | Number of Participants With Adverse Events Graded According to CTC (Phase II) |
| NCT02561273 (7) [back to overview] | Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I) |
| NCT02561273 (7) [back to overview] | Progression-free Survival |
| NCT02561273 (7) [back to overview] | Overall Survival |
| NCT02561273 (7) [back to overview] | Overall Response Rate |
| NCT02561273 (7) [back to overview] | Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP |
| NCT02561273 (7) [back to overview] | Complete Response Rate (Phase II) |
| NCT02579863 (7) [back to overview] | Overall Survival (OS) |
| NCT02579863 (7) [back to overview] | Number of Participants Who Experienced One or More Adverse Events (AEs) |
| NCT02579863 (7) [back to overview] | Number of Participants Discontinuing Study Treatment Due to an AE |
| NCT02579863 (7) [back to overview] | Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review |
| NCT02579863 (7) [back to overview] | Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review |
| NCT02579863 (7) [back to overview] | Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review |
| NCT02579863 (7) [back to overview] | Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Adverse Events (AEs) |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans |
| NCT02600897 (34) [back to overview] | Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone |
| NCT02600897 (34) [back to overview] | Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans |
| NCT02600897 (34) [back to overview] | Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Dose-Limiting Toxicities (DLTs) |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone |
| NCT02600897 (34) [back to overview] | Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone |
| NCT02600897 (34) [back to overview] | Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin |
| NCT02600897 (34) [back to overview] | Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab |
| NCT02600897 (34) [back to overview] | Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab |
| NCT02600897 (34) [back to overview] | Observed Plasma Lenalidomide Concentration |
| NCT02600897 (34) [back to overview] | Observed Plasma Lenalidomide Concentration |
| NCT02600897 (34) [back to overview] | Observed Serum Obinutuzumab Concentration |
| NCT02600897 (34) [back to overview] | Observed Serum Obinutuzumab Concentration |
| NCT02600897 (34) [back to overview] | Observed Serum Obinutuzumab Concentration |
| NCT02600897 (34) [back to overview] | Observed Serum Obinutuzumab Concentration |
| NCT02600897 (34) [back to overview] | Observed Serum Rituximab Concentration |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE) |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
| NCT02600897 (34) [back to overview] | Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE |
| NCT02600897 (34) [back to overview] | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody |
| NCT02600897 (34) [back to overview] | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody |
| NCT02600897 (34) [back to overview] | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody |
| NCT02600897 (34) [back to overview] | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody |
| NCT02600897 (34) [back to overview] | Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody |
| NCT02619682 (3) [back to overview] | Disease Free Survival |
| NCT02619682 (3) [back to overview] | Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0 |
| NCT02619682 (3) [back to overview] | Overall Survival |
| NCT02631577 (15) [back to overview] | Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment |
| NCT02631577 (15) [back to overview] | Serum Concentration of Obinutuzumab (mcg/mL) |
| NCT02631577 (15) [back to overview] | Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria |
| NCT02631577 (15) [back to overview] | Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab |
| NCT02631577 (15) [back to overview] | Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria |
| NCT02631577 (15) [back to overview] | Percentage of Participants With Adverse Events and Serious Adverse Events |
| NCT02631577 (15) [back to overview] | Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone |
| NCT02631577 (15) [back to overview] | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone |
| NCT02631577 (15) [back to overview] | Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans |
| NCT02631577 (15) [back to overview] | Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab |
| NCT02631577 (15) [back to overview] | Serum Concentration of Atezolizumab (mcg/mL) |
| NCT02631577 (15) [back to overview] | Serum Concentration of Lenalidomide (ng/mL) |
| NCT02631577 (15) [back to overview] | Serum Concentration of Obinutuzumab (mcg/mL) |
| NCT02631577 (15) [back to overview] | Serum Concentration of Atezolizumab (mcg/mL) |
| NCT02631577 (15) [back to overview] | Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Time to Maximum Observed Concentration (Tmax) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Time to Maximum Observed Concentration (Tmax) |
| NCT02685826 (26) [back to overview] | Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT02685826 (26) [back to overview] | Time to Response (for Cohorts A and B) |
| NCT02685826 (26) [back to overview] | Response Improvement Rate (RIR) for Cohort C: Percentage of Participants Achieving a Response Improved From Cycle 1 Day 1 as Assessed by the Investigators Using the International Myeloma Working Group (IMWG) Uniform Response Criteria |
| NCT02685826 (26) [back to overview] | Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28) |
| NCT02685826 (26) [back to overview] | Participants Who Had Either Disease Progression or Death |
| NCT02685826 (26) [back to overview] | Participants Who Died Up To Data Cut-off Date (15 December 2017) |
| NCT02685826 (26) [back to overview] | Participants Who Developed Anti-drug Antibody Against Durvalumab |
| NCT02685826 (26) [back to overview] | Overall Response Rate (ORR) for Cohorts A and B: Percentage of Participants Who Achieved a Partial Response or Better According to the International Myeloma Working Group (IMWG) Uniform Response Criteria |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma PK Parameters in Cycle 1 Day 15: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Maximum Observed Concentration (Cmax) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Time to Maximum Observed Concentration (Tmax) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Terminal Elimination Half-life (t1/2) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Maximum Observed Concentration (Cmax) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Volume of Distribution (Vz/F) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum Pharmacokinetic (PK) Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Clearance (CL) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Maximum Observed Concentration (Cmax) |
| NCT02685826 (26) [back to overview] | Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Clearance (CL/F) |
| NCT02685826 (26) [back to overview] | Kaplan-Meier Estimates for Duration of Response (for Cohort A and B) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Volume of Distribution (Vz) |
| NCT02685826 (26) [back to overview] | Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Terminal Elimination Half-life (t1/2) |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Progression-Free Survival in Pairwise Analysis |
| NCT02728102 (15) [back to overview] | Number of Grade ≥ 3 Toxicities |
| NCT02728102 (15) [back to overview] | Percentage of Participants With 1-year Response Rate of CR/sCR |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Grade 2 and 3 Infections |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Treatment-related Mortality (TRM) |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms |
| NCT02728102 (15) [back to overview] | Participants With Grade ≥ 3 Toxicities |
| NCT02728102 (15) [back to overview] | Participants Response to Treatment |
| NCT02728102 (15) [back to overview] | Number of Participants With Minimal Residual Disease (MRD) |
| NCT02728102 (15) [back to overview] | Number of Grade 2 and 3 Infections |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Progression-Free Survival |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Overall Survival in Pairwise Analysis |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Overall Survival |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Myeloma Progression in Pairwise Analysis |
| NCT02728102 (15) [back to overview] | Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis |
| NCT02733042 (21) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib |
| NCT02733042 (21) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab |
| NCT02733042 (21) [back to overview] | Time to First Response |
| NCT02733042 (21) [back to overview] | Time to Maximum Plasma Concentration (Tmax) of Durvalumab |
| NCT02733042 (21) [back to overview] | Volume of Distribution (Vz) of Durvalumab |
| NCT02733042 (21) [back to overview] | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide |
| NCT02733042 (21) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib |
| NCT02733042 (21) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab |
| NCT02733042 (21) [back to overview] | Kaplan-Meier Estimate of Progression-free Survival (PFS) |
| NCT02733042 (21) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Durvalumab |
| NCT02733042 (21) [back to overview] | Kaplan-Meier Estimate of Duration of Response |
| NCT02733042 (21) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide |
| NCT02733042 (21) [back to overview] | Clearance (CL) of Durvalumab |
| NCT02733042 (21) [back to overview] | Number of Participants With Treatment-emergent Adverse Events |
| NCT02733042 (21) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection |
| NCT02733042 (21) [back to overview] | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib |
| NCT02733042 (21) [back to overview] | Terminal Elimination Phase Half-Life (t½) of Durvalumab |
| NCT02733042 (21) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide |
| NCT02733042 (21) [back to overview] | Overall Response Rate (ORR) During Durvalumab Treatment |
| NCT02733042 (21) [back to overview] | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
| NCT02733042 (21) [back to overview] | Overall Response Rate During the Entire Study |
| NCT02843074 (8) [back to overview] | Maintenance Feasibility Rate (MFR) |
| NCT02843074 (8) [back to overview] | Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety |
| NCT02843074 (8) [back to overview] | Complete Response Rate (CRR) for Complete Time on Study |
| NCT02843074 (8) [back to overview] | Overall Survival (OS) |
| NCT02843074 (8) [back to overview] | Progression-free Survival (PFS) |
| NCT02843074 (8) [back to overview] | Consolidation Feasibility Rate (CFR) |
| NCT02843074 (8) [back to overview] | Induction Feasibility Rate (IFR) |
| NCT02843074 (8) [back to overview] | Overall Response Rate (ORR) for Complete Time on Study |
| NCT02874742 (16) [back to overview] | Percentage of Participants With Overall Stringent Complete Response (sCR) |
| NCT02874742 (16) [back to overview] | Percentage of Participants With Overall Response Rate (ORR) |
| NCT02874742 (16) [back to overview] | Duration of Complete Response or Better |
| NCT02874742 (16) [back to overview] | Duration of Response |
| NCT02874742 (16) [back to overview] | Duration of Stringent Complete Response (sCR) |
| NCT02874742 (16) [back to overview] | Overall Survival (OS) |
| NCT02874742 (16) [back to overview] | Percentage of Participants With Stringent Complete Response (sCR) |
| NCT02874742 (16) [back to overview] | Progression-free Survival (PFS) |
| NCT02874742 (16) [back to overview] | Time to Complete Response or Better |
| NCT02874742 (16) [back to overview] | Time to Partial Response (PR) or Better |
| NCT02874742 (16) [back to overview] | Time to Progression (TTP) |
| NCT02874742 (16) [back to overview] | Time to Stringent Complete Response (sCR) |
| NCT02874742 (16) [back to overview] | Time to Very Good Partial Response (VGPR) or Better |
| NCT02874742 (16) [back to overview] | Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better |
| NCT02874742 (16) [back to overview] | Percentage of Participants With Complete Response (CR) or Better |
| NCT02874742 (16) [back to overview] | Percentage of Participants With Negative Minimal Residual Disease (MRD) |
| NCT02880228 (5) [back to overview] | Progression-free Survival |
| NCT02880228 (5) [back to overview] | Proportion of Complete Response Plus Very Good Partial Response (VGPR) |
| NCT02880228 (5) [back to overview] | Proportion of Successful Stem Cell Collection |
| NCT02880228 (5) [back to overview] | Survival Time |
| NCT02880228 (5) [back to overview] | Partial Response (PR) |
| NCT02898259 (7) [back to overview] | Duration of Response |
| NCT02898259 (7) [back to overview] | Maximum Tolerated Dose (MTD) of Oral Ixazomib |
| NCT02898259 (7) [back to overview] | Overall Survival |
| NCT02898259 (7) [back to overview] | Progression Free Survival |
| NCT02898259 (7) [back to overview] | Time to Progression |
| NCT02898259 (7) [back to overview] | Time to Treatment Failure |
| NCT02898259 (7) [back to overview] | Overall Response Rate |
| NCT02903381 (8) [back to overview] | Number of Participants With Adverse Events |
| NCT02903381 (8) [back to overview] | Objective Response Percent |
| NCT02903381 (8) [back to overview] | Progression Free Survival (PFS) Probability at 2-years |
| NCT02903381 (8) [back to overview] | Progression Free Survival Rate-Without Cyclophosphamide |
| NCT02903381 (8) [back to overview] | Time to Progression Probability at 2-years |
| NCT02903381 (8) [back to overview] | Overall Survival Probability at 2-years |
| NCT02903381 (8) [back to overview] | 2 Year Progression Free Percent |
| NCT02903381 (8) [back to overview] | Duration of Response Probability at 2-years |
| NCT02906332 (4) [back to overview] | Evaluation of Stringent Complete Response, Complete Response, and Very Good Partial Response Rate (sCR + CR + VGPR Rate). |
| NCT02906332 (4) [back to overview] | Number of Participants Serious Adverse Events |
| NCT02906332 (4) [back to overview] | Number of Participants Who Progressed at 12 Months |
| NCT02906332 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT02917941 (9) [back to overview] | Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related Laboratory Parameters |
| NCT02917941 (9) [back to overview] | Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) |
| NCT02917941 (9) [back to overview] | Overall Response Rate (ORR) |
| NCT02917941 (9) [back to overview] | Overall Survival (OS) |
| NCT02917941 (9) [back to overview] | Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR) |
| NCT02917941 (9) [back to overview] | Duration of Response (DOR) |
| NCT02917941 (9) [back to overview] | Time to Progression (TTP) |
| NCT02917941 (9) [back to overview] | Progression-free Survival (PFS) |
| NCT02917941 (9) [back to overview] | Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related to Vital Signs |
| NCT02954406 (8) [back to overview] | Dose Escalation Phase: Maximum Tolerated Dose (MTD) of TAK-659 |
| NCT02954406 (8) [back to overview] | Time to Progression (TTP) |
| NCT02954406 (8) [back to overview] | Tmax: Time to Reach the Maximum Plasma Concentration for TAK-659 |
| NCT02954406 (8) [back to overview] | Cmax: Maximum Observed Plasma Concentration for TAK-659 |
| NCT02954406 (8) [back to overview] | Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of TAK-659 |
| NCT02954406 (8) [back to overview] | AUCtau: Area Under the Plasma Concentration-time Curve During Dosing Interval |
| NCT02954406 (8) [back to overview] | Overall Response Rate (ORR) |
| NCT02954406 (8) [back to overview] | Duration of Response (DOR) |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018) |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density |
| NCT03003520 (8) [back to overview] | Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells |
| NCT03003520 (8) [back to overview] | Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT03003520 (8) [back to overview] | Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT03019640 (2) [back to overview] | Treatment-related Mortality Within 30 Days (TRM30) |
| NCT03019640 (2) [back to overview] | Number of Participants Who Survived |
| NCT03050450 (3) [back to overview] | Total Number of Adverse Events |
| NCT03050450 (3) [back to overview] | Best Response of Children With Recurrent or Refractory Central Nervous System Tumors |
| NCT03050450 (3) [back to overview] | Number Participants With Hematologic and Non-hematologic Toxicities |
| NCT03118466 (6) [back to overview] | Transfusion Support: Number of Red Blood Cell and Platelet Transfusions |
| NCT03118466 (6) [back to overview] | Treatment-related Mortality |
| NCT03118466 (6) [back to overview] | Overall Survival |
| NCT03118466 (6) [back to overview] | Number of Patients That Achieved Platelet Recovery |
| NCT03118466 (6) [back to overview] | Number of Patients That Achieved ANC Recovery |
| NCT03118466 (6) [back to overview] | Complete Response Rate |
| NCT03224507 (8) [back to overview] | Overall Survival |
| NCT03224507 (8) [back to overview] | Percentage of Patients Achieving Complete Remission Following Complete Therapy |
| NCT03224507 (8) [back to overview] | Serious Adverse Events (SAEs) From the KRdD Treatment |
| NCT03224507 (8) [back to overview] | Percentage of Patients With MRD(-) Status at the Completion of Induction Therapy |
| NCT03224507 (8) [back to overview] | Progression-free Survival |
| NCT03224507 (8) [back to overview] | Percentage of Patients With MRD(-) Remissions at the Completion of Consolidation Therapy |
| NCT03224507 (8) [back to overview] | Percentage of Patients With Auto-HCT That Convert From Positive to Negative MRD |
| NCT03224507 (8) [back to overview] | Percentage of Patients That Convert From MRD(-) to MRD(+) Following Treatment Discontinuation |
| NCT03411031 (3) [back to overview] | Overall Response |
| NCT03411031 (3) [back to overview] | Minimum Response (MR) |
| NCT03411031 (3) [back to overview] | Percentage of Participants With Progression Free Survival (PFS) |
| NCT03412565 (14) [back to overview] | Percentage of Participants With Anti-Daratumumab Antibodies |
| NCT03412565 (14) [back to overview] | D-VRd Cohort: Overall Response Rate (ORR) |
| NCT03412565 (14) [back to overview] | D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response |
| NCT03412565 (14) [back to overview] | D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate |
| NCT03412565 (14) [back to overview] | D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response |
| NCT03412565 (14) [back to overview] | Percentage of Participants With Infusion-Related Reactions (IRRs) |
| NCT03412565 (14) [back to overview] | Maximum Observed Serum Concentration (Cmax) of Daratumumab |
| NCT03412565 (14) [back to overview] | Maximum Observed Serum Concentration (Cmax) of Daratumumab |
| NCT03412565 (14) [back to overview] | Maximum Observed Serum Concentration (Cmax) of Daratumumab |
| NCT03412565 (14) [back to overview] | Maximum Observed Serum Concentration (Cmax) of Daratumumab |
| NCT03412565 (14) [back to overview] | D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR) |
| NCT03412565 (14) [back to overview] | D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR) |
| NCT03412565 (14) [back to overview] | Percentage of Participants With CR or Better Response |
| NCT03412565 (14) [back to overview] | Percentage of Participants With Anti-rHuPH20 Antibodies |
| NCT03416374 (21) [back to overview] | Percentage of Participants With Bone Lesions (Bone Evaluation) |
| NCT03416374 (21) [back to overview] | Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) |
| NCT03416374 (21) [back to overview] | Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment |
| NCT03416374 (21) [back to overview] | Overall Survival (OS) From the Start of Study Treatment |
| NCT03416374 (21) [back to overview] | Overall Response Rate (ORR) |
| NCT03416374 (21) [back to overview] | Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) |
| NCT03416374 (21) [back to overview] | Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month |
| NCT03416374 (21) [back to overview] | Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants |
| NCT03416374 (21) [back to overview] | Duration of Therapy (DOT) |
| NCT03416374 (21) [back to overview] | Duration of Response (DOR) |
| NCT03416374 (21) [back to overview] | Evaluation of Modified Quality-Adjusted Life-Years (QALYs) |
| NCT03416374 (21) [back to overview] | Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR |
| NCT03416374 (21) [back to overview] | Time to Next Treatment (TTNT) |
| NCT03416374 (21) [back to overview] | Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment |
| NCT03416374 (21) [back to overview] | PFS From the Start of Study Treatment |
| NCT03416374 (21) [back to overview] | Percentage of Participants Who Achieve or Maintain Any Best Response |
| NCT03416374 (21) [back to overview] | Relative Dose Intensity (RDI) |
| NCT03416374 (21) [back to overview] | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score |
| NCT03416374 (21) [back to overview] | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score |
| NCT03416374 (21) [back to overview] | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) |
| NCT03416374 (21) [back to overview] | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) |
| NCT03433001 (15) [back to overview] | Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) |
| NCT03433001 (15) [back to overview] | Overall Response Rate (ORR) |
| NCT03433001 (15) [back to overview] | Overall Survival (OS) |
| NCT03433001 (15) [back to overview] | Percentage of Participants Who Achieve VGPR or Better (CR+VGPR) |
| NCT03433001 (15) [back to overview] | Percentage of Participants With Bone Lesions (Bone Evaluation) |
| NCT03433001 (15) [back to overview] | Time to Next Treatment (TTNT) |
| NCT03433001 (15) [back to overview] | Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global Health Status Score |
| NCT03433001 (15) [back to overview] | Relative Dose Intensity (RDI) |
| NCT03433001 (15) [back to overview] | Percentage of Participants Who Achieve or Maintain Any Best Response |
| NCT03433001 (15) [back to overview] | Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment |
| NCT03433001 (15) [back to overview] | Progression-Free Survival (PFS) |
| NCT03433001 (15) [back to overview] | Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score |
| NCT03433001 (15) [back to overview] | Duration of Therapy (DOT) |
| NCT03433001 (15) [back to overview] | Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR |
| NCT03433001 (15) [back to overview] | PFS Rate at 12 Months and 24 Months After the Start of Treatment |
| NCT04272775 (8) [back to overview] | Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR) |
| NCT04272775 (8) [back to overview] | Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) |
| NCT04272775 (8) [back to overview] | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) |
| NCT04272775 (8) [back to overview] | Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities |
| NCT04272775 (8) [back to overview] | Cmax: Maximum Observed Plasma Concentration for Ixazomib |
| NCT04272775 (8) [back to overview] | Number of Participants With Grade 3 or Higher TEAE Related to Vital Signs |
| NCT04272775 (8) [back to overview] | Number of Participants With Grade 3 or Higher TEAE Related to Body Weight |
| NCT04272775 (8) [back to overview] | Number of Participants With Grade 3 or Higher TEAE Related to 12-lead Electrocardiograms (ECGs) |
| NCT04430894 (9) [back to overview] | Overall Response Rate After 4 Cycles Induction Therapy |
| NCT04430894 (9) [back to overview] | Minimal Residual Disease (MRD) Rate at 10^(-5) in Patients Receiving Upfront Stem Cell Transplant |
| NCT04430894 (9) [back to overview] | Minimal Residual Disease (MRD) Rate at 10^(-5) in Patients Deferring Stem Cell Transplant |
| NCT04430894 (9) [back to overview] | Complete Response Rate in Patients With Upfront Stem Cell Transplant |
| NCT04430894 (9) [back to overview] | Complete Response (CR + Stringent CR) Rate |
| NCT04430894 (9) [back to overview] | Overall Survival at 12 Months |
| NCT04430894 (9) [back to overview] | Progression Free Survival at 12 Months |
| NCT04430894 (9) [back to overview] | Minimal Residual Disease (MRD) Rate After 4 Cycles Induction Therapy |
| NCT04430894 (9) [back to overview] | Complete Response Rate in Patients Deferring Stem Cell Transplant |
[back to top]
Time to Tumor Progression (TTP)
Time to progression (TTP) was calculated as the time from randomization to the first documentation of progressive disease based on the myeloma response determination criteria developed by Bladé et. al., Br J Haematol 1998; 102:1115-1123. (NCT00056160)
Timeframe: 60 weeks (median Time To Progression of CC-5013/Dex treatment group)
| Intervention | Weeks (Median) |
|---|
| CC-5013/Dex | 60.1 |
| Placebo/Dex | 20.1 |
Myeloma Response
The overall confirmed response that was maintained for ≥6 weeks. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens. (NCT00056160)
Timeframe: Up to Unblinding (07 Jun 2005)
| Intervention | Participants (Number) |
|---|
| CC-5013/Dex | 107 |
| Placebo/Dex | 34 |
Overall Survival
Overall survival was calculated as the time from randomization to death from any cause. (NCT00056160)
Timeframe: 170 weeks (median overall survival of CC-5013/Dex treatment group)
| Intervention | Weeks (Median) |
|---|
| CC-5013/Dex | 170.1 |
| Placebo/Dex | 136.4 |
Progression-Free Survival
"Progression is defined as a > 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc.~In patients with a confirmed Partial Remission, Remission, or Complete Remission, relapse is defined as the first occurrence of any of the following: 1) a myeloma protein increase by than 100% from the lowest level recorded on study, provided the absolute magnitude of this increase is at least 1g/dL for a serum monoclonal protein or at least 500 mg/24 hrs of urine M-protein; 2) a myeloma protein increase above the response criteria for Partial Remission, with the same requirements for the absolute magnitude of the protein increase; 3)reappearance of any myeloma peak that had disappeared while on protocol treatment, provided it meets the same requirements listed above; 4) increase in the size and number of lytic bone lesions recognized on radiographs." (NCT00064038)
Timeframe: From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide+Dexamethasone | 78 |
| Dexamethasone | 52 |
Toxicity
Compare the toxicity profile of these regimens, including thrombotic complications, in these patients, based on CTCAE v. 3.0. (NCT00064038)
Timeframe: From time of initiating study treatment until discontinuation of study treatment or of open-label REVLIMID + LOW DOSE DEX, whichever comes last, up to 5 years
| Intervention | Participants (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT | Albumin, serum-low (hypoalbuminemia) | Anorexia | Apnea | Arthritis (non-septic) | Aspiration | Ataxia (incoordination) | Bilirubin (hyperbilirubinemia) | CNS cerebrovascular ischemia | Calcium, serum-high (hypercalcemia) | Calcium, serum-low (hypocalcemia) | Cardiopulmonary arrest, cause unknown (non-fatal) | Cataract | Cognitive disturbance | Colitis | Colitis, infectious (e.g., Clostridium difficile) | Confusion | Constipation | Creatinine | Cystitis | Dehydration | Dermatology/Skin-Other (Specify) | Diarrhea | Dizziness | Dyspnea (shortness of breath) | Edema: limb | Encephalopathy | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Fever in absence of neutropenia, ANC lt1.0x10e9/L | Fracture | Gastritis (including bile reflux gastritis) | Gastrointestinal-Other (Specify) | Glomerular filtration rate | Glucose, serum-high (hyperglycemia) | Glucose, serum-low (hypoglycemia) | Heartburn/dyspepsia | Hemoglobin | Hemorrhage, CNS | Hemorrhage, GI - Colon | Hypertension | Hypotension | Hypoxia | INR (of prothrombin time) | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | Inf w/normal ANC or Gr 1-2 neutrophils - Bladder | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | Inf w/normal ANC or Gr 1-2 neutrophils - Colon | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | Inf w/normal ANC or Gr 1-2 neutrophils - Wound | Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran | Infection with unknown ANC - Lung (pneumonia) | Infection with unknown ANC - Upper airway NOS | Infection-Other (Specify) | Insomnia | Joint-function | Left ventricular diastolic dysfunction | Left ventricular systolic dysfunction | Leukocytes (total WBC) | Lymphopenia | Mood alteration - agitation | Mood alteration - anxiety | Mood alteration - depression | Mucositis/stomatitis (clinical exam) - Oral cavity | Muscle weakness, not d/t neuropathy - Extrem-lower | Muscle weakness, not d/t neuropathy - body/general | Musculoskeletal/Soft Tissue-Other (Specify) | Nausea | Neuropathy: motor | Neuropathy: sensory | Neutrophils/granulocytes (ANC/AGC) | Ocular/Visual-Other (Specify) | Ophthalmoplegia/diplopia (double vision) | Opportunistic inf associated w/gt=Gr 2 lymphopenia | PTT (Partial thromboplastin time) | Pain - Abdomen NOS | Pain - Back | Pain - Bladder | Pain - Bone | Pain - Extremity-limb | Pain - Head/headache | Pain - Joint | Pain - Muscle | Pain - Pain NOS | Pain - Stomach | Pain-Other (Specify) | Pancreatic endocrine: glucose intolerance | Perforation, GI - Colon | Perforation, GI - Small bowel NOS | Phosphate, serum-low (hypophosphatemia) | Platelets | Pneumonitis/pulmonary infiltrates | Potassium, serum-low (hypokalemia) | Prolonged QTc interval | Proteinuria | Pulmonary/Upper Respiratory-Other (Specify) | Rash/desquamation | Rash: acne/acneiform | Rash: erythema multiforme | Renal failure | SVT and nodal arrhythmia - Atrial fibrillation | Sodium, serum-high (hypernatremia) | Sodium, serum-low (hyponatremia) | Somnolence/depressed level of consciousness | Speech impairment (e.g., dysphasia or aphasia) | Syncope (fainting) | Thrombosis/embolism (vascular access-related) | Thrombosis/thrombus/embolism | Thrombotic microangiopathy | Thyroid function, low (hypothyroidism) | Tinnitus | Vision-blurred vision | Vomiting | Weight loss |
|---|
| Crossover to Rev+Dex | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 3 | 0 | 2 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 3 | 0 | 1 | 2 | 0 | 2 | 1 | 8 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 6 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 4 | 8 | 1 | 0 | 2 | 0 | 1 | 3 | 0 | 0 | 0 | 0 | 7 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 3 | 2 | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 0 | 0 | 3 | 1 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 1 | 0 | 1 |
,| Dexamethasone | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 1 | 1 | 2 | 1 | 0 | 12 | 0 | 1 | 1 | 0 | 0 | 0 | 18 | 0 | 1 | 5 | 0 | 0 | 3 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 1 | 3 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 1 | 6 | 0 | 0 | 0 | 5 | 5 | 1 | 1 | 8 | 1 | 3 | 4 | 2 | 1 | 1 | 4 | 6 | 0 | 1 | 0 | 1 | 2 | 2 | 0 | 3 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 4 | 4 | 2 | 2 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 3 | 1 | 0 |
,| Lenalidomide and Dexamethasone | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 7 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 5 | 1 | 4 | 0 | 0 | 19 | 1 | 1 | 0 | 0 | 1 | 0 | 5 | 1 | 0 | 6 | 1 | 1 | 0 | 3 | 4 | 1 | 1 | 1 | 5 | 1 | 1 | 2 | 0 | 1 | 1 | 2 | 2 | 3 | 1 | 0 | 1 | 1 | 0 | 4 | 1 | 0 | 1 | 14 | 10 | 1 | 1 | 11 | 0 | 1 | 9 | 0 | 2 | 0 | 3 | 21 | 1 | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 3 | 3 | 1 | 0 | 0 | 0 | 1 | 0 | 5 | 7 | 3 | 6 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 1 | 2 | 19 | 1 | 1 | 1 | 2 | 2 | 0 |
Participants With Bone Marrow Progression
"Bone marrow aspirate was assessed by a central reviewer. Progression is represented in two categories according to changes from baseline in French-American-British (FAB) classification (see Baseline Characteristics):~Baseline classification of refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) to a during treatment (plus 30 days) classification of refractory anemia with excess blasts (RAEB).~Any baseline FAB classification to a during treatment (plus 30 days) classification of acute myeloid leukemia (AML)." (NCT00065156)
Timeframe: up to 2 years
| Intervention | participants (Number) |
|---|
| RA/RARS to RAEB | RA/RARS/RAEB/CMML to AML |
|---|
| Lenalidomide | 11 | 6 |
Participants Who Achieved Red Blood Cell (RBC) -Transfusion Independence
"Number of participants who achieved RBC-transfusion independence, which was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive rolling 56 days during the treatment period (eg, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin." (NCT00065156)
Timeframe: Up to 2 years
| Intervention | participants (Number) |
|---|
| Lenalidomide | 59 |
Participants Who Relapsed or Maintained Their Transfusion Independence After Achieving Transfusion Independence During the Study
"Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive rolling 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Participants who relapsed required a transfusion after the period of transfusion independence. Participants who maintained transfusion independence did not require a transfusion during the remainder of the study." (NCT00065156)
Timeframe: up to 2 years
| Intervention | participants (Number) |
|---|
| Relapsed (had a transfusion after response) | Maintained transfusion independence |
|---|
| Lenalidomide | 35 | 24 |
Participant Counts of Platelet Response
"Major platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3 in all values within 56 days of start of treatment, an absolute increase of ≥30,000/mm^3 sustained for ≥56 consecutive days. In platelet transfusion-dependent participants, a major response was stabilization of platelet counts and platelet transfusion independence.~Minor platelet response: participants with a minimum pretreatment platelet of <100,000/mm^3, a ≥ 50% increase in platelet count with a net increase >10,000/mm^3 for a consecutive 56-day period in the absence of platelet transfusions." (NCT00065156)
Timeframe: up to 2 years
| Intervention | participants (Number) |
|---|
| Major | Minor | None |
|---|
| Lenalidomide | 2 | 0 | 13 |
Participant Counts of Cytogenetic Response
"Participants deemed evaluable by the central cytogenetic review had their cytogenetic response categorized as major or minor. A major cytogenetic response was defined as ≥ 20 metaphases recorded at baseline, and at least~1 post baseline evaluation with ≥ 20 metaphases analyzed with no abnormal metaphases observed. A minor cytogenetic response was defined as ≥ 20 metaphases analyzed at baseline, and at least 1 post baseline evaluation with ≥ 20 metaphases analyzed with a ≥ 50% reduction in the proportion of hematopoietic cells with cytogenetic abnormalities compared with baseline." (NCT00065156)
Timeframe: up to 2 years
| Intervention | participants (Number) |
|---|
| Major | Minor | None |
|---|
| Lenalidomide | 18 | 20 | 14 |
Participants With Adverse Experiences
"Counts of study participants who had adverse events (AEs) during the study. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.~The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE." (NCT00065156)
Timeframe: Up to 2 Years
| Intervention | participants (Number) |
|---|
| At least one AE | At least one AE related to study drug | At least one NCI CTC grade 3-4 AE | At least one NCI CTC grade 3-4 AE related to drug | At least one serious AE | At least one serious AE related to study drug | AE leading to dose reduction or interruption | AE leading to discontinuation of study drug |
|---|
| Lenalidomide | 148 | 143 | 140 | 131 | 89 | 40 | 131 | 47 |
Participant Counts of Absolute Neutrophil Count (ANC) Response
"Major neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3 in all values obtained within 56 days of start of treatment, a ≥ 100% increase or an absolute increase of~≥ 500/mm^3, whichever was greater (at least to be ≥ 500/mm^3), sustained for 56 consecutive days. Minor neutrophil response: participants with a minimum pretreatment ANC concentration of < 1500/mm^3, an increase in ANC concentration of ≥ 100% sustained for 56 consecutive days." (NCT00065156)
Timeframe: up to 2 years
| Intervention | participant (Number) |
|---|
| Major | Minor | None |
|---|
| Lenalidomide | 9 | 0 | 18 |
Participants With a >= 50% Decrease From Baseline in Red Blood Cell (RBC) Transfusion Requirements Over Any Consecutive 56 Days During Study
A participant was categorized as having a transfusion reduction response if there was a ≥ 50% decrease from pretreatment transfusion requirements (before the start of the study mediation) compared to any consecutive 56 days during the study (i.e. post treatment). (NCT00065156)
Timeframe: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
| Intervention | participant (Number) |
|---|
| Lenalidomide | 70 |
Kaplan Meier Estimate for Duration of Transfusion Independence Response
Duration of response is measured from the first of the consecutive 56 days during which the participant was free of RBC transfusions to the date of the first RBC transfusion after this period. Duration of response was censored at the date of last visit for participants who maintained transfusion independence. (NCT00065156)
Timeframe: up to 2 years
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 97.0 |
Time to Transfusion Independence
"Transfusion independence was defined as the absence of an intravenous infusion of any RBC transfusion during any consecutive rolling 56 days during the treatment period (e.g., Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.), and accompanied by at least a 1 g/dL increase from screening/baseline in hemoglobin. Time to transfusion independence was defined as the day of the first dose of study drug to the first day of the first 56-day RBC transfusion-free period." (NCT00065156)
Timeframe: up to 2 years
| Intervention | weeks (Mean) |
|---|
| Lenalidomide | 6.2 |
Change in Hemoglobin Concentration From Baseline to Maximum Value During Response Period for Responders
The change from baseline in hemoglobin for participants who became RBC-transfusion independent. The maximum hemoglobin value obtained during the response period is used in the calculation of change from baseline. (NCT00065156)
Timeframe: Baseline (Day -54 to Day 0), During study (Day 1 up to 2 years)
| Intervention | g/dL (Mean) |
|---|
| Lenalidomide | 6.1 |
Participants With Complete or Partial Bone Marrow Improvement
Bone marrow aspirates were assessed by a central reviewer. A complete bone marrow improvement required a baseline French-American-British (FAB) classification (see Baseline Characteristics) of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB) or chronic myelomonocytic leukemia (CMML) and a during study assessment of no MDS. A partial bone marrow improvement reflected an improved FAB classification compared to baseline (e.g. RARS to RA) but evidence of MDS continued to exist. (NCT00065156)
Timeframe: up to 2 years
| Intervention | participants (Number) |
|---|
| Complete bone marrow improvement | Partial bone marrow improvement |
|---|
| Lenalidomide | 22 | 15 |
Efficacy of CC-5013 in Myelofibrosis
"Response evaluation, sustained for 2 weeks: Complete Remission (Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow); Partial Hematologic Response/Partial Remission (Increase in neutrophil by 50% + above 10^9/L for neutropenia); Hematologic Improvement (increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts) or No Response.~If nine or < patients respond to therapy (response other than 'No Response'), therapy declared ineffective. However, if 11 or > patients respond to therapy, therapy considered efficacious." (NCT00087672)
Timeframe: 3 - 4 Months for all patients; 24 months for responders
| Intervention | Participants (Number) |
|---|
| Complete Remission | Partial Remission | Hematologic Improvement | No Response |
|---|
| CC-5013 | 7 | 9 | 12 | 9 |
Number of Patients Removed From Study Treatment Due to Toxicities
(NCT00091260)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Revlimid | 31 |
Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response
(NCT00091260)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Revlimid | 26 |
Number of Patients With Hematologic Response With Single-agent CC-5013
"Complete response = Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, less than 5% plasma cells on bone marrow biopsy without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay.~Partial response= For patients with detectable and quantifiable monoclonal marrow plasmacytosis= a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum or urine protein electrophoresis= a reduction in the peak height of 50% or more.~For patients with quantifiable urinary kappa or lambda chain concentration= a 50% reduction in daily light chain excretion in 24 hour urine.~For patients with an elevated serum free light chain assay, a reduction of 50% or more." (NCT00091260)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Revlimid | 5 |
Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab
Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0 (NCT00096044)
Timeframe: Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Oral Lenalidomide | 1 | 0 | 3 | 3 |
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab
Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. (NCT00096044)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Oral Lenalidomide | 100 |
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months
Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. (NCT00096044)
Timeframe: at 6 Months
| Intervention | percentage of participants (Number) |
|---|
| Oral Lenalidomide | 68.9 |
Time to Progression for the Combination Therapy of CC-5013+Rituximab
Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. (NCT00096044)
Timeframe: Every month up to 6 months and every 3 months thereafter up to 5 years
| Intervention | months (Median) |
|---|
| Oral Lenalidomide | 18.7 |
Number of Participants With Adverse Events on Single Agent CC-5013
"Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0~Please refer to the adverse event reporting for more detail." (NCT00096044)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Oral Lenalidomide | 0 | 3 | 7 | 33 | 2 |
Time to Progression for Single Agent CC-5013
Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. (NCT00096044)
Timeframe: 5 years
| Intervention | months (Median) |
|---|
| Oral Lenalidomide | 23.0 |
Proportion of Patients With Objective Response (First Phase, Step 2)
"Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response).~As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only." (NCT00098475)
Timeframe: Assessed every 4 weeks for 16 weeks during Step 2
| Intervention | Proportion of patients (Number) |
|---|
| Arm I (Lenalidomide, Dexamethasone) | 0 |
| Arm II (Lenalidomide, Low-dose Dexamethasone) | 0 |
Proportion of Patients With Objective Response (First Phase, Step 1)
"Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response).~As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only." (NCT00098475)
Timeframe: Assessed every 4 weeks for 16 weeks during Step 1
| Intervention | Proportion of patients (Number) |
|---|
| Arm I (Lenalidomide, Dexamethasone) | 0.79 |
| Arm II (Lenalidomide, Low-dose Dexamethasone) | 0.683 |
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module. (NCT00109005)
Timeframe: 24 months
| Intervention | Participants (Number) |
|---|
| Cohort 1 - 25 mg Lenalidomide (Revlimid) | 8 |
| Cohort 2 - 5 mg Lenalidomide (Revlimid) | 9 |
Change From Baseline in the Brief Pain Inventory (BPI) Total Score at Week 12
Participants completed the Brief Pain Inventory which asks twelve questions that are rated on an eleven-point scale in which 0=most positive outcome and 10=the most negative outcome for a total scale of 0-120. BPI contains questions that concern the level of pain over the last week and the level of pain right now, the extent to which pain interfered with sleep, normal activities, ability to work, relationships, walking etc. Week 12 values are compared to baseline values. Negative change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -4.8 |
| Placebo to Lenalidomide | -3.7 |
"Change From Baseline in Mechanically Evoked (Allodynia) Numeric Rating Scale (NRS) Score at Week 12"
The investigator rated the degree of allodynia on both the CRPS-affected limb on an eleven-point scale where 0=no pain and 10=worst pain imaginable. This outcome compares the baseline values for the CRPS affected-limb to the values at week 12. Negative change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -0.8 |
| Placebo to Lenalidomide | -0.1 |
Change From Baseline in the Evening Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12
Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. The evening pain ratings at baseline and Week 12 are compared. Negative changes indicate improvement in level of pain. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -0.6 |
| Placebo to Lenalidomide | -0.4 |
Change From Baseline in Daily Sleep Assessment Average Score at Week 12
Participants rated how much CRPS pain interfered with their sleep each day in a diary. The Sleep Assessment uses an eleven point scale for four questions. Questions concern ability to fall asleep, ability to stay asleep, how refreshed the participant feels upon waking and how alert the participant is during the day. All use a scale of 0-10, where the higher number is the positive response (e.g. 0=Pain completely interferes with sleep and 10=Pain does not interfere). The mean of all four responses was calculated if at least 3 of the 4 questions had a value. Week 12 values are compared to baseline values. Positive change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 0.7 |
| Placebo to Lenalidomide | 0.7 |
Change From Baseline in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score Using Averaged Morning and Evening Readings at Week 12
Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. Morning and evening scores are averaged. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Week 12 values are compared to baseline values. Negative changes indicate improvement in level of pain. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -0.6 |
| Placebo to Lenalidomide | -0.4 |
Change From Baseline in Activity Level Rating Using a Numeric Rating Scale (NRS) at Week 12
Participants rated how the activity level on a given day compares with their activity level prior to the start of treatment. A seven-point scale is used with -3=much worse and +3=much better. Positive change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 0.1 |
| Placebo to Lenalidomide | 0.2 |
Change From Baseline in Participant Assessment of CRPS Symptoms Total Score at Week 12
Participants rated twelve CRPS symptoms using a four-point rating scale in which 1=the most positive outcome and 4= the most negative outcome for a total scale of 12-48. Week 12 values are compared to baseline values. Negative change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -2.4 |
| Placebo to Lenalidomide | -1.4 |
Percentage of Participants Who Have a >= 30% Reduction (Improvement) in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score From Baseline to the Last Assessment
Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. Responders are participants who completed 12 weeks of treatment and their week 12 PI-NRS score showed at least a 30% improvement from baseline. Participants who did not complete 12 weeks of treatment are considered non-responders. (NCT00109772)
Timeframe: Day 0, Week 12
| Intervention | percentage of participants (Number) |
|---|
| Responders | Non-responders |
|---|
| Lenalidomide | 16.1 | 83.9 |
,| Placebo to Lenalidomide | 16.1 | 83.9 |
Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period
"Counts of study participants who had adverse events (AEs) while treated in either the Double-blind or Extension Periods. The NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 was used by the investigator to grade the severity of the AEs: Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE, Grade 5=Death related to AE.~AEs are also summarized by whether they were serious, related to treatment and whether the AE caused treatment to be altered.~A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event could have jeopardized the patient's safety or required medical or surgical intervention to prevent one of the outcomes listed above." (NCT00109772)
Timeframe: Day 1 up to week 158
| Intervention | participants (Number) |
|---|
| Adverse event (AE) | Serious adverse event (SAE) | AE leading to study drug discontinuation | AE leading to dose reduction or interruption | Treatment-related AE | Treatment-related SAE | Grade 2 or higher AE | Grade 3 or higher AE |
|---|
| Lenalidomide | 83 | 12 | 29 | 10 | 68 | 1 | 63 | 15 |
,| Placebo to Lenalidomide | 85 | 16 | 29 | 8 | 66 | 5 | 68 | 18 |
Participants Who Had a Change to CRPS Pain Medication During the Treatment Period
Participants who had any change in CRPS medication during the double-blind treatment period (up to week 12) are summarized. Changes include additions, discontinuations or dosage change of CRPS medication(s). (NCT00109772)
Timeframe: Day 1 to week 12
| Intervention | participants (Number) |
|---|
| Change to CRPS medication(s) | No change to CRPS medication |
|---|
| Lenalidomide | 11 | 76 |
,| Placebo to Lenalidomide | 7 | 86 |
Patient Global Impression of Change (PGIC) at Week 12
The Patient Global Impression of Change asks the question: Overall, how would you rate your CRPS condition since the start of study drug? Answers are represented on a seven-point scale with -3=much worst and +3=much better. (NCT00109772)
Timeframe: Week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 0.2 |
| Placebo to Lenalidomide | 0.2 |
Difference in Allodynia Rating Between the CRPS-affected Limb and the Normal Limb at Week 12
The investigator rated the degree of allodynia on both the CRPS-affected limb and the normal (or less-affected) limb on an eleven-point scale where 0=no pain and 10=worst pain imaginable. This outcome compares the values for the CRPS affected-limb to the normal limb at week 12. (NCT00109772)
Timeframe: Week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 3.7 |
| Placebo to Lenalidomide | 4.1 |
Change From Baseline in the Profile of Mood States (POMS) at Week 12
Participants completed the Profile of Mood States questionnaire that asks participants to rate how each of 65 words reflected their mood in the past week on a 5-point scale with 0=not at all and 4=extremely for a total scale of 0-260. Week 12 values are compared to baseline values. Negative change values indicate improvement. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -9.6 |
| Placebo to Lenalidomide | -4.5 |
Change From Baseline in the Morning Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12
Participants rated the intensity of pain in the CRPS-affected limb twice each day in a diary. The PI-NRS is an eleven point scale with 0=no pain and 10=worst pain imaginable. The morning pain ratings at baseline and Week 12 are compared. Negative changes indicate improvement in level of pain. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -0.6 |
| Placebo to Lenalidomide | -0.4 |
Change From Baseline in the Maximal Composite Sensory Nerve Conduction Velocity at Week 12
An electrophysiological evaluation using standard electrophysiological and electromyography to measure the speed and extent of nerve conduction. Week 12 values are compared to baseline values for maximal sensory nerve conduct velocity. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | meters/second (Mean) |
|---|
| Lenalidomide | 1.2 |
| Placebo to Lenalidomide | 0.1 |
Change From Baseline in the Maximal Composite Motor Nerve Conduction Velocity at Week 12
An electrophysiological evaluation using standard electrophysiological and electromyography to measure the speed and extent of nerve conduction. Week 12 values are compared to baseline values for maximal motor nerve conduct velocity. (NCT00109772)
Timeframe: Day 0, week 12
| Intervention | meters/second (Mean) |
|---|
| Lenalidomide | 0.3 |
| Placebo to Lenalidomide | 0.1 |
Maximum Tolerated Dose (MTD)
The highest dose tested (Total Marrow Irradiation) in which there is no treatment related mortality and none or only one patient experienced dose limited toxicity (DLT) attributable to the study drug(s), when at least six were fully treated at that dose and fully followed for toxicity. The MTD is one dose level below the lowest dose tested in which 2 or more patients experienced DLT attributable to the treatment or there was a treatment related death. At least 6 patients will be treated at the MTD. (NCT00112827)
Timeframe: 8 weeks from start of treatment, up to 2 years
| Intervention | cGy (Number) |
|---|
| Treatment Arm | 1600 |
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause. (NCT00112827)
Timeframe: From date of treatment until the date of death from any cause, assessed up to 14 years
| Intervention | months (Median) |
|---|
| Treatment Arm | 95.8 |
Number of Subjects With Response
Response defined as complete response or very good partial response. Complete response defined as the absence of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval. Thus all evidence of serum and urinary M-components must disappear on electrophoresis as well as by immunofixation studies. The follow-up bone marrow may not contain more than 5% plasma cells on aspiration or core biopsy and no evidence of increasing anemia. Skeletal X-rays must either show recalcification or no change in osteolytic lesions. Resolution of soft tissue plasmocytomas. Very good partial response defined as reduction of bone marrow or blood findings of multiple myeloma on at least 2 measurements at a minimum of a 6 week interval by greater than or equal to 90%. (NCT00112827)
Timeframe: Evaluated after each course until completion of treatment.
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Cohort 1 (Total TMI Dose: 1000 cGy) | 3 |
| Phase 1 Cohort 2 (Total TMI Dose: 1200 cGy) | 3 |
| Phase 1 Cohort 3 (Total TMI Dose: 1400 cGy) | 2 |
| Phase 1 Cohort 4 & Phase 2 MTD (Total TMI Dose:1600 cGy) | 20 |
| Phase 1 Cohort 5 (Total TMI Dose: 1800 cGy) | 4 |
Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100
"Response was defined according to International Myeloma Working Group criteria (2006)~Complete Response: Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM)~Partial Response: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels~Marginal Response: 25-49% reduction in serum M-component & urine M-component by 50-89% which still exceeds 200mg/24hour~Progressive Disease: Defined in primary outcome measure~Stable Disease: Not meeting any of the criteria above" (NCT00114101)
Timeframe: Day 100
| Intervention | participants (Number) |
|---|
| Complete response | Partial response | Marginal response | Stable disease | Progressive disease | Unknown |
|---|
| Lenalidomide Maintenance | 67 | 115 | 11 | 38 | 0 | 0 |
,| Placebo Maintenance | 79 | 109 | 5 | 32 | 3 | 1 |
Number of Participants With Progression, Death or Diagnosis of Second Primary Malignancy
Patients who develop progression (defined in primary outcome measure), died or develop a new primary malignancy (cancer) will summarized in this outcome. (NCT00114101)
Timeframe: Duration of study (up to 10 years)
| Intervention | participants (Number) |
|---|
| Lenalidomide Maintenance | 92 |
| Placebo Maintenance | 133 |
Overall Survival
Overall Survival was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method. (NCT00114101)
Timeframe: Duration of study (up to 10 years)
| Intervention | months (Median) |
|---|
| Lenalidomide Maintenance | NA |
| Placebo Maintenance | NA |
Time to Progression
"Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method.~Progression was defined per the International Myeloma Working Group definition as one more of the following:~25% increase in serum M-component (absolute increase >= 0.5g/dl)~25% increase in urine M-component (absolute increase >= 200mg/24hour~25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)~25 % increase in bone marrow plasma cell percentage (absolute increase of >=10%)~Definite development of new bone lesion or soft tissue plasmacytomas~Development of hypercalcemia" (NCT00114101)
Timeframe: Duration of study (up to 10years)
| Intervention | months (Median) |
|---|
| Lenalidomide Maintenance | 39 |
| Placebo Maintenance | 21 |
Minor Response Rate
A minor response is defined as having achieved >25% but less than 50% reduction in serum IgM levels. (NCT00142168)
Timeframe: 34.3 months
| Intervention | participants (Number) |
|---|
| Lenalidomide and Rituximab | 4 |
Major Response Rate
Major response rate is the number of participants who achieve at a PR or better. A PR or better will be defined as achieving a >50% reduction in serum IgM levels. (NCT00142168)
Timeframe: 34.3 months
| Intervention | participants (Number) |
|---|
| Lenalidomide and Rituximab | 4 |
Time to Progression
Time to progression is measured as the length in time in months from starting therapy until progression, defined as 25% increase in serum IgM from nadir. (NCT00142168)
Timeframe: 34.3 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Rituximab | 17.1 |
Overall Response
Overall response is the total number of participants who respond to therapy. Patients achieving a complete response (CR) will be defined as having achieved resolution of all symptoms, normalization of their serum IgM levels with complete disappearance of their IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly during any point while in this study and normal bone marrow biopsy. Patients achieving a partial response (PR) and a minor response (MR) will be defined as achieving a > 50% and > 25% reduction in serum IgM levels, respectively, during any point while in this study. Patients with stable disease (SD) will be defined as having < 25% change in serum IgM levels, in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WMduring any point while in this study. (NCT00142168)
Timeframe: 34.3 months
| Intervention | participants (Number) |
|---|
| Lenalidomide and Rituximab | 8 |
Participants' Response Based on Bone Marrow Samples by the International MDS Working Group (IWG 2000) During Double-blind Period
The IWG criteria for bone marrow improvement: a complete remission is bone marrow sampling showing less than 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. A partial remission is ≥ 50% decrease in blasts over pre-treatment. Bone marrow progression is a ≥ 50% increase in blasts that exceed the top range of the pretreatment percentile range: a) <5% blasts b) 5-10% blasts c) 10-20% blasts d) 20-30% blasts. For example, a participant with <5% blasts pretreatment with an on study blast increase of 50% which is now >5% showed bone marrow progression. (NCT00179621)
Timeframe: up to 52 weeks
| Intervention | Participants (Number) |
|---|
| Complete remission | Partial remission | Stable Disease | Progression |
|---|
| Lenalidomide 10 mg | 12 | 1 | 33 | 3 |
,| Lenalidomide 5 mg | 7 | 5 | 35 | 4 |
,| Placebo | 0 | 0 | 37 | 3 |
Participants' Response in Absolute Neutrophil Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period
A major neutrophil response is defined by the International MDS Working Group (IWG) criteria as at least a 100% increase, or an absolute increase of ≥500/mm^3 for participants with absolute neutrophil counts (ANC) of less than 1,500/mm^3 before therapy, whichever is greater. A minor response for such participants is defined as an ANC increase of at least 100%, but absolute increase <500/mm^3. (NCT00179621)
Timeframe: up to week 52
| Intervention | Participants (Number) |
|---|
| Major | Minor | None |
|---|
| Lenalidomide 10 mg | 2 | 1 | 14 |
,| Lenalidomide 5 mg | 3 | 0 | 15 |
,| Placebo | 1 | 0 | 9 |
Participants' Response in Platelet Counts as Defined by the International MDS Working Group (IWG 2000) During Double-blind Period
The International MDS Working Group (IWG) defines a major platelet response for participants with a pre-treatment platelet count of <100,000/mm^3 as an absolute increase of ≥30,000/mm^3 whereas a minor response is defined as a ≥50% increase in platelet count with a net increase greater than 10,000/mm^3 but less than 30,000/mm^3. (NCT00179621)
Timeframe: up to 52 weeks
| Intervention | Participants (Number) |
|---|
| Major | Minor | None |
|---|
| Lenalidomide 10 mg | 1 | 0 | 3 |
,| Lenalidomide 5 mg | 1 | 0 | 5 |
,| Placebo | 0 | 0 | 3 |
Summary of Participants Who Had Adverse Events (AE) During the Double-blind Period
"Counts of study participants who had adverse events (AEs) during the double-blind period by MedDRA System Organ Class (SOC) and preferred term. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.~The National Cancer Institute (NCI)'s Common Terminology Criteria for AEs (CTCAE) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE." (NCT00179621)
Timeframe: up to week 52
| Intervention | participants (Number) |
|---|
| At least one AE | At least one AE related to study drug | At least one NCI CTCAE grade 3-4 AE | At least one related NCI CTCAE grade 3-4 AE | At least one serious AE | At least one serious AE related to study drug | An AE leading to discontinuation of study drug | An AE leading to dose reduction or interruption | Deaths within 30 days of last dose of study drug |
|---|
| Lenalidomide 10 mg | 69 | 66 | 65 | 61 | 32 | 13 | 6 | 51 | 4 |
,| Lenalidomide 5 mg | 69 | 68 | 62 | 61 | 31 | 17 | 12 | 44 | 2 |
,| Placebo | 64 | 34 | 29 | 13 | 14 | 1 | 3 | 5 | 4 |
Participants Who Progressed to Acute Myeloid Leukemia (AML) During the Study
Number of participants who progressed to acute myeloid leukemia during the study, summarized at three different timepoints: first 16 weeks of the double-blind study, week 52 of the double-blind study, and up to 36 months which includes the double-blind and open-label periods of the study. The counts are cumulative by timeframe. (NCT00179621)
Timeframe: up to 3 years
| Intervention | Participants (Number) |
|---|
| Double-Blind (first 16 weeks) | Double-Blind (52 weeks) | Double-Blind + Open-Label |
|---|
| Lenalidomide 10 mg | 0 | 2 | 15 |
,| Lenalidomide 5 mg | 2 | 7 | 16 |
,| Placebo | 2 | 4 | 21 |
Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Week 12
"The Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire (Yellen, 1997) was used to assess health-related quality of life (HRQoL).~In addition to general HRQoL, the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning. The overall score range for the FACT-An is 0-188. Higher scores indicate better HRQoL." (NCT00179621)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -2.5 |
| Lenalidomide 5 mg | 5.9 |
| Lenalidomide 10 mg | 5.8 |
Change From Baseline in the Trial Outcome Index-Anemia (TOI-An) Endpoints at Week 12
The Trial Outcome Index-Anemia (TOI-An) composed of the physical and functional subscales of the FACT-G along with the Anemia subscale was used to assess health-related quality of life (HRQoL). The overall score range for the TOI-An is 0-136. Higher scores indicate better HRQoL. (NCT00179621)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -1.1 |
| Lenalidomide 5 mg | 5.6 |
| Lenalidomide 10 mg | 4.9 |
Change From Baseline in the Trial Outcome Index-Fatigue (TOI-F) Endpoints at Week 12
The Trial Outcome Index-Fatigue(TOI-F) composed of the physical and functional subscales of the FACT-G along with the fatigue items from the Anemia subscale was used to assess health-related quality of life (HRQoL). The overall score range for the TOI-F is 0-108. Higher scores indicate better HRQoL. (NCT00179621)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -0.8 |
| Lenalidomide 5 mg | 4.8 |
| Lenalidomide 10 mg | 3.9 |
Duration of Red Blood Cell (RBC) Transfusion Independence for Participants Who Became RBC Transfusion Independent for at Least 182 Days
Mean number of weeks that participants who achieved RBC transfusion independence for at least 182 days were able to maintain RBC transfusion independence. Both double-blind and open-label periods are included. (NCT00179621)
Timeframe: up to 3 years
| Intervention | Weeks (Mean) |
|---|
| Placebo | 61.4 |
| Lenalidomide 5 mg | 107.7 |
| Lenalidomide 10 mg | 108.6 |
Kaplan Meier Estimates of Overall Survival by Randomized Group
Kaplan Meier estimate for median length of survival for study participants as they were randomized at the start of the study. (NCT00179621)
Timeframe: up to 3 years
| Intervention | Months (Median) |
|---|
| Placebo | 42.4 |
| Lenalidomide 5 mg | NA |
| Lenalidomide 10 mg | 44.5 |
Maximum Change From Baseline in Hemoglobin During the Double-blind Period for Participants Who Became Red Blood Cell (RBC) Transfusion Independent for at Least 182 Days
For participants who became RBC transfusion independent for at least 182 days during the double-blind study period, the mean maximum change from baseline in hemoglobin is summarized. (NCT00179621)
Timeframe: Baseline, up to 52 weeks
| Intervention | g/dL (Mean) |
|---|
| Placebo | 2.0 |
| Lenalidomide 5 mg | 5.5 |
| Lenalidomide 10 mg | 6.0 |
Participant Count of Deaths During Double-blind and Open-label by Randomized Group
Count of participant deaths throughout the entire study and reported by the original treatment assignment. (NCT00179621)
Timeframe: up to 3 years
| Intervention | Participants (Number) |
|---|
| Placebo | 35 |
| Lenalidomide 5 mg | 32 |
| Lenalidomide 10 mg | 34 |
Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for >= 26 Weeks (182 Days)
The count of study participants who had no RBC transfusions for 26 consecutive weeks or more during the double-blind period. (NCT00179621)
Timeframe: Up to 52 weeks
| Intervention | Participants (Number) |
|---|
| Placebo | 3 |
| Lenalidomide 5 mg | 20 |
| Lenalidomide 10 mg | 23 |
Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for 56 Days
Count of study participants who had no RBC transfusions during any 56 or more consecutive study days during the double-blind period. (NCT00179621)
Timeframe: Up to 52 weeks
| Intervention | Participants (Number) |
|---|
| Placebo | 4 |
| Lenalidomide 5 mg | 24 |
| Lenalidomide 10 mg | 25 |
Participants Showing Cytogenetic Response by the International MDS Working Group (IWG 2000) During Double-blind Period as Evaluated by Central Review
The IWG criteria for evaluating cytogenetic response require a minimum of 20 baseline and post-baseline analyzable metaphases using conventional cytogenetic techniques. A major cytogenetic response is defined as no detectable cytogenetic abnormality if preexisting abnormality was present whereas a minor response requires ≥50% reduction in abnormal metaphases. Progression could be concluded based on as few as 3 metaphases if there were additional abnormalities. The best response is represented. (NCT00179621)
Timeframe: up to 52 weeks
| Intervention | Participants (Number) |
|---|
| Major response | Minor response | Cytogenetic progression | Not evaluable/data not available |
|---|
| Lenalidomide 10 mg | 10 | 7 | 8 | 1 |
,| Lenalidomide 5 mg | 5 | 3 | 10 | 10 |
,| Placebo | 0 | 0 | 5 | 10 |
Overall Incidence of Adverse Events
Data from all subjects who received any study drug were included in the analysis. Adverse events were classified using the Medical Dictionary for Regulatory Activities (MedDRA) classification system. A subject having the same event more than once was counted only once. Adverse events were summarized by worst NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) VERSION 3.0 grade. Incidence was defined as the number of subjects who experienced an adverse event within their period of participation in this study. (NCT00179647)
Timeframe: Median time-on-study=18.3 weeks
| Intervention | Participants (Number) |
|---|
| Lenalidomide | 1877 |
Duration of Response
The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate. (NCT00179660)
Timeframe: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
| Intervention | months (Median) |
|---|
| Lenalidomide | 10.2 |
Duration of Tumor Control
The duration of tumor control was calculated as the time from the first response assessment demonstrating at least stable disease to the first documentation of progressive disease or death due to NHL. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate. (NCT00179660)
Timeframe: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
| Intervention | months (Median) |
|---|
| Lenalidomide | 6.0 |
Percentage of Participants With Response
"Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator.~CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.~Cru: Criteria for CR above but with 1 or more of the following:~A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD)~Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).~PR: 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD." (NCT00179660)
Timeframe: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 34.7 |
Percentage of Participants With Tumor Control
"Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator.~SD was defined as a response less than a PR (see above) but not Progressive Disease (PD).~PD was defined as~≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders.~Appearance of any new lesion during or at the end of therapy." (NCT00179660)
Timeframe: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 59.2 |
Progression-free Survival
"Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first.~Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment." (NCT00179660)
Timeframe: From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.
| Intervention | months (Median) |
|---|
| Lenalidomide | 3.6 |
Number of Participants With Adverse Events (AEs)
"The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event.~The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale:~Grade 1 = Mild~Grade 2 = Moderate~Grade 3 = Severe~Grade 4 = Life threatening~Grade 5 = Death~A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event." (NCT00179660)
Timeframe: From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 15.2 months.
| Intervention | participants (Number) |
|---|
| Any adverse event | Adverse event related to study drug | Grade 3-5 adverse event | Grade 3-5 adverse event related to study drug | Serious adverse event | Serious adverse event related to study drug | AE leading to discontinuation of study drug | Related AE leading to study drug discontinuation | AE leading to dose reduction or interruption |
|---|
| Lenalidomide | 49 | 42 | 36 | 27 | 21 | 6 | 9 | 4 | 28 |
Percentage of Participants With Response
"Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.~Cru: Criteria for CR above but with 1 or more of the following:~A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD)~Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).~PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD." (NCT00179673)
Timeframe: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 23.3 |
Percentage of Participants With Tumor Control
"Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator.~SD was defined as a response less than a PR (see above) but not Progressive Disease (PD).~PD was defined as~≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders.~Appearance of any new lesion during or at the end of therapy." (NCT00179673)
Timeframe: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 60.5 |
Progression Free Survival (PFS)
Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment. (NCT00179673)
Timeframe: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 4.4 |
Number of Participants With Adverse Events (AEs)
"The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event.~The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale:~Grade 1 = Mild~Grade 2 = Moderate~Grade 3 = Severe~Grade 4 = Life threatening~Grade 5 = Death~A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event." (NCT00179673)
Timeframe: From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months.
| Intervention | participants (Number) |
|---|
| At least one Adverse Event (AE) | ≥ 1 AE related to study drug | Grade (GR) 3-5 AE | Grade 3-5 AE related to study drug | Serious adverse event (SAE) | SAE related to study drug | AE leading to discontinuation of study drug | Related AE leading to study drug discontinuation | AE leading to dose reduction or interruption |
|---|
| Lenalidomide | 42 | 37 | 27 | 24 | 18 | 10 | 9 | 5 | 27 |
The Duration of Response
The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate. (NCT00179673)
Timeframe: From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months
| Intervention | months (Median) |
|---|
| Lenalidomide | NA |
Overall Response Rate
"Response was evaluated for Anemia and Spleen:~Major anemia response: hemoglobin increase to within normal limits in the absence of transfusion. Minor anemia response: hemoglobin improvement of at least 2 grams per deciliter independent of transfusion support, or achievement of transfusion independence in transfusion-dependent patients. Major spleen response: normalization of spleen size to the range of 12-14 centimeters by ultrasound. Minor spleen response: a 50% or more decrease in excess spleen size by ultrasound. Complete remission (CR): complete resolution of disease-related symptoms, splenomegaly, normalization of peripheral blood count, white cell differential and smear, and normalization of bone marrow histology. Partial remission (PR): a major or minor response in anemia or splenomegaly. Overall Response (OR)=CR + PR, assessed among eligible, treated patients." (NCT00227591)
Timeframe: Assessed at the end of cycle 3
| Intervention | Proportion of participants (Number) |
|---|
| Lenalidomide | 0.26 |
Time to Progression
Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method. (NCT00238238)
Timeframe: Up to 10 years
| Intervention | years (Median) |
|---|
| Arm II - Lenalidomide | 1.1 |
| Arm III - Lenalidomide and Rituximab | 2 |
Overall Response Rate
Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease. (NCT00238238)
Timeframe: Duration of treatment (12 cycles)
| Intervention | percentage of participants (Number) |
|---|
| Arm II - Lenalidomide | 53.3 |
| Arm III - Lenalidomide and Rituximab | 76.1 |
Number of Patients in Overall Response Categories
Overall Response defined as participant had either complete response (CR) or partial response (PR) assessed after three cycles, at six months and yearly thereafter using the NCI-Working Group Criteria: Complete Response, Complete Response with Nodules, Partial Response, or No Response. (NCT00267059)
Timeframe: Evaluated after three 28-day cycles of lenalidomide.
| Intervention | Participants (Number) |
|---|
| Complete Response | Complete Response With Nodules | Partial Response | No Response |
|---|
| Lenalidomide | 3 | 1 | 10 | 30 |
Response Rate
Percentage of patients who responded to treatment (either stable disease or complete response) based on total tumor volume measurements from CT scans. (NCT00287287)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide (Revlimid) | 17 |
Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab
MTD is defined as the highest dose level in which 1 or fewer participants experienced a dose limiting toxicity (DLT) in 6 participants treated. DLT is any grade III or IV toxicity during the first 28 days (first cycle) of therapy. (NCT00294632)
Timeframe: 28 days of cycle 1
| Intervention | mg (Number) |
|---|
| Phase I: Lenalidomide + Rituximab | 20 |
Objective Response Rate of Participants Treated With Lenalidomide 20 mg: Overall Response as % of Participants With Complete or Partial Response
Objective response rate defined as percentage of participants with complete or partial response after 2 cycles of therapy maintained for one month. Objective response monitored using Simon's optimal 2-stage design. (NCT00294632)
Timeframe: 56 days
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide + Rituximab | 57 |
Plasma Concentration of Revilimid at Steady State
Mean plasma concentration (ng/mL) of Revilimid at steady state (Day 21 of second treatment cycle) (NCT00348595)
Timeframe: Day 21 of second treatment cycle
| Intervention | ng/mL (Mean) |
|---|
| Revlimid 5mg/Day | 12.67 |
| Revlimid 25mg/Day | 65.14 |
Safety, Feasibility and Tolerance of Revlimid as Assessed by Number of Participants Experiencing Grade 3 and 4 Adverse Events.
Number of participants experiencing Grade 3 and 4 adverse events as defined by the National Cancer Institute Common Toxicity Criteria version 3.0 (NCT00348595)
Timeframe: 6 months post-intervention
| Intervention | Participants (Count of Participants) |
|---|
| Revlimid 5mg/Day | 3 |
| Revlimid 25mg/Day | 10 |
Change in of PSA Slope
Mean change in PSA slope from baseline to 6 months. PSA slope was calculated using the regression of log PSA over 6 months in each patient. A negative mean change in PSA slope reflects a better outcome. (NCT00348595)
Timeframe: Change from baseline to 6 months post-intervention
| Intervention | log PSA (Mean) |
|---|
| Revlimid 5mg/Day | -0.033 |
| Revlimid 25mg/Day | -0.172 |
Number of Participants With Prostate-specific Antigen (PSA) Progression
Number of participants with greater than or equal to 25% increase in PSA at 6 months (NCT00348595)
Timeframe: 6 months post-intervention
| Intervention | Participants (Count of Participants) |
|---|
| Revlimid 5mg/Day | 7 |
| Revlimid 25mg/Day | 5 |
Overall Survival Among Patients With Complete Response
Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study (NCT00352001)
Timeframe: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Azacitidine | 37 |
PHASE I: Maximum Tolerated Dose of Azacitidine
"Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard 3+3 design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here." (NCT00352001)
Timeframe: After 1 courses (1 months)
| Intervention | mg/m2 subcutaneously for 5 days (Number) |
|---|
| Lenalidomide and Azacitidine | 75 |
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
"For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement.~Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones.~Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality.~Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L" (NCT00352001)
Timeframe: After 4 courses (4 months)
| Intervention | participants (Number) |
|---|
| Lenalidomide and Azacitidine | 26 |
Time to Relapse After Achieving Complete Response
(NCT00352001)
Timeframe: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Azacitidine | 17 |
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
"For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement)~Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones.~Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality.~Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L" (NCT00352001)
Timeframe: After 7 courses (months)
| Intervention | participants (Number) |
|---|
| Lenalidomide and Azacitidine | 26 |
PHASE I: Maximum Tolerated Dose of Lenalidomide
"Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard 3+3 design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here." (NCT00352001)
Timeframe: After 1 courses (1 months)
| Intervention | mg orally for 21 days (Number) |
|---|
| Lenalidomide and Azacitidine | 10 |
Total Response
Morphologic complete remission (CR): ANC >=1,000/mcl, platelet count >=100,000/mcl, <5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be <1,000/mcl and/or platelet count <100,000/mcl. Partial remission (PR): ANC >1,000/mcl, platelet count >100,000/mcl, and at least 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods. (NCT00352365)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Therapy | 14 |
Cytogenetic Abnormalities
Number of baseline cytogenetic abnormalities by responders (CR, CRi, and PR) and nonresponders. (NCT00352365)
Timeframe: Up to 5 years
| Intervention | Number of abnormalities (Median) |
|---|
| Responders | 8 |
| Nonresponders | 8 |
Complete Response
Morphologic complete remission (CR): ANC >=1,000/mcl, platelet count >=100,000/mcl, <5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be <1,000/mcl and/or platelet count <100,000/mcl. (NCT00352365)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Therapy | 11 |
Number of Patients With Objective Response (Complete and Partial Response + Hematological Improvement)
Time to response defined as the time from start of therapy until the response criteria are fulfilled. Response duration defined as the time from response until relapse (progressive disease) or death. (NCT00352794)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide + Prednisone | 14 |
Number of Participants With a Response (Complete Remissions (CR), Complete Remissions With Incomplete Platelet Recovery [CRp] and Partial Responses)
Response for Acute Myeloid Leukemia (AML) according to 2003 International Working Group (IWG) criteria: CR required absolute neutrophil count (ANC) >1 * 10^9/L, platelet count ≥100 * 10^9/L, < 5% of blast cells in bone marrow. CRp: as above except platelet count <100 * 10^9/L. Partial remission: as CR except for presence of 5-25% marrow blasts and with a decrease of marrow blast at least 50%. Response for Myelodysplastic Syndrome (MDS) was defined based on the 2006 IWG criteria. All participants with MDS who achieved hematological CR, Partial Response (PR), marrow CR, and hematological improvement considered responders. (NCT00360672)
Timeframe: Following three 28-day cycles evaluated for response
| Intervention | participants (Number) |
|---|
| Complete Remission | Complete Remission Incomplete Platelet Recovery | Partial Remission |
|---|
| Revlimid | 1 | 1 | 0 |
Objective Response Rate of the Drug Combination in This Patient Populations.
Overall Response (OR) was defined as partial response (PR) or better. Response was assessed according to European Group for Blood and Marrow Transplant criteria, modified to include nCR and VGPR, from the International Uniform Response Criteria. (NCT00378105)
Timeframe: Full response assessment was conducted at the end of cycle 8 (average of168 days) and after cycle 4 (84 days) for patients proceeding to transplant.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1 Population | 100 |
| Phase II Population | 100 |
| Total | 100 |
Estimated 18-month Overall Survival Rate
Overall survival was measured from treatment initiation to death, censored at the date patients were last known to be alive for those who had not died. (NCT00378105)
Timeframe: Survival rate at 18 months
| Intervention | Percentage of participants (Number) |
|---|
| All Patients | 97 |
Percentage of Patients Who Remained in Response for More Than 18 Months
Duration of response was measured from first response to progression or death, censored at the date patients were last known to be alive and disease free for patients who had not progressed or died. (NCT00378105)
Timeframe: Response rate at 18 months
| Intervention | Percentage of participants (Number) |
|---|
| All Patients | 68 |
Estimated 18-month Progression Free Survival (PFS) Rate
"PD from European Bone Marrow Transplant (EBMT) Response Criteria Required one or more:~>25% increased in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation, or >25% increased in 24-hour urinary light chain excretion (must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation), or >25% increased in plasma cells in a bone marrow aspirate or biopsy (must also be an absolute increase of at least 10%) Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas.~Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture).~Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).~PFS was measured from treatment initiation to progression or death, censored at the date patients were last known to be alive and disease free" (NCT00378105)
Timeframe: PFS rate at 18 months
| Intervention | Percentage of participants (Number) |
|---|
| All Patients | 75 |
Overall Survival
defined as time from treatment initiation to death, or last known to be alive for those who had not died (NCT00378209)
Timeframe: assesed at a median follow-up of 44 months
| Intervention | month (Median) |
|---|
| Lenalidomide, Dexamethasone, Bortezomib Combination | 30 |
The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months
"Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG).~Progressive disease (PD) required one or more of the following:~>25% increased in serum monoclonal paraprotein (must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation) >25% increased in 24-hour urinary light chain excretion (must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation) >25% increased in plasma cells in a bone marrow aspirate or on trephine biopsy (must also be an absolute increase of at least 10%) Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas.~Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture).~Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause)." (NCT00378209)
Timeframe: 6 months after therapy
| Intervention | percentage of treated patients (Number) |
|---|
| Lenalidomide, Dexamethasone, Bortezomib Combination | 75 |
Duration of Response
Duration of response will be measured as the time from initiation of a response to first documentation of disease progression or death, or date last known progression-free and alive for those who have not progressed or died. (NCT00378209)
Timeframe: Assessed at a median follow-up of 44 months
| Intervention | months (Median) |
|---|
| Lenalidomide, Dexamethasone, Bortezomib Combination | 8.7 |
Objective Response Rate
"Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG).~Objective response was defined by the achievement of at least Partial Response (PR) or better (CR-complete response, nCR-near complete response, and VGPR-very good partial response)." (NCT00378209)
Timeframe: Assessed every cycle for up to 8 cycles and best response was reported
| Intervention | percentage of treated patients (Number) |
|---|
| Lenalidomide, Dexamethasone, Bortezomib Combination | 64 |
Progression Free Survival
Progression-free survival is defined as the time from registration to the disease progression or death from any cause, censored at date last known progression-free for those who have not progressed or died. (NCT00378209)
Timeframe: aassesed at a median follow-up of 44 months
| Intervention | months (Median) |
|---|
| Lenalidomide, Dexamethasone, Bortezomib Combination | 9.5 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=114,124,128) | Cycle 7 - approximately Month 7 (n=96,111,112) | Cycle 10 - approximately Month 10 (n=86,93,97) | Cycle 13 - approximately Month 13 (n=73,73,81) | Cycle 16 - approximately Month 16 (n=63,51,62) |
|---|
| MPp+p | -4.9 | -2.7 | -1.7 | -3.3 | -2.2 |
,| MPR+p | 4.8 | 0.6 | -1.1 | -2.7 | -5.2 |
,| MPR+R | -1.8 | -3.5 | -5.0 | -5.0 | -1.6 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhoea Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=115,125,124) | Cycle 7 - approximately Month 7 (n=98,109,112) | Cycle 10 - approximately Month 10 (n=87,92,95) | Cycle 13 - approximately Month 13 (n=73,73,80) | Cycle 16 - approximately Month 16 (n=63,52,61) |
|---|
| MPp+p | 3.2 | 0.9 | -0.0 | 0.8 | 0.5 |
,| MPR+p | 1.9 | -1.2 | 1.4 | -1.4 | 1.3 |
,| MPR+R | 2.3 | 3.4 | 1.1 | 5.5 | 10.6 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=117,126,126) | Cycle 7 - approximately Month 7 (n=100,110,110) | Cycle 10 - approximately Month 10 (n=86,93,96) | Cycle 13 - approximately Month 13 (n=73,73,81) | Cycle 16 - approximately Month 16 (n=62,53,62) |
|---|
| MPp+p | -0.0 | 2.1 | 3.8 | -0.0 | 1.6 |
,| MPR+p | -6.4 | -8.5 | -4.3 | -2.3 | -6.3 |
,| MPR+R | -2.6 | -1.7 | -4.3 | -5.0 | -3.2 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=115,125,128) | Cycle 7 - approximately Month 7 (n=98,111,112) | Cycle 10 - approximately Month 10 (n=86,92,97) | Cycle 13 - approximately Month 13 (n=73,73,83) | Cycle 16 - approximately Month 16 (n=63,52,63) |
|---|
| MPp+p | 6.8 | 5.0 | 4.7 | 6.6 | 6.9 |
,| MPR+p | 2.7 | 4.2 | 1.6 | 1.1 | -0.2 |
,| MPR+R | 4.8 | 8.8 | 9.0 | 8.2 | 9.9 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Congitive Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=115,125,128) | Cycle 7 - approximately Month 7 (n=98,111,113) | Cycle 10 - approximately Month 10 (n=87,92,97) | Cycle 13 - approximately Month 13 (n=73,73,83) | Cycle 16 - approximately Month 16 (n=63,52,63) |
|---|
| MPp+p | 1.3 | 0.7 | -2.7 | -1.4 | -4.0 |
,| MPR+p | -2.0 | 0.1 | -4.4 | -3.0 | -3.5 |
,| MPR+R | 0.3 | 2.9 | 1.0 | -0.0 | 0.3 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=120,127,129) | Cycle 7 - approximately Month 7 (n=100,112,110) | Cycle 10 - approximately Month 10 (n=87,95,95) | Cycle 13 - approximately Month 13 (n=74,74,82) | Cycle 16 - approximately Month 16 (n=64,53,62) |
|---|
| MPp+p | -5.1 | -5.7 | -6.9 | -7.5 | -4.1 |
,| MPR+p | -5.5 | -9.5 | -7.5 | -10.7 | -9.7 |
,| MPR+R | -3.0 | -7.6 | -7.5 | -7.1 | -10.0 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Difficulties Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=111,123,125) | Cycle 7 - approximately Month 7 (n=94,111,112) | Cycle 10 - approximately Month 10 (n=84,92,97) | Cycle 13 - approximately Month 13 (n=70,72,83) | Cycle 16 - approximately Month 16 (n=61,52,63) |
|---|
| MPp+p | -2.9 | -2.1 | -1.7 | -4.0 | -5.3 |
,| MPR+p | -1.1 | -0.6 | 0.7 | -0.5 | -0.6 |
,| MPR+R | 2.4 | 2.1 | 6.0 | 4.8 | 1.6 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=115,125,127) | Cycle 7 - approximately Month 7 (n=98,111,112) | Cycle 10 - approximately Month 10 (n=87,92,97) | Cycle 13 - approximately Month 13 (n=72,73,83) | Cycle 16 - approximately Month 16 (n=63,52,63) |
|---|
| MPp+p | 6.0 | 6.1 | 4.1 | 6.2 | 9.8 |
,| MPR+p | 0.3 | 4.4 | 4.5 | 7.5 | 6.1 |
,| MPR+R | 5.1 | 8.3 | 10.9 | 11.8 | 13.2 |
Summary of Participants With Treatment-Emergent Adverse Events (TEAE) During the Double-Blind Treatment Period
Data as of 11 May 2010 cutoff. Participant counts in different categories of TEAEs during the double-blind treatment period. A TEAE is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. Dose reduction includes reduction with or without interruption. (NCT00405756)
Timeframe: Up to 169 weeks (Double-blind therapy period plus 4 weeks)
| Intervention | participants (Number) |
|---|
| >=1 adverse event (AE) | >=1 CTCAE grade 3-4 AE | >=1 CTCAE grade 5 AE | >=1 serious AE (SAE) | >=1 AE related to Lenaldomide/Placebo | >=1 AE related to Melphalan | >=1AE related to Prednisone | >=1 Grade 3-4 AE related to Lenaldomide/Placebo | >=1 Grade 3-4 AE related to Melphalan | >=1 Grade 3-4 AE related to Prednisone | >=1 Grade 5 AE related to Lenalidomide/Placebo | >=1 Grade 5 AE related to Melphalan | >=1 Grade 5 AE related to Prednisone | >=1 SAE related to Lenalidomide/Placebo | >=1 SAE related to Melphalan | >=1 SAE related to Prednisone | >=1 AE leading to Lenalidomide/Placebo withdrawal | >=1 AE leading to Melphalan withdrawal | >=1 AE leading to Prednisone withdrawal | >=1 AE leading to Lenalidomide/Plac dose reduction | >=1 AE leading to Melphalan dose reduction | >=1 AE leading to Prednisone dose reduction | >=1 AE leading to Lenalidomide/Plac dose interrupt | >=1 AE leading to Melphalan dose interruption | >=1 AE leading to Prednisone dose interruption |
|---|
| MPp+p | 153 | 107 | 7 | 56 | 131 | 126 | 93 | 68 | 62 | 22 | 2 | 3 | 1 | 11 | 11 | 5 | 14 | 10 | 10 | 26 | 21 | 5 | 51 | 0 | 15 |
,| MPR+p | 151 | 129 | 6 | 62 | 145 | 134 | 94 | 117 | 110 | 29 | 2 | 1 | 1 | 32 | 24 | 16 | 24 | 19 | 19 | 70 | 58 | 7 | 82 | 1 | 39 |
,| MPR+R | 150 | 137 | 7 | 66 | 148 | 140 | 87 | 128 | 118 | 32 | 3 | 3 | 1 | 38 | 27 | 19 | 26 | 20 | 20 | 71 | 47 | 15 | 92 | 5 | 28 |
Number of Participants in Disease Response Categories Representing Their Best Response During the Double-blind Treatment Period
Data as of 11 May 2010 cutoff. Best response was determined by the Central Assessment Committee (CAC) based on the European Group for Blood and Marrow Transplantation (EBMT) criteria: Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of bone lesions, plus other factors); Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others; Stable Disease (SD)- not PR or PD; Progressive Disease (PD)- reappearance of monoclonal paraprotein, bone lesions, other; Not Evaluable (NE). (NCT00405756)
Timeframe: Up to 165 weeks
| Intervention | participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Response not evaluable (NE) |
|---|
| MPp+p | 5 | 72 | 70 | 0 | 7 |
,| MPR+p | 5 | 99 | 40 | 2 | 7 |
,| MPR+R | 15 | 102 | 28 | 0 | 7 |
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Side Effects of Treatment Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=113,120,125) | Cycle 7 - approximately Month 7 (n=95,108,111) | Cycle 10 - approximately Month 10 (n=85,89,94) | Cycle 13 - approximately Month 13 (n=72,72,81) | Cycle 16 - approximately Month 16 (n=62,50,61) |
|---|
| MPp+p | 0.6 | 1.8 | 0.3 | 0.3 | -0.9 |
,| MPR+p | 0.1 | -1.7 | 0.0 | -1.0 | -2.9 |
,| MPR+R | 1.3 | 0.4 | -1.6 | -3.8 | -2.1 |
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Future Perspective Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=112,121,124) | Cycle 7 - approximately Month 7 (n=93,108,112) | Cycle 10 - approximately Month 10 (n=83,88,97) | Cycle 13 - approximately Month 13 (n=71,73,81) | Cycle 16 - approximately Month 16 (n=62,52,62) |
|---|
| MPp+p | 7.6 | 9.8 | 14.5 | 11.9 | 14.4 |
,| MPR+p | 4.3 | 7.7 | 6.6 | 6.3 | 7.7 |
,| MPR+R | 4.7 | 14.6 | 17.3 | 17.3 | 18.5 |
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) In Body Image Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=110,117,119) | Cycle 7 - approximately Month 7 (n=88,104,108) | Cycle 10 - approximately Month 10 (n=79,83,94) | Cycle 13 - approximately Month 13 (n=68,72,79) | Cycle 16 - approximately Month 16 (n=59,52,61) |
|---|
| MPp+p | 4.5 | 5.2 | 3.9 | 5.1 | 2.7 |
,| MPR+p | -0.3 | 2.6 | -4.0 | -0.5 | 6.4 |
,| MPR+R | 2.1 | 3.8 | 7.6 | 1.0 | 3.4 |
Kaplan Meier Estimates for Duration of Response as Determined by the Central Adjudication Committee (CAC)
"Data as of 11 May 2010 cutoff. Duration of myeloma response was defined as the time from the initial response date to the earlier of progressive disease (PD) as determined by the CAC or death on study. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.~PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia." (NCT00405756)
Timeframe: Up to 149 weeks
| Intervention | weeks (Median) |
|---|
| MPR+R | 121.6 |
| MPR+p | 56.1 |
| MPp+p | 55.4 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=119,127,130) | Cycle 7 - approximately Month 7 (n=99,112,113) | Cycle 10 - approximately Month 10 (n=86,95,95) | Cycle 13 - approximately Month 13 (n=74,74,82) | Cycle 16 - approximately Month 16 (n=64,53,63) |
|---|
| MPp+p | 7.4 | 6.9 | 5.6 | 5.7 | 7.1 |
,| MPR+p | 3.0 | 8.0 | 7.5 | 11.7 | 8.5 |
,| MPR+R | 1.8 | 5.7 | 9.3 | 9.7 | 12.2 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=120,127,130) | Cycle 7 - approximately Month 7 (n=100,112,112) | Cycle 10 - approximately Month 10 (n=88,95,96) | Cycle 13 - approximately Month 13 (n=75,74,83) | Cycle 16 - approximately Month 16 (n=64,53,63) |
|---|
| MPp+p | 4.5 | 2.7 | 5.1 | 3.3 | 1.1 |
,| MPR+p | 3.3 | 8.1 | 8.5 | 9.7 | 7.6 |
,| MPR+R | 1.9 | 8.2 | 8.9 | 8.6 | 10.0 |
Change From Baseline to Cycles 4, 7, 10, 13, 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=113,121,127) | Cycle 7 - approximately Month 7 (n=96,109,112) | Cycle 10 - approximately Month 10 (n=85,91,95) | Cycle 13 - approximately Month 13 (n=72,73,82) | Cycle 16 - approximately Month 16 (n=62,51,62) |
|---|
| MPp+p | -5.4 | -6.0 | -5.4 | -6.3 | -3.3 |
,| MPR+p | -8.7 | -9.7 | -7.1 | -8.8 | -5.9 |
,| MPR+R | -8.9 | -9.0 | -7.9 | -7.2 | -10.5 |
Kaplan Meier Estimates of Progression-free Survival (PFS) From Start of Maintenance Therapy Period Based on the Response Assessment by the Central Adjudication Committee (CAC)
"Data as of 11 May 2010 cutoff. PFS calculated from the start of the Maintenance period to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause.~PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.~PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia." (NCT00405756)
Timeframe: Approximately week 37 (start of cycle 10) to week 165
| Intervention | weeks (Median) |
|---|
| MPR+R | 112.0 |
| MPR+p | 32.3 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=120,127,129) | Cycle 7 - approximately Month 7 (n=100,112,113) | Cycle 10 - approximately Month 10 (n=88,95,97) | Cycle 13 - approximately Month 13 (n=74,74,83) | Cycle 16 - approximately Month 16 (n=64,53,63) |
|---|
| MPp+p | -13.4 | -11.5 | -9.8 | -12.1 | -12.2 |
,| MPR+p | -13.8 | -16.5 | -15.6 | -14.9 | -11.0 |
,| MPR+R | -14.4 | -17.8 | -17.2 | -13.7 | -20.3 |
Kaplan Meier Estimates for Time to Next Antimyeloma Therapy
Data as of 11 May 2010 cutoff. Time to the next antimyeloma therapy was defined as time from randomization to the start of another non-protocol antimyeloma therapy. Participants who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy. (NCT00405756)
Timeframe: Up to 168 weeks
| Intervention | weeks (Median) |
|---|
| MPR+R | 128.9 |
| MPR+p | 66.1 |
| MPp+p | 66.3 |
Kaplan Meier Estimates of Overall Survival (OS)
Data as of 11 May 2010 cutoff. Overall survival (OS) was defined as the time between randomization and death. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who were lost to follow-up prior to the end of the trial, or who were withdrawn from the trial, were censored at the time of last contact. Participants who were still being treated were censored at the last available date available, or clinical cut-off date, if it was earlier. (NCT00405756)
Timeframe: up to 177 weeks
| Intervention | weeks (Median) |
|---|
| MPR+R | NA |
| MPR+p | NA |
| MPp+p | NA |
Kaplan Meier Estimates of Time to Progression (TTP) Based on the Response Assessment by the Central Adjudication Committee (CAC)
"Data as of 11 May 2010 cutoff. TTP was the time between randomization and disease progression as determined by the CAC. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.~PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia." (NCT00405756)
Timeframe: up to 165 weeks
| Intervention | weeks (Median) |
|---|
| MPR+R | 148.1 |
| MPR+p | 62.7 |
| MPp+p | 61.3 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
Data as of 11 May 2010 cutoff. EORTC QLC-C30 is a 30-item questionnaire to assess the quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); two used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=114,121,125) | Cycle 7 - approximately Month 7 (n=96,108,110) | Cycle 10 - approximately Month 10 (n=84,86,96) | Cycle 13 - approximately Month 13 (n=70,70,82) | Cycle 16 - approximately Month 16 (n=61,50,62) |
|---|
| MPp+p | 6.1 | 4.2 | 6.2 | 5.4 | 8.1 |
,| MPR+p | 5.6 | 8.1 | 8.8 | 8.8 | 7.2 |
,| MPR+R | 2.3 | 8.0 | 12.4 | 7.6 | 10.7 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=119,125,130) | Cycle 7 - approximately Month 7 (n=99,111,111) | Cycle 10 - approximately Month 10 (n=87,93,96) | Cycle 13 - approximately Month 13 (n=75,72,83) | Cycle 16 - approximately Month 16 (n=64,52,63) |
|---|
| MPp+p | -5.6 | -5.7 | -8.0 | -4.8 | -6.4 |
,| MPR+p | 1.9 | -5.7 | -5.4 | -8.8 | -16.0 |
,| MPR+R | 1.7 | -3.7 | -5.0 | -6.2 | -7.8 |
Kaplan Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Central Adjudication Committee (CAC)
"Data as of 11 May 2010 cutoff. PFS was calculated as the time from randomization to the earlier of the first documentation of progressive disease (PD) as determined by the CAC, or death on study due to any cause. PD was based on the European Group for Blood and Marrow Transplantation/International Bone Marrow Transplant Registry/Autologous Bone Marrow Transplant Registry [EBMT/IBMTR/ABMTR] criteria.~PD criteria includes increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia." (NCT00405756)
Timeframe: up to 165 weeks
| Intervention | weeks (Median) |
|---|
| MPR+R | 136.1 |
| MPR+p | 62.1 |
| MPp+p | 56.1 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea and Vomiting Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=120,127,130) | Cycle 7 - approximately Month 7 (n=99,112,112) | Cycle 10 - approximately Month 10 (n=87,95,97) | Cycle 13 - approximately Month 13 (n=75,72,83) | Cycle 16 - approximately Month 16 (n=64,52,62) |
|---|
| MPp+p | -0.0 | 0.7 | 0.3 | -0.4 | -1.3 |
,| MPR+p | -1.3 | -0.7 | -1.4 | -3.0 | -4.2 |
,| MPR+R | 3.3 | 0.5 | 1.9 | 0.7 | 1.0 |
Time to First Response
Data as of 11 May 2010 cutoff. Time to first response was defined as the time from start of treatment until first response as assessed by the Central Assessment Committee (CMC) based on European Group for Blood and Marrow Transplantation (EBMT) criteria. (NCT00405756)
Timeframe: Up to 66 weeks
| Intervention | weeks (Mean) |
|---|
| MPR+R | 10.0 |
| MPR+p | 9.3 |
| MPp+p | 16.2 |
Change From Baseline to Cycles 4, 7, 10, 13 and 16 in European Organization for Research and Treatment of Cancer Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
Data as of 11 May 2010 cutoff. EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems. (NCT00405756)
Timeframe: Baseline (Day 0), Months 4, 7, 10, 13, 16
| Intervention | units on a scale (Mean) |
|---|
| Cycle 4 - approximately Month 4 (n=118,124,128) | Cycle 7 - approximately Month 7 (n=100,109,111) | Cycle 10 - approximately Month 10 (n=87,94,96) | Cycle 13 - approximately Month 13 (n=75,73,83) | Cycle 16 - approximately Month 16 (n=64,53,63) |
|---|
| MPp+p | -5.0 | -5.7 | -1.7 | -6.8 | -3.7 |
,| MPR+p | -1.6 | -6.4 | -2.5 | 0.9 | -0.6 |
,| MPR+R | 2.0 | -1.0 | -5.0 | -4.9 | -4.7 |
Confirmed Anti-tumor Response Rate (Complete Response and Partial Response) to the Combination of Bevacizumab and Lenalidomide
Patient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria). Responses were analyzed by descriptive statistics and summarized in tabular format (frequency tables). Furthermore, two-sided 95% confidence intervals for the proportions of subjects with a confirmed anti-tumor response were computed using the method proposed by Chang, which takes into account the multiplicity problem associated with the two-stage testing procedure. The objective response rate was estimated by using Whitehead's bias-adjustment approach. (NCT00410605)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab, Dexamethasone, and Lenalidomide | 64 |
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at Baseline
A Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients. (NCT00410605)
Timeframe: Baseline
| Intervention | mg per liter (Mean) |
|---|
| IL-6 level range | MIP-1 level range | VEGF level range | VEGFR1 level range | VEGFR2 level range |
|---|
| Bevacizumab, Dexamethasone, and Lenalidomide | 17.2 | 0.039 | 0.084 | 0.12 | 8.85 |
Toxicity and Tolerability of the Bevacizumab and Lenalidomide Combination
Adverse events/toxicities were collected during regular clinical visits. Confidence intervals for the estimate of the true number of patients suffereing from grade 3 or 4 toxicities per common terminology criteria were calculated using the Wilson interval. Ninety-five percent confidence intervals for the proportions of patients with complications (grade 3 or higher toxicities) were constructed. (NCT00410605)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab, Dexamethasone, and Lenalidomide | 72 |
Progression Free Survival (Time to Progression)
Patient response to the treatment were determined by the definitions for complete response, partial response, marginal response, stable disease, and progressive disease outlined by IMBTR/ABMTR (Blade criteria). Progression free survival was summarized using point estimates of the median time to progression and associated 95% confidence intervals. The data was presented graphically using Kaplan-Meier plots. Exploratory analysis, including multivariate Cox regression with demographic variables and markers of myeloma activity as covariates was performed. (NCT00410605)
Timeframe: up to five years
| Intervention | months (Median) |
|---|
| Bevacizumab, Dexamethasone, and Lenalidomide | 9 |
Effect of Bev/Rev on Markers of Myeloma Activity in Myeloma Cells and Stromal Cells at 3 Months Post-baseline
A Wilconxon signed-rank test conducted to determine if biomarker levels differed between baseline levels and those after three full cycles of treatment for all patients. (NCT00410605)
Timeframe: Up to Course 4 Day 1 (3 Months Post-baseline)
| Intervention | mg per liter (Mean) |
|---|
| IL-6 level range | MIP-1 level range | VEGF level range | VEGFR1 level range | VEGFR2 level range |
|---|
| Bevacizumab, Dexamethasone, and Lenalidomide | 5.5 | 0.047 | 0.054 | 0.12 | 8.17 |
Progression-free Survival as Determined by Central Review
"Kaplan-Meier estimate of progression-free survival is defined as start of study drug therapy to the first observation of progressive disease or death due to any cause, whichever comes first.~Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article.~Progressive Disease(PD): Appearance of new lesion during/end of therapy; >=50% increase from lowest measurement in SPD." (NCT00413036)
Timeframe: Up to 1459 days
| Intervention | Months (Median) |
|---|
| Lenalidomide | 4.5 |
Duration of Response as Determined by Central Review
"Kaplan-Meier estimates for the duration of response were calculated for responders and defined as the time from at least a partial response (PR) to progression of disease (PD) or death due to Non-Hodgkin's lymphoma.~For response assessment criteria (per Cheson, 1999) see the primary outcome measure in this results posting." (NCT00413036)
Timeframe: Up to 1459 days
| Intervention | Months (Median) |
|---|
| Lenalidomide | 18.4 |
Participants Categorized by Best Response as Determined by Central Review
"Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definitions, refer to Cheson article.~Complete Response(CR): Complete disappearance of all detectable disease and disease-related symptoms if present before therapy; normalization of lab abnormalities assignable to NHL. If bone marrow involved before treatment, must be cleared on repeat biopsy.~Complete Response Unconfirmed(CRu): CR, with one of the following: 1)residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters(SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2)indeterminate bone marrow.~Partial Response(PR): >50% decrease in 6 largest nodes or nodal masses. Nodes selected according to Cheson.~Stable Disease(SD): Less than PR, but not progressive disease.~Progressive Disease(PD): Appearance of new lesion during/end of therapy; >=50% increase from lowest measurement in SPD." (NCT00413036)
Timeframe: Up to 1459 days
| Intervention | Participants (Number) |
|---|
| Complete Response (CR) | Complete Response Unconfirmed (CRu) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease |
|---|
| Lenalidomide | 7 | 21 | 40 | 71 | 78 |
Time to Progression as Determined by Central Review
"Kaplan-Meier estimate of time-to-progression is calculated as time from the start of study drug therapy to the first observation of disease progression.~Response assessed according to Cheson, Journal of Clinical Oncology, 1999. Full definition of progressive disease, refer to Cheson article.~Progressive Disease(PD): Appearance of new lesion during/end of therapy; >=50% increase from lowest measurement in SPD." (NCT00413036)
Timeframe: Up to 1459 days
| Intervention | Months (Median) |
|---|
| Lenalidomide | 4.5 |
Time to First Venous Thromboembolic Treatment-Emergent Adverse Event (TEAE)
Time between first dose and when a TEAE for venous thromboembolic event was reported. The mean is the univariate mean without adjusting for censoring. The treatment duration was used for censored participants. (NCT00420849)
Timeframe: up to 124 weeks
| Intervention | weeks (Mean) |
|---|
| Lenalidomide Plus Dexamethasone | 26.5 |
Time to First Peripheral Neuropathy Treatment-Emergent Adverse Event (TEAE)
Time between first dose and when a TEAE for peripheral neuropathy was reported. The mean is the univariate mean without adjusting for censoring. The treatment duration was used for censored participants. (NCT00420849)
Timeframe: up to 124 weeks
| Intervention | weeks (Mean) |
|---|
| Lenalidomide Plus Dexamethasone | 25.6 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the side effects scale = higher level of symptomatology. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 4.9 |
| Lenalidomide - Subpopulation From UK + Ireland | 4.7 |
| Lenalidomide - Subpopulation From Spain | 2.0 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 5.8 |
| Lenalidomide - Subpopulation From UK + Ireland | 3.4 |
| Lenalidomide - Subpopulation From Spain | 4.4 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -2.4 |
| Lenalidomide - Subpopulation From UK + Ireland | -1.2 |
| Lenalidomide - Subpopulation From Spain | -3.9 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale. For the body image scale, higher scores = better body image. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -4.3 |
| Lenalidomide - Subpopulation From UK + Ireland | -2.0 |
| Lenalidomide - Subpopulation From Spain | -5.3 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Social Functioning Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of social functioning. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -5.2 |
| Lenalidomide - Subpopulation From UK + Ireland | -5.3 |
| Lenalidomide - Subpopulation From Spain | -3.1 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Role Functioning Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of role functioning. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -2.4 |
| Lenalidomide - Subpopulation From UK + Ireland | -1.5 |
| Lenalidomide - Subpopulation From Spain | -2.6 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Physical Functioning Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -3.6 |
| Lenalidomide - Subpopulation From UK + Ireland | -2.9 |
| Lenalidomide - Subpopulation From Spain | -1.8 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Pain Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the pain scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -3.9 |
| Lenalidomide - Subpopulation From UK + Ireland | -5.2 |
| Lenalidomide - Subpopulation From Spain | -6.6 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Nausea/Vomiting Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the nausea/vomiting scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 1.0 |
| Lenalidomide - Subpopulation From UK + Ireland | 0.1 |
| Lenalidomide - Subpopulation From Spain | -2.2 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Insomnia Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the insomnia scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -3.8 |
| Lenalidomide - Subpopulation From UK + Ireland | 2.2 |
| Lenalidomide - Subpopulation From Spain | -1.8 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Quality of Life Scale
EORTQ QLC-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better quality of life. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 1.1 |
| Lenalidomide - Subpopulation From UK + Ireland | -1.8 |
| Lenalidomide - Subpopulation From Spain | -2.2 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the fatigue scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 2.6 |
| Lenalidomide - Subpopulation From UK + Ireland | 5.3 |
| Lenalidomide - Subpopulation From Spain | 1.0 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Emotional Functioning Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of emotional functioning. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -0.2 |
| Lenalidomide - Subpopulation From UK + Ireland | -4.0 |
| Lenalidomide - Subpopulation From Spain | -0.7 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Dyspnoea Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the dyspnoea scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 2.7 |
| Lenalidomide - Subpopulation From UK + Ireland | 2.7 |
| Lenalidomide - Subpopulation From Spain | -0.9 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Diarrhea Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the diarrhea scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 8.6 |
| Lenalidomide - Subpopulation From UK + Ireland | 8.1 |
| Lenalidomide - Subpopulation From Spain | 9.0 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Constipation Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the constipation scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 1.1 |
| Lenalidomide - Subpopulation From UK + Ireland | 7.9 |
| Lenalidomide - Subpopulation From Spain | 2.6 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Cognitive Functioning Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score = better level of cognitive functioning. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | -1.9 |
| Lenalidomide - Subpopulation From UK + Ireland | -4.9 |
| Lenalidomide - Subpopulation From Spain | 3.5 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Appetite Loss Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a symptom scale like the appetite loss scale = higher level of symptomatology/problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 0.4 |
| Lenalidomide - Subpopulation From UK + Ireland | 3.3 |
| Lenalidomide - Subpopulation From Spain | -4.5 |
Change From Baseline to Week 24 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Financial Problems Scale
EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life in cancer patients. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score for a problem scale like the financial problems scale = higher level of financial problems. (NCT00420849)
Timeframe: Baseline (Day 0), Week 24
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide - Subpopulation From Austria + Australia | 2.0 |
| Lenalidomide - Subpopulation From UK + Ireland | 0.8 |
| Lenalidomide - Subpopulation From Spain | 0.9 |
Participants With Adverse Events of Special Interest: Venous Thromboembolic Events
Number of participants with at least one venous thromboembolic treatment-emergent adverse event (TEAE), and number of participants reporting AEs coded to preferred terms that comprise the search terms for venous thromboembolic events in MedDRA version 9.0 are listed. A participant with multiple occurrences of a TEAE was counted only once for that category. (NCT00420849)
Timeframe: up to 124 weeks
| Intervention | participants (Number) |
|---|
| At least one venous thromboembolic event | Deep vein thrombosis | Pulmonary embolism | Thrombophlebitis | Venous thrombosis limb |
|---|
| Lenalidomide Plus Dexamethasone | 60 | 38 | 23 | 7 | 1 |
Participants With Adverse Events of Special Interest: Peripheral Neuropathy
Number of participants with at least one peripheral neuropathy treatment-emergent adverse event (TEAE), and number of participants reporting AEs coded to preferred terms that comprise the search terms for peripheral neuropathy in MedDRA version 9.0 are listed. A participant with multiple occurrences of a TEAE was counted only once for that category. (NCT00420849)
Timeframe: up to 124 weeks
| Intervention | participants (Number) |
|---|
| At least one TEAE of peripheral neuropathy | Neuropathy peripheral | Peripheral sensory neuropathy | Neuralgia | Peripheral motor neuropathy | Polyneuropathy | Sensory disturbance |
|---|
| Lenalidomide Plus Dexamethasone | 84 | 46 | 33 | 5 | 2 | 2 | 1 |
Overall Incidence of Treatment-emergent Adverse Events (TEAEs), by Severity, Seriousness, and Relationship to Treatment
"Counts of study participants who had treatment-emergent adverse events (TEAEs) defined as any reported AE that started on or after the first day of study drug dosing. A participant with multiple occurrences of an adverse event within a category is counted only once in that category.~National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) was used by investigators to assess TEAEs. Severity scale ranges from 0 (none) to 5 (death). Grade 3=severe AE; Grade 4=life threatening or disabling AE; Grade 5=death." (NCT00420849)
Timeframe: up to 123 weeks
| Intervention | participants (Number) |
|---|
| At least one treatment-emergent AE (TEAE) | At least one TEAE related to study drug | At least one TEAE with severity grade of 3 or 4 | At least one serious AE (SAE) |
|---|
| Lenalidomide Plus Dexamethasone | 586 | 519 | 471 | 340 |
Kaplan-Meier Estimate of Duration of Response
Duration of response was calculated for responders and defined as the time from the first observation of a response (e.g., the first time that the appropriate decrease in M-protein level was observed for confirmed responders) to the first documented progression or relapse. Response duration was censored at the last adequate assessment showing evidence of no progression. (NCT00424047)
Timeframe: Up to data cut off of 03 August 2005; up to 24 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 67.6 |
| Placebo Plus Dexamethasone | 33.3 |
Kaplan-Meier Estimate of Time to Tumor Progression (TTP) (Later Cut-off Date of 02 Mar 2008)
Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. (NCT00424047)
Timeframe: From randomization up to cut-off date of 02 March 2008; up to 51 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 52.4 |
| Placebo Plus Dexamethasone | 20.1 |
Kaplan-Meier Estimate of Overall Survival (OS) (Later Cut-off Date of 02 March 2008)
OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT00424047)
Timeframe: Randomization to data cut off of 02 March 2008; up to 51 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 161.9 |
| Placebo Plus Dexamethasone | 133.3 |
Kaplan-Meier Estimate of Duration of Response (Cut-off at a Later Date of 03 March 2008)
Duration of response was calculated for responders and defined as the time from the first observation of a response (e.g., the first time that the appropriate decrease in M-protein level was observed for confirmed responders) to the first documented progression or relapse. Response duration was censored at the last adequate assessment showing evidence of no progression. (NCT00424047)
Timeframe: Up to data cut off of 03 Mar 2008; up to 51 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 68.1 |
| Placebo Plus Dexamethasone | 33.3 |
Kaplan-Meier Estimate of Time to Tumor Progression (TTP)
Time to progression was calculated as the time from randomization to the first occurrence of disease progression, as determined by a detailed review of all the myeloma response assessment data using the Bladé criteria (Bladé, 1998). Disease progression was also based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. (NCT00424047)
Timeframe: From randomization up to cut-off date of 03 August 2005; up to 24 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 52.1 |
| Placebo Plus Dexamethasone | 20.1 |
Number of Participants With Adverse Events (AE)
"An AE is any sign, symptom, illness, or diagnosis that appears or worsens during the course of the study. Treatment-emergent AEs (TEAEs) are any AE occurring or worsening on or after the first treatment of the study drug and within 30 days after the last cycle end date of study drug. A serious AE = any AE which results in death; is life-threatening; requires or prolongs existing inpatient hospitalization; results in persistent or significant disability is a congenital anomaly/birth defect; constitutes an important medical event.~The severity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE, Version 2.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death." (NCT00424047)
Timeframe: From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 25 June 2013; up to 90 months
| Intervention | participants (Number) |
|---|
| ≥ 1 Adverse Event | ≥ 1 Serious Adverse Event | ≥ 1 AE leading to study drug discontinuation | ≥ 1 AE leading to dose reduction or interruption | ≥ 1 Drug-Related Adverse Event | ≥ 1 Drug-Related Serious Adverse Event | ≥Death within ≤ 30 days of last dose of study drug | ≥ 1 Grade 1 or Higher Adverse Event | ≥ 1 Grade 2 or Higher Adverse Event | ≥ 1 Grade 3 or Higher Adverse Event | ≥ 1 Grade 4 or Higher Adverse Event |
|---|
| Lenalidomide Plus Dexamethasone | 176 | 105 | 46 | 137 | 160 | 54 | 17 | 176 | 168 | 146 | 52 |
,| Placebo Plus Dexamethasone | 175 | 79 | 31 | 100 | 151 | 30 | 20 | 175 | 167 | 119 | 37 |
Kaplan-Meier Estimate of Overall Survival (OS)
OS was calculated as the time from randomization to death from any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT00424047)
Timeframe: Randomization to data cut off of 03 August 2005; up to 24 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide Plus Dexamethasone | NA |
| Placebo Plus Dexamethasone | NA |
Myeloma Response Rates Based on the Reviewers Best Response Assessment (Later Cut-off Date of 02 March 2008)
Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma. (NCT00424047)
Timeframe: Randomization to data cut-off of 02 Mar 2008; up to 51 months
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluable (NE) those without response data |
|---|
| Lenalidomide Plus Dexamethasone | 17.0 | 42.6 | 28.4 | 3.4 | 8.5 |
,| Placebo Plus Dexamethasone | 4.0 | 19.4 | 56.6 | 14.3 | 5.7 |
Summary of Myeloma Response Rates Based on Best Response Assessment
Complete Response (CR): Disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks . Remission Response (RR):75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR): 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD): Criteria for PR or PD have not been met. Plateau Phase: If PR, stable monoclonal paraprotein values (within 25% above or below nadir)/stable soft tissue plasmacytomas maintained for at least 3 months. Progressive Disease (PD): Reappearance of serum or urinary monoclonal paraprotein on immunofixation or electrophoresis on two consecutive occasions at least one week apart. Increase of percentage of plasma cells in bone marrow aspirate or biopsy to ≥ 5%. Development of at least one new lytic bone lesion or soft tissue plasmacytoma. (NCT00424047)
Timeframe: Randomization to 03 August 2005; up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Evaluable (NE) those without response data |
|---|
| Lenalidomide Plus Dexamethasone | 15.3 | 43.8 | 29.0 | 2.8 | 9.1 |
,| Placebo Plus Dexamethasone | 4.0 | 19.4 | 56.6 | 14.3 | 5.7 |
To Establish the Overall Response Rate Measured at 24 Weeks After First Dose of Lenalidomide Using This Dosing Regimen
To establish the overall response rate based on peripheral blood measures (absolute neutrophil count, platelets, and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after first dose of lenalidomide using this dosing regimen (NCT00439231)
Timeframe: 24 weeks of lenalidomide therapy
| Intervention | participants (Number) |
|---|
| Complete response | Partial response | No response |
|---|
| CLL Subject Response Rate After Lenalidomide Therapy | 0 | 5 | 28 |
6B Antibody Response to Prevnar Vaccine in Peripheral Blood
Serum IgG levels against the PVC serotype were measured by ELISA (NCT00445484)
Timeframe: basline and 8 weeks after second vaccination
| Intervention | fold change (Mean) |
|---|
| Vaccine Started 14 Days Prior to Lenalidomide | 3.69 |
| Vaccine Started 45 Days After Lenalidomide | 7.58 |
14F Antibody Response to Prevnar Vaccine in Peripheral Blood
Serum IgG levels against the PVC serotype were measured by ELISA (NCT00445484)
Timeframe: basline and 8 weeks after second vaccination
| Intervention | fold change (Mean) |
|---|
| Vaccine Started 14 Days Prior to Lenalidomide | 9.42 |
| Vaccine Started 45 Days After Lenalidomide | 11.95 |
19F Antibody Response to Prevnar Vaccine in Peripheral Blood
Serum IgG levels against the PVC serotype were measured by ELISA (NCT00445484)
Timeframe: basline and 8 weeks after second vaccination
| Intervention | fold change (Mean) |
|---|
| Vaccine Started 14 Days Prior to Lenalidomide | 2.025 |
| Vaccine Started 45 Days After Lenalidomide | 2.12 |
23F Antibody Response to Prevnar Vaccine in Peripheral Blood
Serum IgG levels against the PVC serotype were measured by ELISA (NCT00445484)
Timeframe: basline and 8 weeks after second vaccination
| Intervention | fold change (Mean) |
|---|
| Vaccine Started 14 Days Prior to Lenalidomide | 4.1 |
| Vaccine Started 45 Days After Lenalidomide | 2.42 |
Time to Disease Progression
International Myeloma Working Group Uniform Response Criteria was used (NCT00445692)
Timeframe: Up to 10.25 years
| Intervention | months (Median) |
|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | 30.5 |
Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3
(NCT00445692)
Timeframe: First year of therapy
| Intervention | episodes (Number) |
|---|
| Neutropenia | Thrombocytopenia | Deep venous thrombus/Pulmonary Embolism | Anemia | Pneumonia | Upper respiratory infections | Sinusitis/acute otitis media | Epiglottic appendagitis | Cellulitis | Clostridium difficile colitis | Vaginitis | Peripheral neuropathy | Dermal leukocytic vasculitis | Secondary cancer Acute Myeloid Leukemia | Re-occurrence of skin cancer |
|---|
| Treatment (Clarithromycin, Dexamethasone, Lenalidomide) | 6 | 1 | 1 | 1 | 4 | 12 | 3 | 1 | 3 | 1 | 3 | 10 | 1 | 1 | 1 |
Ratio of Change in Immune Response From Baseline
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the ratio of BDCA-2 to BDCA-1 cells (NCT00460031)
Timeframe: Week 8
| Intervention | ratio (Mean) |
|---|
| Ketoconazole Plus Lenalidomide | -0.39 |
Change in Immune Response From Baseline
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the levels of CD4+ FoxP3+ Regulatory T cells (NCT00460031)
Timeframe: Week 8
| Intervention | cells/ul (Mean) |
|---|
| Ketoconazole Plus Lenalidomide | 0.18 |
Time to Progression
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) >= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease. (NCT00460031)
Timeframe: One year (12 months) after start of treatment
| Intervention | Months (Median) |
|---|
| Ketoconazole Plus Lenalidomide | 3 |
Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) >= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease. (NCT00460031)
Timeframe: 28 days
| Intervention | participants (Number) |
|---|
| Partial Response | Progressive Disease | Stable Disease |
|---|
| Ketoconazole Plus Lenalidomide | 7 | 7 | 9 |
Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0
Patients will be evaluated for toxicity every 2 weeks during the first cycle. Thereafter, evaluations will be done every 28 days or more frequently if clinically indicated. (NCT00460031)
Timeframe: Up to 30 days after discontinuation of treatment
| Intervention | participants (Number) |
|---|
| Ketoconazole Plus Lenalidomide | 19 |
Response to Treatment
"In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following:~CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal.~PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required." (NCT00466921)
Timeframe: After cycle 4 of treatment (1 cycle =28 days)
| Intervention | participants (Number) |
|---|
| CR | PR |
|---|
| Lenalidomide | 0 | 9 |
Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0
"Toxicity is defined as the number of patients who patients who experienced an adverse event that was determined to be at least possibly related to study drug and determined to be a grade 3 or higher in severity as assessed by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where generally:~Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE" (NCT00466921)
Timeframe: From treatment initiation until up to 30 days post treatment with possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of treatment permitted if meeting response criteria
| Intervention | patients (Number) |
|---|
| Fatigue (grade 3) | Infection (grade 3) | Leukopenia (grade 3) |
|---|
| Lenalidomide | 7 | 1 | 1 |
Progression-free Survival (PFS)
"PFS is defined from the time of treatment initiation until documentation of progressive disease or death from any cause.~Progressive disease is defined as (PD) ≥25% increase in CA ratio, ≥25% increase in no. or area of clinically abnormal lymph nodes/new tumors/new pathologically positive lymph nodes/visceral disease/an increase >25% in no. of Sézary cells." (NCT00466921)
Timeframe: From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years)
| Intervention | months (Median) |
|---|
| Lenalidomide | 8 |
Duration of Response (DOR)
DOR is defined as time of initial documentation of response to the time of documentation of progression in patients who achieve either a complete response (CR) and partial response (PR) (NCT00466921)
Timeframe: From time of initial response until progressive disease (up to approximately 1 year)
| Intervention | months (Median) |
|---|
| Lenalidomide | 10 |
Overall Survival (OS) at 3 Years
OS was defined as the time from registration to death due to any cause. Patients who were alive were censored at date of last follow-up. The overall survival at 3 years (a percentage) is reported below. (NCT00477750)
Timeframe: registration to death (up to 3 years)
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | 58 |
Duration of Response (DOR)
Duration of response was calculated from documentation of first response to date of progression in the subset of patients who responded. Patients without progression were censored at the date of last tumor evaluation. (NCT00477750)
Timeframe: from first response to progression or death (up to 3 years)
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | 16.3 |
Progression-free Survival
"Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression was defined as any one or more of the following:~An increase of 25% from lowest confirmed response in:~Serum M-component (absolute increase >= 0.5g/dl)~Urine M-component (absolute increase >= 200mg/24hour~Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl~Bone marrow plasma cell percentage (absolute increase of >=10%)" (NCT00477750)
Timeframe: registration to progressive disease (up to 3 years)
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | 21.4 |
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. (NCT00477750)
Timeframe: Every cycle during treatment up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | 33 | 67 | 0 |
Patients With Overall Confirmed Response
"Response that was confirmed on 2 consecutive evaluations.>~Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and <=5% plasma cells in bone marrow>~Very Good Partial Response (VGPR): >=90% reduction in serum M-spike, Urine M-spike <100mg per 24 hours>~Partial Response (PR): >=50% reduction in serum M-spike, Urine M-spike >=90% reduction or < 200mg per 24 hours, or >=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells" (NCT00477750)
Timeframe: Every cycle during treatment
| Intervention | participants (Number) |
|---|
| CR | VGPR | PR |
|---|
| Treatment (Lenalidomide, Melphalan, Prednisone) | 3 | 5 | 10 |
Overall Survival (OS)
OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method. (NCT00478218)
Timeframe: up to 5 years
| Intervention | months (Median) |
|---|
| LCD (Cyclophosphamide 300 mg/m^2) | NA |
| LCD (Cyclophosphamide 300 mg) | NA |
Duration of Response (DOR)
Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. The median DOR with 95%CI was estimated using the Kaplan Meier method. (NCT00478218)
Timeframe: up to 5 years
| Intervention | months (Median) |
|---|
| LCD (Cyclophosphamide 300 mg/m^2) | 26.1 |
| LCD (Cyclophosphamide 300 mg) | NA |
Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment
"Response that was confirmed on 2 consecutive evaluations during treatment~Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM)~Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM~Partial Response PR): >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels" (NCT00478218)
Timeframe: Duration of Treatment (up to 5 years)
| Intervention | participants (Number) |
|---|
| LCD (Cyclophosphamide 300 mg/m^2) | 28 |
| LCD (Cyclophosphamide 300 mg) | 16 |
Progression-free Survival (PFS)
"PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.> Progression was defined as any one or more of the following:> An increase of 25% from lowest confirmed response in:>~Serum M-component (absolute increase >= 0.5g/dl)>~Urine M-component (absolute increase >= 200mg/24hour>~Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl>~Bone marrow plasma cell percentage (absolute increase of >=10%)" (NCT00478218)
Timeframe: up to 5 years
| Intervention | months (Median) |
|---|
| LCD (Cyclophosphamide 300 mg/m^2) | 27 |
| LCD (Cyclophosphamide 300 mg) | NA |
Participants With Treatment-emergent Adverse Experiences (TEAEs)
"Counts of study participants who had treatment-emergent adverse events (TEAEs) defined as any reported AE that started on or after the first day of study drug dosing. A participant with multiple occurrences of an adverse event within a category is counted only once in that category.~National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) was used by investigators to assess TEAEs. Severity scale ranges from 0 (none) to 5 (death). Grade 3=severe AE; Grade 4=life threatening or disabling AE; Grade 5=death." (NCT00478777)
Timeframe: up to 8 months
| Intervention | participants (Number) |
|---|
| >=1 TEAE | >=1 TEAE related to study drug | >=1 NCI CTCAE grade 3 or 4 TEAE | >=1 NCI CTCAE grade 3 or 4 TEAE related to drug | >=1 serious AE (SAE) | >=1 study drug related SAE | Discontinued due to TEAE | Discontinued due to TEAE related to study drug | TEAE leading to dose reduction | TEAE leading to dose interruption | Deaths |
|---|
| Lenalidomide Plus Dexamethasone | 139 | 119 | 105 | 83 | 79 | 48 | 32 | 21 | 35 | 64 | 79 |
Participant's Best Overall Response Based on the European Group for Blood and Marrow Transplantation (EBMT) Myeloma Response Criteria
"Best overall response was calculated as the best assessment from all cycles (including treatment discontinuation visit) and follow-up. The response rate was summarized as complete response (CR), partial response (PR), stable disease (SD), progression (PD), response not evaluable, and derived categories (PR+CR) and (PR+CR+SD).~CR is negative immunofixation on both serum and urine maintained for 6 weeks straight. PR is a 50% decrease in serum paraprotein maintained for 6 weeks straight. SD is serum paraprotein values within 25% of baseline." (NCT00478777)
Timeframe: Up to 827 days
| Intervention | participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Not evaluable (NE) | CR + PR | CR + PR + SD |
|---|
| Lenalidomide Plus Dexamethasone | 6 | 97 | 30 | 3 | 8 | 103 | 133 |
Kaplan Meier Estimate for Time to Disease Progression
"Time to disease progression (TTP) was based on the European Group for Blood and Marrow Transplantation (EBMT) myeloma response determination criteria developed by Bladé (Bladé, 1998). TTP is a Kaplan Meier estimate of the time from randomization to the first documentation of progressive disease.~Progressive disease based on increasing monoclonal paraprotein levels require a confirmatory value one week apart. Disease progression can also be based on bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia." (NCT00478777)
Timeframe: up to 827 days
| Intervention | days (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 214.0 |
Response Rate (Complete and Partial Response)
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. (NCT00482911)
Timeframe: 2 years
| Intervention | Participants (Number) |
|---|
| Complete Response | Partial Response |
|---|
| Cohort 1-lenalidomide & Cyclophosphamide | 0 | 0 |
,| Cohort 2-sunitinib & Cyclophosphamide | 0 | 0 |
Toxicity
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module. (NCT00482911)
Timeframe: 16 months
| Intervention | Participants (Number) |
|---|
| Cohort 1-lenalidomide & Cyclophosphamide | 3 |
| Cohort 2-sunitinib & Cyclophosphamide | 8 |
Number of Patients With Stringent Complete Response Rate
Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | participants (Number) |
|---|
| V-DR | 7 |
| VDCR | 6 |
| V-DC | 3 |
| VDC-mod | 5 |
Overall Survival
Overall survival is defined as time from the date of randomization to the date of death (NCT00507442)
Timeframe: Up to 48 weeks or until death
| Intervention | days (Median) |
|---|
| V-DR | NA |
| VDCR | NA |
| V-DC | NA |
| VDC-mod | NA |
Probability of 1-year Survival
(NCT00507442)
Timeframe: survival probability at 1 year after randomization
| Intervention | percentage of patients (Number) |
|---|
| V-DR | 100 |
| VDCR | 91.6 |
| V-DC | 100 |
| VDC-mod | 100 |
Number of Patients With Combined Complete Response and Very Good Partial Response
"Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.~Very good partial response requires serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h" (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | participants (Number) |
|---|
| V-DR | 21 |
| VDCR | 23 |
| V-DC | 13 |
| VDC-mod | 9 |
Time to Disease Progression
"Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease.~Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas." (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | days (Median) |
|---|
| V-DR | NA |
| VDCR | NA |
| V-DC | NA |
| VDC-mod | NA |
Time to Response
Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments. (NCT00507442)
Timeframe: Up to 48 weeks or until disease response
| Intervention | days (Median) |
|---|
| V-DR | 49 |
| VDCR | 50 |
| V-DC | 55 |
| VDC-mod | 49 |
Progression-free Survival
"Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death.~Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas." (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression/death
| Intervention | days (Median) |
|---|
| V-DR | NA |
| VDCR | 631 |
| V-DC | NA |
| VDC-mod | NA |
Duration of Response
"Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments.~Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas." (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | days (Median) |
|---|
| V-DR | NA |
| VDCR | NA |
| V-DC | NA |
| VDC-mod | NA |
Number of Patients With Adverse Events (AEs)
Evaluate the safety and tolerability of the combination therapy (NCT00507442)
Timeframe: From first dose of study drug through the 30 day post-treatment AE assessment visit
| Intervention | participants (Number) |
|---|
| V-DR | 42 |
| VDCR | 65 |
| V-DC | 33 |
| VDC-mod | 17 |
Number of Patients With Complete Response Rate + Near Complete Response Rate
"Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.~Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow." (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | participants (Number) |
|---|
| V-DR | 17 |
| VDCR | 14 |
| V-DC | 10 |
| VDC-mod | 8 |
Number of Patients With Overall Response
"Overall Response includes complete response and partial response.~Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.~Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to < 200 mg per 24 hour." (NCT00507442)
Timeframe: Up to 48 weeks or until disease progression
| Intervention | participants (Number) |
|---|
| V-DR | 35 |
| VDCR | 35 |
| V-DC | 24 |
| VDC-mod | 17 |
Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR])
"CR:~Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria:~Negative immunofixation on the serum and urine at two consecutive times~Disappearance of any soft tissue plasmacytomas~≤5% plasma cells in bone marrow~If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times~VGPR:~Serum and urine M-component detectable by immunofixation but not on electrophoresis OR~>=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP)~If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a >90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria" (NCT00522392)
Timeframe: Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
| Intervention | Proportion of patients (Number) |
|---|
| Arm A (VRD) | 0.625 |
| Arm B (VD) | 0.188 |
Progression-free Survival (PFS)
"Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment.~The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued." (NCT00522392)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
| Intervention | Months (Median) |
|---|
| Arm A (VRD) | NA |
| Arm B (VD) | 17.4 |
Overall Survival (OS)
Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014. (NCT00522392)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years
| Intervention | Months (Median) |
|---|
| Arm A (VRD) | 64.0 |
| Arm B (VD) | NA |
Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI)
The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment. (NCT00522392)
Timeframe: Baseline and 6 months post consolidation treatment
| Intervention | units on a scale (Mean) |
|---|
| Arm A (VRD) | -7.9 |
| Arm B (VD) | -2.6 |
Overall Response Rate (ORR)
ORR defined as number of participants with best response of Complete Response (CR) or Partial Response (PR) out of total number of participants. CR is defined as absence of lymphadenopathy, hepatomegaly or splenomegaly on physical exam. Normal Complete Blood Count (CBC) with polymorphonuclear leukocytes >1500/µL, platelets >100,000/µL, hemoglobin >11.0 g/dL (untransfused); lymphocyte count <5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with <30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. PR requires a 50% decrease in peripheral lymphocyte count from , 50% reduction in lymphadenopathy, and/or 50% reduction in splenomegaly/hepatomegaly for a period of at least two months from completion of therapy. These patients must have one of the following: Polymorphonuclear leukocytes 1,500/µL or 50% improvement ; Platelets >100,000/µL or 50% improvement ; Hemoglobin >11.0 g/dL (untransfused) or 50% improvement from pre-treatment value. (NCT00535873)
Timeframe: From 3 cycles (90 days) up to 6 cycles (approximately 180 days)
| Intervention | participants (Number) |
|---|
| Lenalidomide | 39 |
Complete Response Rate
An improvement in complete response to at least 60% following treatment, assessed using CT scans, clinical/lab examinations, and bone marrow aspirations, as defined by National Cancer Institute Working Group Response Criteria. (NCT00536341)
Timeframe: At 12 weeks during treatment and 2 months post-treatment until disease progression, projected 8 months
| Intervention | participants (Number) |
|---|
| Dose Level 1 | 4 |
| Dose Level 2 | 9 |
Overall Survival
Defined as the time from Day 1 of treatment administration to date of death from any cause, estimated using Kaplan-Meier methods. (NCT00536341)
Timeframe: Every 3 months until treatment discontinuation, expected average of 6 months and then every 6 months thereafter up to 5 years
| Intervention | months (Median) |
|---|
| All Patients | NA |
Number of Adverse Events as a Measure of Safety and Tolerability
Recorded from first treatment until 30 days after last treatment and assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCT00536341)
Timeframe: 63 months
| Intervention | participants (Number) |
|---|
| Fatigue | Neutropenia | Anemia | Leukopenia | Thrombocytopenia | Rash | Nausea | Constipation | Anorexia | Fever | Hyperhidrosis | Arthralgia | Edema Limbs | Pruritus | Back pain | Headache | Chills | Insomnia | Vomiting | Dysgeusia | Abdominal Pain | Allergic Reaction | Diarrhea | Cough | Dizziness | Dyspnea | Hypotension | Myalgia |
|---|
| Dose Level 1 | 8 | 7 | 8 | 7 | 8 | 6 | 7 | 3 | 4 | 3 | 3 | 1 | 3 | 0 | 3 | 1 | 2 | 2 | 2 | 1 | 2 | 4 | 3 | 2 | 2 | 0 | 1 | 2 |
,| Dose Level 2 | 40 | 41 | 34 | 34 | 30 | 27 | 25 | 15 | 12 | 13 | 13 | 14 | 12 | 15 | 11 | 13 | 11 | 11 | 11 | 11 | 9 | 7 | 8 | 8 | 8 | 10 | 9 | 8 |
Progression-Free Survival
Measured from first treatment to disease progression and assessed using Kaplan-Meier methods. (NCT00536341)
Timeframe: Every 3 months during treatment until disease progression and every 6 months thereafter, up to 5 years
| Intervention | months (Median) |
|---|
| All Patients | 24.64 |
Effect of Drug Combination on Multiple Myeloma
Objective response rate, defined according to the International Myeloma Working Group (IMWG) criteria as greater then or equal to a Partial Response (PR). The best response was recorded. The IMWG criteria can be found here: imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/ (NCT00538733)
Timeframe: This was collected from patients for their duration on study treatment. Only the best response was recorded. Best responses were reported at any point of the study, from start of treatment up until removal of study, which occurred up to 57.4 cycles
| Intervention | participants (Number) |
|---|
| sCR (stringent complete response) | VGPR (very good partial response) | PR (partial response) | SD (stable disease) |
|---|
| T-BiRD Therapy (All Patients) | 2 | 9 | 9 | 5 |
Progression Free Survival
"Progression determined using International Myeloma Working Group criteria, as defined below.~An increase of > 25% from lowest response value one or more of the following:~Serum M-component and/or (the absolute increase must be > 0.5 g/dL)*~Urine M-component and/or (the absolute increase must be > 200 mg/24 h)~Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL~Bone marrow plasma cell percentage; the absolute percentage must be > 10%~Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas~Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder *if starting serum M protein is greater then 5 g/dL, absolute increase of 1g/dL is sufficient to determine relapse." (NCT00538733)
Timeframe: From start of treatment, to the date of first progression
| Intervention | months (Median) |
|---|
| T-BiRD Therapy (All Patients) | 35.6 |
Event Free Survival
(NCT00538733)
Timeframe: from baseline to the time of first event that lead to removal from study (defined as progression, death, withdrawal of consent, or removal for toxicity)
| Intervention | months (Median) |
|---|
| T-BiRD Therapy (All Patients) | 21.5 |
Effect of Drug Combination on Multiple Myeloma
The maximum response for all patients that were treated on study. Maximum response was assessed using the International myeloma working group (IMWG) guidelines for response. http://imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/ (NCT00538824)
Timeframe: The best response for all patients at any point were assessed for patients that were treated on study, from start of treatment up to 20 weeks
| Intervention | participants (Number) |
|---|
| partial response (PR) | minimal response (MR) | progression of disease |
|---|
| DexTR (All Patients) | 2 | 1 | 2 |
Relapse Free Survival (RFS)
(NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | months (Median) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 3.78 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 3.93 |
Safety and Tolerability of Lenalidomide Therapy as Measured by the Number of Participants Who Experience Each Adverse Event (Grade 3 or 4 Adverse Events Only) Refractory cHL.
"Adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0~The higher the grade the worse the adverse event was considered" (NCT00540007)
Timeframe: 30 days following the completion of treatment
| Intervention | participants (Number) |
|---|
| Neutropenia | Leukopenia | Anemia | Lymphopenia | Thrombocytopenia | Fatigue | AST | ALT | Bilirubin | Sensory neuropathy | Dehydration | Infection without neutropenia | Infection with neutropenia | Edema | Dyspnea | Pleural effusion | Alkaline phosphatase | Abdominal pain | Low potassium | Low sodium | Low albumin | Low calcium | High calcium | Low phosphorus | Hearing loss | Thrombosis/embolism | Rash | Febrile neutropenia | Pneumonia | High potassium | Hyperuricemia | Confusion | Dizziness | Speech impairment | Chest pain | Extremity pain | Muscle pain | Secondary malignancy - MDS |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 18 | 11 | 10 | 9 | 7 | 3 | 3 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2 | 20 | 13 | 4 | 10 | 8 | 2 | 1 | 1 | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 2 | 1 | 2 | 1 | 1 |
Time to Progression (TTP).
-Time to progression (TTP) is defined as the time from study entry until documented lymphoma progression or death as a result of lymphoma. (NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | months (Median) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 3.68 |
| Cohort 2 | 4.08 |
Duration of Response
-Duration of response: defined as the interval from the date of response (CR or PR) is documented to the date of progression, taking as reference the smallest measurements recorded since the treatment started (NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | months (Median) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 3.68 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 4.08 |
Cytostatic Overall Response Rate
"Cytostatic overall response rate = CR + PR + SD greater than or equal to 6 months~Definitions per 2007 Cheson Lymphoma Response Criteria" (NCT00540007)
Timeframe: From 6 months through 3.5 years after study entry
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 15 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 18 |
Event Free Survival (EFS).
-Event-free survival (time to treatment failure) is measured from the time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death). (NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | months (Median) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 3.78 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 3.93 |
Overall Survival (OS)
Overall survival is defined as the time from entry onto the clinical trial until death as a result of any cause. (NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | months (Median) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 17.434 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 23.717 |
Objective Overall Response Rate (ORR) in Relapsed or Refractory cHL.
"Overall response rate = CR + PR~Definitions per 2007 Cheson Lymphoma Response Criteria" (NCT00540007)
Timeframe: Through 3.5 years from study entry or until disease progression
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1 - Lenalidomide Daily on Days 1-21 | 21.0 |
| Cohort 2 - Lenalidomide Daily on Days 1-28 | 28.6 |
Quality of Life Using the FACT-G Data
"Change from baseline FACT-G scores. The quality of life questionnaire (FACT-G) was given at various timepoints during the study. The values for change from baseline to endpoint are provided.~Physical Well-Being (PWB; sum of 7 items, point range 0-28); Social/Family Well-Being (SWB, sum of 7-items, point range 0-28); Emotional Well-Being (EWB; sum of 6-items, point range 0-24); Functional Well-Being (FWB; sum of 7-items, point range 0-28) ; Fact-G score=sum of PWB, SWB, EWB, FWB, point range 0-108. Note: The higher the score, the better the outcome" (NCT00540644)
Timeframe: baseline and after last cycle (up to 6 cycles)
| Intervention | scores on a scale (Mean) |
|---|
| Physical Well-Being Change from Baseline | Social/Family Well-Being Change from Baseline | Emotional Well-Beling Change from Baseline | Functional Well-Being Change from Baseline | FACT-G Change from Baseline |
|---|
| Extension - Revlimid, Cyclophosphamide, Prednisone | -2.81 | -0.23 | 0.60 | -1.17 | -3.61 |
,| Original Study - Revlimid, Cyclophosphamide, Prednisone | 1.57 | -0.03 | 2.52 | 3.38 | 7.44 |
Duration of CR for Complete Responders
Duration of remission: Defined as the interval from the date complete remission is documented to the date of recurrence (NCT00546897)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Cohort 2 | 10 |
CR With Complete Blood Counts (CRi) Rate
CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 0 |
| Cohort 2 | 4 |
Response Rate (RR)
"RR = as patients obtaining any response (CRm + CRc +CRi + PR).~CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.~CRc = Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).~Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.~Partial remission (PR): Requires" (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| CRm | CRc | CRi | PR |
|---|
| Cohort 1 | 0 | 1 | 0 | 1 |
,| Cohort 2 | 3 | 3 | 4 | 0 |
Morphologic Leukemia Free State
Morphologic leukemia-free state: Defined as < 5% blasts on the BM aspirate with spicules and a count of > 200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 10 |
Morphologic Complete Remission Rate (CRm)
CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 0 |
| Cohort 2 | 3 |
Safety and Tolerability (Removal From Study Due to Adverse Events)
Toxicity will be scored using CTCAE Version 3.0 for toxicity and adverse event reporting (NCT00546897)
Timeframe: 4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)]
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 8 |
Relapse Free Survival (RFS) for Complete Responders
This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. (NCT00546897)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Cohort 2 | 10 |
Progression-free Survival
Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment. It is the percentage of individuals in the group whose disease is likely to remain stable (and not show signs of progression) after a specified duration of time. Progression-free survival rates are an indication of how effective a particular treatment is. (NCT00546897)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Cohort 2 | 2 |
Partial Remission Rate (PR)
Partial remission (PR): Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 0 |
Overall Survival (OS)
Overall survival: Defined as the date of first dose of study drug to the date of death from any cause. (NCT00546897)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Cohort 2 | 4 |
Complete Remission Rate (CRm + CRi + CRc)
"CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.~CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.~Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells)." (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| CRm | CRi | CRc |
|---|
| Cohort 1 | 0 | 0 | 1 |
,| Cohort 2 | 3 | 4 | 3 |
Cytogenetics CR Rate (CRc)
Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 3 |
Number of Participants With an Overall Response Defined as Complete Response and Partial Response
"Response is assessed by investigator according to International Working Group (IWG) criteria.~A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease." (NCT00553644)
Timeframe: Duration of treatment (assessed up to 6 years)
| Intervention | participants (Number) |
|---|
| Treatment (Antiangiogenesis Therapy, Enzyme Inhibitor Therapy) | 21 |
Time to Progression
Time to progression (TTP) is defined as the time from study entry until progression or death due to any cause. The median TTP with 95% CI was estimated using the Kaplan-Meier method. (NCT00553644)
Timeframe: Assessed up to 6 years
| Intervention | years (Median) |
|---|
| Treatment (Antiangiogenesis Therapy, Enzyme Inhibitor Therapy) | 0.58 |
Overall Survival
Overall survival (OS) is defined as the time from study entry until death. The median OS with 95% CI was estimated using the Kaplan-Meier method.. (NCT00553644)
Timeframe: Assessed up to 6 years
| Intervention | years (Median) |
|---|
| Treatment (Antiangiogenesis Therapy, Enzyme Inhibitor Therapy) | 2.17 |
Incidence of Adverse Events
Number of participants who experienced a maximum grade 3, 4 or 5 adverse event. The grading scales found in the revised NCI CTCAE version 4.0 was utilized for adverse event reporting (NCT00553644)
Timeframe: Duration of Treatment (up to 6 years)
| Intervention | participants (Number) |
|---|
| Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Treatment (Antiangiogenesis Therapy, Enzyme Inhibitor Therapy) | 4 | 29 | 17 | 1 |
Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone
The MTD is considered the last dose level combination tested just below the maximum administered dose (MAD) level combination and for which DLTs were observed in less than 33% of participants during the escalation and expansion phase. Please refer to outcome 2 for the complete definition of DLT. If the MTD was not reached at the highest dose administered as defined by protocol, the highest dose (dasatinib 140 mg QD + lenalidomide 25 mg QD) administered was selected for the dose expansion phase of the study. (NCT00560391)
Timeframe: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 |
Number of Participants With Dose-limiting Toxicity (DLT)
DLTs: At least possibly drug-related AEs occurring during the first cycle of treatment and are:GR4 neutropenia >5 days/neutropenic fever;platelet count <10000mm^3 on >1 occasion;GR4 fatigue,or 2-point decline in ECOG performance status;>=GR3 nausea,diarrhea,and vomiting despite medical intervention;Any other clinically significant non-hematologic toxicity of >=GR3 considered not related to underlying MM;Any GR3/4 laboratory abnormality requiring hospitalization;dose interruption of either dasatinib and/or lenalidomide for >15 days due to any toxicity related to treatment with the combination. (NCT00560391)
Timeframe: From the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 1 |
| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 1 |
| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 |
Number of Participants With Minimal Response
Response criteria was based on The International Uniform Response Criteria for Multiple Myeloma (with a slight modification). Minimal Response was achieved when there was 25% to 49% reduction of serum M-Protein, 50% to 89% reduction in 24 hour urinary M-protein which still exceeded 200 mg/24 hour. If the serum and urine M-protein were unmeasurable, 25% to 49% reduction in plasma cells was required. In addition, if present at baseline, a 25% to 49% reduction in the size of soft tissue plasmacytomas was also required. (NCT00560391)
Timeframe: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 |
| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 |
Number of Participants With Partial Response
Partial response was achieved when there was ≥50% reduction of serum M-protein (Mpr)and reduction in 24 hour urinary Mpr by ≥90% or to <200 mg/24 hr. If the serum and urine Mpr were unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the Mpr criteria. If serum, urine Mpr, and serum FLC assay were unmeasurable, ≥50% reduction in plasma cells was required in place of Mpr, provided baseline bone marrow plasma cell percentage was ≥30%; a ≥50% reduction in the size of soft tissue plasmacytomas was also required. (NCT00560391)
Timeframe: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 1 |
| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 1 |
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 2 |
| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 4 |
| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 3 |
Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation
AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4 = Life-threatening or disabling. (NCT00560391)
Timeframe: Baseline (pretreatment), from the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| All deaths | Deaths within 30 days of last dose | All SAEs | Drug-related SAEs | AEs leading to discontinuation | Drug-related AEs leading to discontinuation | All AEs | Drug-related AEs |
|---|
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 | 0 | 2 | 1 | 1 | 0 | 3 | 3 |
,| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 1 | 0 | 5 | 1 | 1 | 0 | 6 | 6 |
,| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 3 | 2 | 9 | 4 | 8 | 7 | 17 | 17 |
,| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 3 | 1 | 3 | 1 | 2 | 2 | 6 | 6 |
,| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 2 | 1 | 2 | 1 | 1 | 0 | 3 | 3 |
Number of Participants With Complete Response and Very Good Partial Response
Response criteria were based on The International Uniform Response Criteria for Multiple Myeloma (with a slight modification). Complete response was achieved when there was negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. Very good partial response was achieved when serum and urine M-component was detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component < 100 mg per 24 hour. (NCT00560391)
Timeframe: Baseline, At the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | participants (Number) |
|---|
| Complete response | Very good partial response | No response | Not reported | Response Undetermined |
|---|
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 | 0 | 1 | 0 | 0 |
,| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 | 1 | 1 | 0 | 0 |
,| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 0 | 3 | 11 | 0 | 0 |
,| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 0 | 0 | 4 | 1 | 0 |
,| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 | 0 | 2 | 0 | 0 |
Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin (TB), and Serum Creatinine (SC)
Grading as per NCI CTCAE Version 3.0 criteria. GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT): GR1=>ULN-2.5*ULN (upper limit of normal); GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4:>20.0*ULN; TB:GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN; SC: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. BL=Baseline; PBL=post baseline. (NCT00560391)
Timeframe: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])
| Intervention | participants (Number) |
|---|
| AST; GR 0 at BL, GR 0 PBL | AST; GR 0 at BL, GR 1 to 2 PBL | AST; GR 0 at BL, GR 3 to 4 PBL | AST; GR 1 to 2 at BL, GR 0 PBL | AST; GR 1 to 2 at BL, GR 1 to 2 PBL | AST; GR 1 to 2 at BL, GR 3 to 4 PBL | High ALT; GR 0 at BL, GR 0 PBL | ALT; GR 0 at BL, GR 1 to 2 PBL | ALT; GR 0 at BL, GR 3 to 4 PBL | ALT; GR 1 to 2 at BL, GR 0 PBL | ALT; GR 1 to 2 at BL, GR 1 to 2 PBL | ALT; GR 1 to 2 at BL, GR 3 to 4 PBL | Total Bilirubin; GR 0 at BL, GR 0 PBL | Total Bilirubin; GR 0 at BL, GR 1 to 2 PBL | Total Bilirubin; GR 0 at BL, GR 3 to 4 PBL | SC; GR 0 at BL, GR 0 PBL | SC; GR 0 at BL, GR 1 to 2 PBL | SC; GR 0 at BL, GR 3 to 4 PBL | SC; GR 1 to 2 at BL, GR 0 PBL | SC; GR 1 to 2 at BL, GR 1 to 2 PBL | SC; GR 1 to 2 at BL, GR 3 to 4 PBL |
|---|
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
,| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 5 | 0 | 0 | 0 | 1 | 0 | 2 | 3 | 0 | 0 | 1 | 0 | 4 | 2 | 0 | 6 | 0 | 0 | 0 | 0 | 0 |
,| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 5 | 8 | 0 | 0 | 3 | 1 | 5 | 9 | 0 | 0 | 2 | 1 | 13 | 4 | 0 | 12 | 3 | 1 | 0 | 0 | 1 |
,| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 4 | 2 | 0 | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 0 | 0 | 5 | 1 | 0 | 4 | 2 | 0 | 0 | 0 | 0 |
,| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 |
Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus
Grading as per NCI CTCAE Version 3.0 criteria. GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Calcium (low): GR1: ULN - 11.5 mg/dL, GR2: >11.5 - 12.5 mg/dL, GR3: >12.5 - 13.5 mg/dL, GR4: >13.5 mg/dL. Magnesium (Low): GR1: NCT00560391)
Timeframe: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])
| Intervention | participants (Number) |
|---|
| High Calcium; GR 0 at BL, GR 0PBL | High Calcium; GR 0 at BL, GR 1 to 2 PBL | High Calcium; GR 0 at BL, GR 3 to 4 PBL | High Calcium; GR 1 to 2 at BL, GR 0 PBL | High Calcium; GR 1 to 2 at BL, GR 1 to 2 PBL | High Calcium; GR 1 to 2 at BL, GR 3 to 4 PBL | Low Calcium; GR 0 at BL, GR 0 PBL | Low Calcium; GR 0 at BL, GR 1 to 2 PBL | Low Calcium; GR 0 at BL, GR 3 to 4 PBL | Low Calcium; GR 1 to 2 at BL, GR 0 PBL | Low Calcium; GR 1 to 2 at BL, GR 1 to 2 PBL | Low Calcium; GR 1 to 2 at BL, GR 3 to 4 PBL | Low Magnesium; GR 0 at BL, GR 0 PBL | Low Magnesium; GR 0 at BL, GR 1 to 2 PBL | Low Magnesium; GR 0 at BL, GR 3 to 4 PBL | Low Magnesium; GR 1 to 2 at BL, GR 0 PBL | Low Magnesium; GR 1 to 2 at BL, GR 1 to 2 PBL | Low Magnesium; GR 1 to 2 at BL, GR 3 to 4 PBL | Low Magnesium; GR Not reported at BL | Low Phosphorus; GR 0 at BL, GR 0 PBL | Low Phosphorus; GR 0 at BL, GR 1 to 2 PBL | Low Phosphorus; GR 0 at BL, GR 3 to 4 PBL | Low Phosphorus; GR 1 to 2 at BL, GR 0 PBL | Low Phosphorus; GR 1 to 2 at BL, GR 1 to 2 PBL | Low Phosphorus; GR 1 to 2 at BL, GR 3 to 4 PBL | Low Phosphorus; GR 3 to 4 at BL, GR 0 PBL | Low Phosphorus; GR 3 to 4 at BL, GR 1 to 2 PBL | Low Phosphorus; GR 3 to 4 at BL, GR 3 to 4 PBL |
|---|
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
,| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 4 | 0 | 0 | 0 | 2 | 0 | 2 | 4 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 1 | 0 | 0 | 3 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 15 | 1 | 0 | 0 | 1 | 0 | 1 | 12 | 2 | 0 | 1 | 1 | 7 | 6 | 1 | 0 | 3 | 0 | 0 | 8 | 2 | 6 | 0 | 0 | 1 | 0 | 0 | 0 |
,| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 4 | 1 | 0 | 0 | 0 | 1 | 2 | 3 | 0 | 0 | 1 | 0 | 2 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone)
The RP2D was based on the MTD which was defined as the maximum combined dose producing dose limiting toxicity (DLT) in < 33% of participants treated at the individual dose levels in the combination. The MTD is considered the last dose level combination tested just below the maximum administered dose (MAD) level combination and for which DLTs were observed in less than or equal to 33% of participants during the escalation and expansion phase. If MTD was not reached Please refer to Outcome Measure 2 for the complete definition of DLT. (NCT00560391)
Timeframe: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
| Intervention | mg (Number) |
|---|
| RP2D of dasatinib in the combination | RP2D of lenalidomide in the combination | RP2D dexamethasone in the combination |
|---|
| All Treated Participants | 140 | 25 | 40 |
Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia
As per NCI CTCAE Version 3.0 criteria. Grade (GR)1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. White blood cell (WBC):GR1=NCT00560391)
Timeframe: Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])
| Intervention | participants (Number) |
|---|
| Leukopenia; GR 0 at BL, GR 0 PBL | Leukopenia; GR 0 at BL, GR 1 to 2 PBL | Leukopenia; GR 0 at BL, GR 3 to 4 PBL | Leukopenia; GR 1 to 2 at BL, GR 0 PBL | Leukopenia; GR 1 to 2 at BL, GR 1 to 2 PBL | Leukopenia; GR 1 to 2 at BL, GR 3 to 4 PBL | Neutropenia; GR 0 at BL, GR 0 PBL | Neutropenia; GR 0 at BL, GR 1 to 2 PBL | Neutropenia; GR 0 at BL, GR 3 to 4 PBL | Neutropenia; GR 1 to 2 at BL, GR 0 | Neutropenia; GR 1 to 2 at BL, GR 1 to 2 PBL | Neutropenia; GR 1 to 2 at BL, GR 3 to 4 PBL | Thrombocytopenia; GR 0 at BL, GR 0 PBL | Thrombocytopenia; GR 0 at BL, GR 1 to 2 PBL | Thrombocytopenia; GR 0 at BL, GR 3 to 4 PBL | Thrombocytopenia; GR 1 to 2 at BL, GR 0 PBL | Thrombocytopenia; GR 1 to 2 at BL, GR 1 to 2 PBL | Thrombocytopenia; GR 1 to 2 at BL, GR 3 to 4 PBL | Anemia; GR 0 at BL, GR 0 PBL | Anemia; GR 0 at BL, GR 1 to 2 PBL | Anemia; GR 0 at BL, GR 3 to 4 PBL | Anemia; GR 1 to 2 at BL, GR 0 PBL | Anemia; GR 1 to 2 at BL, GR 1 to 2 PBL | Anemia; GR 1 to 2 at BL, GR 3 to 4 PBL | Anemia; GR 3 to 4 at BL, GR 0 PBL | Anemia; GR 3 to 4 at BL, GR 1 to 2 PBL | Anemia; GR 3 to 4 at BL, GR 3 to 4 PBL | Anemia; GR Not reported at BL |
|---|
| Dasatinib 100 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Dasatinib 100 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 1 | 2 | 0 | 0 | 0 | 3 | 0 | 3 | 0 | 0 | 0 | 3 | 1 | 3 | 0 | 0 | 1 | 1 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 |
,| Dasatinib 140 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 2 | 6 | 3 | 0 | 1 | 5 | 1 | 3 | 8 | 0 | 1 | 4 | 2 | 5 | 2 | 0 | 3 | 5 | 0 | 6 | 1 | 0 | 5 | 5 | 0 | 0 | 0 | 0 |
,| Dasatinib 70 mg + Lenalidomide 15 mg + Dexamethasone 40 mg | 0 | 1 | 2 | 0 | 0 | 3 | 0 | 2 | 3 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 4 | 1 | 0 | 0 | 1 | 0 |
,| Dasatinib 70 mg + Lenalidomide 20 mg + Dexamethasone 40 mg | 2 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Number of Patients With Organ Response
"Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.~Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%." (NCT00564889)
Timeframe: Duration of study (up to 3 years)
| Intervention | participants (Number) |
|---|
| Len/Cyc/Dex | 11 |
Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
"Response that was confirmed on 2 consecutive evaluations during treatment.~Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.~Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.~Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels." (NCT00564889)
Timeframe: Duration on study (up to 3 years)
| Intervention | participants (Number) |
|---|
| Len/Cyc/Dex | 21 |
Number of Participants With Severe Adverse Events
Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. (NCT00564889)
Timeframe: Duration of study (up to 3 years)
| Intervention | participants (Number) |
|---|
| Len/Cyc/Dex | 26 |
Overall Survival (OS)
Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method. (NCT00564889)
Timeframe: Duration of study (up to 3 years)
| Intervention | months (Median) |
|---|
| Len/Cyc/Dex | 37.8 |
Progression Free Survival (PFS)
Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method. (NCT00564889)
Timeframe: Duration of study (up to 3 years)
| Intervention | months (Median) |
|---|
| Len/Cyc/Dex | 28.3 |
Final Response Rate After 4 Courses of Treatment
(NCT00567229)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Stable Disease (SD) | Progression of Disease (POD) |
|---|
| Lenalidomide and Rituximab | 2 | 1 |
Overall Response Rate in Patients Without Del(11q22.3)
Percentage of non-del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions. (NCT00602459)
Timeframe: Up to 15 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A (Rituximab, Fludarabine Phosphate) | 75 |
| Arm B (Rituximab, Fludarabine Phosphate, Lenalidomide) | 69 |
| Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) | 71 |
Overall Response Rates in Patients With Del(11q22.3)
Percentage of del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions. (NCT00602459)
Timeframe: Up to 15 years
| Intervention | percentage of participants (Number) |
|---|
| Arm C (Rituximab, Fludarabine Phosphate, Cyclophosphamide) | 59 |
| Arm D (Rituximab, Fludarabine, Cyclophosphamide, Lenalidomide) | 74 |
PFS Rate of Patients With Del(11q22.3)
Proportion of del (11q22.3) participants who were alive and progression free at 2 years. (NCT00602459)
Timeframe: 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm C2, FCR in Del(11q22.3) | 0.56 |
| Arm D, FCR+L in Del(11q22.3) | 0.65 |
Time-to-progression in Patients With Del(11q22.3)
Time to progression (TTP) in del(11q22.3) participants was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. (NCT00602459)
Timeframe: Up to 15 years
| Intervention | months (Median) |
|---|
| Arm C2, FCR in Del(11q22.3) | 35.5 |
| Arm D, FCR+L in Del(11q22.3) | 44.6 |
Time-to-progression in Patients Without Del(11q22.3)
Time to progression (TTP) was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progressive disease (PD) required at least one of the following: >= 50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes, >= 50% increase in the product of at least two lymphnodes, >= 50% increase in the enlargement of the liver and/or spleen. (NCT00602459)
Timeframe: Up to 15 years
| Intervention | months (Median) |
|---|
| Arm A, FR in Non-del(11q22.3) | 43.5 |
| Arm B, FR+L in Non-del(11q22.3) | 66.0 |
| Arm C1, FCR in Non-del(11q22.3) | 78.0 |
2-Year Progression Free Survival (PFS) Rate
Proportion of participants who were alive and progression free at 2 years. (NCT00602459)
Timeframe: 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A, FR in Non-del(11q22.3) | 0.64 |
| Arm B, FR+L in Non-del(11q22.3) | 0.71 |
| Arm C1, FCR in Non-del(11q22.3) | 0.74 |
Change in Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) Score From Baseline to Cycle 12
A combined scale was used to assess the quality of life (QOL) comprising of the well established and validated functional well-being (FWB) and physical well-being (PWB) components of FACT-G version 4 (14 questions), which will address the physical and functional well-being of multiple myeloma patients plus the FACT-neurotoxicity (NTX, 11 questions), which will evaluate symptoms of neurotoxicity. This pooled scale is referred to as the FACT Ntx TOI. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible outcome) to 100 (best possible outcome). (NCT00602641)
Timeframe: Administered at registration, the beginning of cycle 7 d1, the end of cycle 12 d28, then at the end of cycle 18, 24, and 38 d28. For patients who discontinue treatment early, assessed at time of discontinuation and at the next quarterly follow-up visit.
| Intervention | units on a scale (Mean) |
|---|
| Arm I (MPT-T) | -2.8 |
| Arm II (mPR-R) | 3.3 |
Overall Survival
Overall survival was defined as time from randomization to death from any cause. (NCT00602641)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 10 years from the date of randomization.
| Intervention | months (Median) |
|---|
| Arm I (MPT-T) | 52.6 |
| Arm II (mPR-R) | 47.7 |
Very Good Partial Response (VGPR) Rate
Response evaluation was based on the International Myeloma Working Group (IMWG) response criteria. VGPR rate was defined as patients achieving at least VGPR which include patients who achieving complete response (CR) and VGPR. CR refers to patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow. VGPR refers to patients who meet the following criteria: Serum and urine M-component detectable by immunofixation but not on electrophoresis; Or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 hours; If the serum and urine M protein are unmeasurable and the immunoglobulin free light chain parameter is being used to measure response, a ≥ 90% decrease in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M protein criteria. (NCT00602641)
Timeframe: Assessed every cycle (1 cycle=28 days) for the first 12 cycles, and then every 2 cycles while on treatment. Post treatment assessed every 3 months < 2 years from study entry, every 6 months if 2-5 years, every 12 months if 6-10 years from study entry.
| Intervention | proportion of participants (Number) |
|---|
| Arm I (MPT-T) | 0.247 |
| Arm II (mPR-R) | 0.316 |
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the earlier of progression or death of any cause. (NCT00602641)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 10 years from the date of randomization.
| Intervention | months (Median) |
|---|
| Arm I (MPT-T) | 21.0 |
| Arm II (mPR-R) | 18.7 |
Overall Survival (OS)
Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method. (NCT00602836)
Timeframe: time from registration to death (up to 5 years)
| Intervention | months (Median) |
|---|
| PCR-Lenalidomide | NA |
Treatment Free Survival (TFS)
Treatment Free Survival (TFS) was defined as the time from registration to the earliest date documentation of subsequent treatment or death, whichever came first. Participants were followed for a maximum of 5 years from registration. The median TFS with 95% CI was estimated using the Kaplan Meier method. (NCT00602836)
Timeframe: time from registration to progression (up to 5 years)
| Intervention | months (Median) |
|---|
| PCR-Lenalidomide | NA |
Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide
MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD. (NCT00602836)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| PCR-Lenalidomide | 4 |
Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide
"According to the NCIWG criteria, response is defined as follows:~nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above" (NCT00602836)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| PCR-Lenalidomide | 5 |
Number of Participants With a Response (CR, nPR, PR)
Response criteria described in above outcomes. (NCT00602836)
Timeframe: During treatment (up to 5 years)
| Intervention | Participants (Count of Participants) |
|---|
| PCR-Lenalidomide | 38 |
Number of Participants With Complete Response (CR)
"A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months:~- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate & biopsy" (NCT00602836)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|
| PCR-Lenalidomide | 14 |
Number of Participants With Dose-limiting Toxicities
"Dose-limiting toxicity was defined as any of the following events assessed as related to carfilzomib, lenalidomide, or dexamethasone: Nonhematologic~≥ Grade 2 neuropathy with pain~≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia due to dexamethasone, and rash due to lenalidomide)~≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal supportive therapy~≥ Grade 4 fatigue persisting > 7 days~Treatment delay for toxicity > 21 days~Hematologic~Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) > 7 days~Febrile neutropenia (ANC < 1,000/mm³ with fever ≥ 38.3ºC)~Grade 4 thrombocytopenia (platelets < 25,000/mm³) for > 7 days despite holding treatment, or Grade 3 or 4 thrombocytopenia associated with bleeding~Treatment delay for toxicity > 21 days.~The maximum-tolerated dose was defined as the dose level below which a drug-related DLT was observed in ≥ 33% of participants in a cohort." (NCT00603447)
Timeframe: Cycle 1, 28 days
| Intervention | participants (Number) |
|---|
| 1: CFZ 15 mg/m² + LEN 10 mg | 0 |
| 2: CFZ 15 mg/m² + LEN 15 mg | 0 |
| 3: CFZ 15 mg/m² + LEN 20 mg | 0 |
| 4: CFZ 20 mg/m² + LEN 20 mg | 0 |
| 5: CFZ 20 mg/m² + LEN 25 mg | 0 |
| 6: CFZ 20/27 mg/m² + LEN 25 mg | 1 |
Number of Participants With Adverse Events (AEs)
"Treatment-related are those AEs with possible or probable relationship to carfilzomib, lenalidomide or dexamethasone as assessed by the Investigator. The severity of each adverse event was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, per the following: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.~Serious adverse events were defined as AEs meeting one of the following: death, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in the offspring of an exposed participant, important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above, or pregnancy or suspected pregnancy." (NCT00603447)
Timeframe: From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.
| Intervention | participants (Number) |
|---|
| Any adverse event | Treatment-related adverse event | Grade 3 or higher adverse event | Treatment-related Grade 3 or higher adverse event | Serious adverse event | AE leading to discontinuation of any study drug | AE leading to discontinuation of carfilzomib | Deaths within 30 days of last dose of study drug |
|---|
| 1: CFZ 15 mg/m² + LEN 10 mg | 6 | 4 | 5 | 1 | 3 | 1 | 0 | 0 |
,| 2: CFZ 15 mg/m² + LEN 15 mg | 6 | 5 | 6 | 4 | 3 | 1 | 0 | 0 |
,| 3: CFZ 15 mg/m² + LEN 20 mg | 8 | 8 | 8 | 7 | 4 | 3 | 1 | 0 |
,| 4: CFZ 20 mg/m² + LEN 20 mg | 6 | 4 | 6 | 4 | 4 | 4 | 2 | 0 |
,| 5: CFZ 20 mg/m² + LEN 25 mg | 6 | 6 | 6 | 6 | 3 | 2 | 1 | 0 |
,| 6: CFZ 20/27 mg/m² + LEN 25 mg | 8 | 8 | 8 | 8 | 6 | 3 | 1 | 0 |
,| 7: CFZ 20/27 mg/m² + LEN 25 mg | 44 | 43 | 41 | 38 | 22 | 18 | 9 | 3 |
Clinical Benefit Rate
The ORR rate plus Stable Disease (SD). NCI-WG: SD is the absence of progressive disease (PD) and failure to achieve at least a PR; PD: at least one of the criteria of Group A or Group B has to be met. (NCT00609869)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Lenalidomide and Rituximab | 83.3 |
Overall Response Rate (ORR)
The sum of Complete Remission (CR) plus Partial Remission (PR) rates. Duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, and must be confirmed greater than 8 weeks after first meeting CR or PR criteria. Response and progression for Chronic Lymphocytic Leukemia (CLL) were evaluated using 2008 updated National Cancer Institute-Sponsored Working Group Guidelines (NCI-WG) for Chronic Lymphocytic Leukemia. CR: all of the criteria must be met, and patients have the lack disease-related constitutional symptoms: PR: at least two of the criteria of Group A plus one of the criteria of group B have to be met. Group A Parameters: Lymphadenopathy; Hepatomegaly; Splenomegaly; Blood; Lymphocytes; Marrow. Group B Parameters: Platelet count; Hemoglobin; Neutrophils. (NCT00609869)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Lenalidomide and Rituximab | 61 |
Overall Response Rate (ORR) - Percentage of Participants With Partial Response or Better With Induction Regimen
ORR assessed using International Myeloma Working Group Response Definitions. Partial Remission (PR): A greater than 50% reduction in the serum paraprotein, and if present, a greater than 90% reduction in the urine M protein excretion. Patients must also have a decrease by 50% in the size of soft tissue plasmacytoma. If serum and urine M protein are not measurable, a 50% or greater decreased in the difference of the involved and uninvolved free light chain. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared. (NCT00617591)
Timeframe: 24 Months
| Intervention | percentage of participants (Number) |
|---|
| Induction and Maintenance Therapy | 77.2 |
Percentage of Participants With Very Good Partial Remission (VGPR) or Better
Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction Dd-R as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared. (NCT00617591)
Timeframe: 24 Months
| Intervention | percentage of participants (Number) |
|---|
| Induction and Maintenance Therapy | 42.1 |
Occurrence of Induction Toxicities
"Tolerability of full dose Revlimid® with full dose Doxil® in combination with reduced schedule dexamethasone was to be assessed during Cycle 1 and at the start of Cycle 2 using, whenever possible, the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0.~Due to increased neutropenia and fatigue, toxicities were reviewed after the first 29 participants were enrolled." (NCT00617591)
Timeframe: 24 Months
| Intervention | percentage of participants (Number) |
|---|
| Percentage with Dose Reductions Required | Percentage Receiving < 4 Cycles of Therapy | Percentage Who Discontinued After Only 1 Cycle | Percentage with Grade 3/4 Neutropenia | Percentage with Grade 3/4 Fatigue |
|---|
| Induction at Initial Full Dose | 24 | 20 | 13.79 | 48 | 20 |
2 Year Overall Survival (OS) Rate
Percentage of participants with Overall Survival in response to Dd-R in newly diagnosed multiple myeloma patients with active disease. Overall survival is time from study entry to death of any cause. (NCT00617591)
Timeframe: 24 Months
| Intervention | percentage of participants (Number) |
|---|
| Induction and Maintenance Therapy | 79.6 |
Number of Patients Who Experience Improvement in GVHD on Lenalidomide, Defined as the Reduction in Severity of GVHD as Defined by the National Institutes of Health (NIH) Consensus Criteria
(NCT00619684)
Timeframe: Up to 9 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide) | 0 |
Response Rate, Defined as the Number of Patients Achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR)
"CR: No Monoclonal Protein (MP) in the blood AND no serum/urine MP by Immunofixation (IF < 0) AND < 5% plasma cells in bone marrow aspirate.~VGPR: More than 90% decrease of MP and urine M protein < 100 mg/d OR serum protein electrophoresis (SPEP)/urine protein electrophoresis(UPEP) negative but serum immunofixation (IFs) or IFu urine immunofixation (IFu) ) still positive.~PR: Over 50% decrease of serum MP AND > 90% reduction in 24h urinary light chain excretion or M proteinuria < 200mg/d MR: Between 25 and 49% decrease of MP in the blood AND 50-89% reduction in 24h urinary light chain excretion (monoclonal proteinuria>200 mg/d)" (NCT00619684)
Timeframe: Up to 9 years
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Very Good Partial Response (VGPR) | Partial Response (PR) | Minimal Response (MR) |
|---|
| Treatment (Lenalidomide) | 5 | 2 | 3 | 1 |
Overall Survival
Kaplan-Meier estimate of survival (NCT00619684)
Timeframe: At 1 and 2 years after starting treatment with lenalidomide
| Intervention | percentage of participants (Number) |
|---|
| Percent Overall Survival at 1 year | Percent Overall Survival at 2 years |
|---|
| Treatment (Lenalidomide) | 71 | 58 |
Adverse Events, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Grade 1-2 adverse events occurring in >10% of participants. Grade 3 or higher adverse events occurring in one or more participants. (NCT00619684)
Timeframe: Up to 30 days after completion of study treatment
| Intervention | percentage of participants (Number) |
|---|
| Grade 1-2 constipation | Grade 1-2 diarrhea | Grade 1-2 fatigue | Grade 1-2 myalgia | Grade 1-2 nausea | Grade 1-2 neuropathy | Grade 1-2 thrombocytopenia | Grade 3 pneumonia | Grade 3 H1N1 influenza | Grade 3 fever, hypoxia and neuropathy | Grade 3 myalgia | Grade 3 neuropathy | Grade 3 neutropenia |
|---|
| Treatment (Lenalidomide) | 28 | 17 | 17 | 17 | 11 | 11 | 11 | 17 | 11 | 6 | 6 | 6 | 44 |
TTP
"Time to Progression (TTP): Time from start of therapy to meeting the definition of Progressive Disease (PD).~PD: 25% increase compared to the lowest value of:~Serum MP (absolute increase at least ≥ 0.5 g/dl)~Or: Urine MP (absolute increase at least > 200 mg/24h)~Or: for patients without measurable MP, Serum Free Light Chain test: the difference between involved and uninvolved FLC levels (absolute increase at least >100 mg/L)" (NCT00619684)
Timeframe: Up to 9 years
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide) | 8.5 |
Number of Patients Requiring Dose Interruption, Dose Reduction or Discontinuance of Lenalidomide
Dose interruption, dose reduction or discontinuation of lenalidomide due to toxicity, GVHD or disease progression (NCT00619684)
Timeframe: Up to 9 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide) | 13 |
Number of Participants With Adverse Events (AE) During the Extension Phase
An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; (NCT00622336)
Timeframe: From 22 Oct 2009 to November 2013; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit.
| Intervention | participants (Number) |
|---|
| ≥ 1 Adverse Event (AE) | Adverse Event related to study drug | Adverse Event NCI CTC (Version2.0) Grade 3 or 4 | ≥ 1 Serious Adverse Event (SAE) | ≥ 1 AE leading to discontinuation of study drug | ≥ 1 AE leading to dose reduction/interruption |
|---|
| Lenalidomide 25mg (CC-5013) | 13 | 1 | 5 | 5 | 1 | 3 |
Number of Participants With Adverse Events (AE) During the Treatment Phase
An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; (NCT00622336)
Timeframe: Until data cut-off of 22 Oct 2009; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. Maximum exposure to Lenalidomide treatment was 1260 days.
| Intervention | participants (Number) |
|---|
| Adverse Event (AE) | Adverse Event related to study drug | Adverse Event NCI CTC (Version2.0) Grade 3 or 4 | Serious Adverse Event (SAE) | AE leading to discontinuation of study drug | AE leading to dose reduction/interruption |
|---|
| Lenalidomide 25mg (CC-5013) | 327 | 268 | 256 | 177 | 52 | 210 |
Time to Progression
Time from the start of study drug therapy to the first documentation of disease progression. Progressive disease characterized by at least one of the following: >50% increase in the sum of products of at least 2 lymph nodes on 2 consecutive examinations. At least one node larger than 2 cm. Or, appearance of new enlarged lymph nodes. >50% increase in size of liver and/or spleen as determined by physical examination or appearance of splenomegaly which was not previously present. >50% increase in number of circulating lymphocytes with absolute count of at least 10,000. (NCT00632359)
Timeframe: From baseline to 12 months
| Intervention | Months (Mean) |
|---|
| Lenalidomide | 8 |
Response Assessments: Disease Status at the End of Lenalidomide Consolidation Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Response Criteria
Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; positive or negative minimal residual disease (MRD); Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts; Nodular Partial Remission (nPR) is CR with bone marrow nodules identified histologically. Progressive disease (PD), defined as ≥ 50% rise in lymphocyte count to > 5 x109/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL; Stable disease, defined as not meeting criteria for CR, PR or PD. (NCT00632359)
Timeframe: 12 Months, Disease status assessed at the End of Lenalidomide Consolidation
| Intervention | participants (Number) |
|---|
| CR, MRD Positive or Negative | PR | nPR | PD |
|---|
| Assessment at End of Consolidation | 13 | 8 | 7 | 1 |
Improvement in Quality of Remission: Number of Participants With Response Versus No Response by NCI Working Group Criteria Disease Status Change at Start/End of Lenalidomide Consolidation
To evaluate ability of lenalidomide to improve quality of remission (e.g. from partial remission (PR) to complete remission (CR)), disease status assessed at start & end of Lenalidomide consolidation. NCI Working Group Response Criteria: Participants who began therapy in PR, improvement of status to nodular partial remission (nPR) or CR; Participants in nPR (otherwise CR, bone marrow nodules identified histologically), improvement of status to CR. Participants in CR, resolution of measurable disease in blood &/or bone marrow per immuno flow cytometry or PCR testing. Progressive Disease (PD): One or more of following: >50% increase in sum of products of =/>2 lymph nodes on 2 consecutive examinations; One+ node must be >2 cm or appearance of new enlarged lymph nodes; >50% increase in liver &/or spleen as determined by physical examination/appearance of splenomegaly not previously present; >50% increase in circulating lymphocytes with absolute count >10,000. (NCT00632359)
Timeframe: Baseline to 12 Months, Disease status assessed at Start/End of Lenalidomide Consolidation
| Intervention | participants (Number) |
|---|
| Response | No Response |
|---|
| Lenalidomide | 10 | 21 |
Incidence of Non-Serious Adverse Events as a Measure of Safety and Tolerability, Phase II
"A count of affected participants with non-serious adverse events (regardless of relationship to study treatments) occurring in >= 15% of treated patients enrolled in the Phase II section of the study.~Lenalidomide DL-1 dose (10 mg orally, once daily (PO QD)) Day 1-14 followed by 7 days of rest, Rituximab 375 mg/m2 IV Days 1, 8, and 15 of Cycle 1; Cycles 2-6: 375 mg/m2 IV Day 1, Bortezomib 1.3 mg/m2 subcutaneous Days 1, 4, 8, and 11 for Cycles 1-6" (NCT00633594)
Timeframe: Collected from day of first dose to 30 days after the last dose of study medication, a maximum of 18 weeks and 30 days after last study treatment
| Intervention | participants (Number) |
|---|
| Rash | Fatigue | Thrombocytopenia | Leukopenia | Nausea | Diarrhea | Edema | Hyperglycemia | Peripheral Neuropathy | Neutropenia | Hypoalbuminemia | Constipation | Hypocalcemia | Pain in Extremity | Anemia | Cough | Fever | Dehydration | Pruritus | Dyspnea | Hyponatremia | Insomnia | Abdominal Pain | Dizziness | Hypokalemia | Weight Loss | Anorexia | Erythema | Hypomagnesemia | Allergic Reaction | Chills | Hyperhidrosis | Myalgia | Headache | Mucositis | Hypoglycemia |
|---|
| Phase II - Lenalidomide 10mg PO QD | 19 | 18 | 16 | 13 | 12 | 11 | 11 | 11 | 10 | 10 | 10 | 9 | 9 | 9 | 8 | 8 | 8 | 7 | 7 | 7 | 7 | 6 | 6 | 6 | 6 | 6 | 5 | 5 | 5 | 5 | 5 | 5 | 4 | 4 | 4 | 4 |
Duration of Response (DoR) of Phase I and Phase II Participants
"Measured from the documented beginning of response (CR or PR) to the time of relapse. This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement.~Duration of Response will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification." (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years or until documented disease progression
| Intervention | months (Median) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 25.72 |
| Phase II Participants (10 mg Lenalidomide) | 17.81 |
Duration of Response (DoR) of Previously Treated and Previously Untreated Participants
Measured from the documented beginning of response (CR or PR) to the time of relapse. This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement. (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years or until documented disease progression
| Intervention | months (Median) |
|---|
| Previously Treated Participants | 17.94 |
| Previously Untreated Participants | 21.09 |
Maximum Tolerated Dose of Lenalidomide Combined With Bortezomib and Rituximab in Phase I Participants
"Determination of the maximum tolerated dose (MTD) of lenalidomide combined with bortezomib and rituximab, defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity according to the NCI CTCAE v. 4.03.~MTD of Lenalidomide was tested, included with 1.3 mg/m2 subcutaneous (D1, 4, 8, 11) bortezomib, 375 mg/m2 (D1, 8, 15 of Cycle 1, D1 on subsequent cycles) rituximab.~Three dose limiting toxicities were reported in two patients (grade 4 neutropenia and grade 3 neuropathy, grade 3 rash)" (NCT00633594)
Timeframe: Collected from day of first dose to the end of the first treatment cycle, up to 21 days
| Intervention | mg lenalidomide, orally, daily, day 1-14 (Number) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 10 |
Overall Response Rate (ORR) of Phase I and Phase II Participants
Response to treatment (Complete Response (CR) or Partial Response (PR)) determined using Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses, no increase in the size of other nodes, liver or spleen, no new sites of disease, patients who achieve CR but have persistent morphologic bone marrow involvement; Stable Disease (SD): failing to attain PR or CR, but not fulfilling criteria for progressive disease; Progressive Disease (PD)/Relapse: appearance of new lesions more than 1.5 cm in any axis, 50% or greater increase from nadir SPD of any previously involved sites, 50% or greater increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in short axis. (NCT00633594)
Timeframe: Every 6 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 12 |
| Phase II Participants (10 mg Lenalidomide) | 21 |
Overall Response Rate (ORR) of Previously Treated and Previously Untreated Participants
Response to treatment (Complete Response (CR) or Partial Response (PR)) determined using Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses, no increase in the size of other nodes, liver or spleen, no new sites of disease, patients who achieve CR but have persistent morphologic bone marrow involvement; Stable Disease (SD): failing to attain PR or CR, but not fulfilling criteria for progressive disease; Progressive Disease (PD)/Relapse: appearance of new lesions more than 1.5 cm in any axis, 50% or greater increase from nadir SPD of any previously involved sites, 50% or greater increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in short axis. (NCT00633594)
Timeframe: Every 6 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Previously Treated Participants | 8 |
| Previously Untreated Participants | 25 |
Overall Survival of Phase I and Phase II Participants
"Defined as the date of study entry to the date of death.~Overall Survival will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification" (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years, then every 6 months after documented disease progression
| Intervention | months (Median) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 51.45 |
| Phase II Participants (10 mg Lenalidomide) | 35.35 |
Overall Survival of Previously Treated and Previously Untreated Participants
"Defined as the date of study entry to the date of death.~Overall Survival will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification" (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years, then every 6 months after documented disease progression
| Intervention | months (Median) |
|---|
| Previously Treated Participants | 28.4189 |
| Previously Untreated Participants | 71.2608 |
Time to Best Response of Previously Treated and Previously Untreated Participants
Measured from the time of study entry to the documented beginning of response (CR or PR). This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement. (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years
| Intervention | months (Median) |
|---|
| Previously Treated Participants | 2.04 |
| Previously Untreated Participants | 2.37 |
Progression Free Survival (PFS) of Previously Treated and Previously Untreated Participants
"Defined as the time from entry onto study until lymphoma progression or death from any cause.~Progression Free Survival will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification." (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years, then every 6 months after documented disease progression
| Intervention | months (Median) |
|---|
| Previously Treated Participants | 12.4517 |
| Previously Untreated Participants | 25.2649 |
Time to Best Response of Phase I and Phase II Participants
"Measured from the time of study entry to the documented beginning of response (CR or PR). This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement.~Time to Best Response will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification." (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years
| Intervention | days (Median) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 63.50 |
| Phase II Participants (10 mg Lenalidomide) | 71.50 |
Progression Free Survival (PFS) of Phase I and Phase II Participants
"Defined as the time from entry onto study until lymphoma progression or death from any cause.~Progression Free Survival will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification." (NCT00633594)
Timeframe: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years, then every 6 months after documented disease progression
| Intervention | months (Median) |
|---|
| Phase I Participants (10 mg/15 mg Lenalidomide) | 27.70 |
| Phase II Participants (10 mg Lenalidomide) | 19.35 |
Skindex Function
"Skindex function scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of function impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of function on QoL is 100. This is represented as a 5 on the 1-5 scale." (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 41.26 | 30.42 | 29.2 | 4.2 |
Patient General Assessment (PtGA) for Skin
General skin scores were recorded by the patient on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 5.6 | 3.6 | 4.2 | 0.8 |
Pain in Skin
Pain in skin was recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no pain and 10 to pain as bad as you can imagine. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 4.5 | 2 | 2.5 | 0.5 |
Number of Participants With Change in IFN and CD4 Levels at 6 Weeks
CXCL10, an interferon-inducible chemokine, and immunophenotyping by immunostaining. Measurement of interferon-inducible genes from peripheral blood mononuclear cells before and after treatment. (NCT00633945)
Timeframe: 6 weeks
| Intervention | Participants (Count of Participants) |
|---|
| IFN score decrease | CD4 decrease |
|---|
| Lenalidomide Nonresponder | 1 | 1 |
,| Lenalidomide Responders | 4 | 4 |
Fatigue
Fatigue scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no fatigure and 10 to fatigue as bad as you can imagine. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 7.25 | 3.4 | 5.25 | 3 |
Cutaneous Lupus Area and Severity Index (CLASI)
The Cutaneous Lupus Area and Severity Index (CLASI); range of disease activity is 0-70. Lower scores reflect less activity. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| 0 weeks | 6 weeks | 12 weeks | 52 weeks |
|---|
| Lenalidomide | 21.4 | 10.8 | 8.6 | 5.3 |
Itch in Skin
Itch scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no itch and 10 to itch as bad as you can imagine. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 4.0 | 1.2 | 2.25 | 0 |
Skindex Symptoms
"Skindex symptoms scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of symptom impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of symptoms on QoL is 100. This is represented as a 5 on the 1-5 scale." (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 58.5 | 41.82 | 36.4 | 12.5 |
Physician Global Assessment (PGA) for Skin
General skin scores were recorded on a 10 cm visual analogue scale at each visit. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health. (NCT00633945)
Timeframe: Weeks 0 through 52
| Intervention | units on a scale (Mean) |
|---|
| week 0 | week 6 | week 12 | week 52 |
|---|
| Lenalidomide | 6 | 3 | 3.8 | 2 |
Number of Participants Experiencing Best Overall Response Determined by Complete Response (CR), Near Complete Response (NCR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)
Best overall tumor response consisted of CR (negative M-protein immunofixation [IF], <5% bone marrow [BM] plasma cells, no soft tissue plasmacytomas [STP]), NCR (positive M-protein IF, <5% BM plasma cells, no STP), VGPR (≥90% M-protein decrease, <5% BM plasma cells, no STP), PR (≥50% M-protein, BM plasma cells, STP decrease), MR (25-49% M-protein, BM plasma cells, STP decrease), SD (<25% decrease-25% increase in M-protein, BM plasma cells; <25% decrease-increase in definite STP) or PD (≥25% M-protein, BM plasma cells increase; new STP, lesions). Per protocol participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD were analyzed as a single prespecified analysis at the time of protocol-specified final statistical analysis with a 3-Sep-2012 data cut-off. The number of participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD is reported here for all participants who got ≥1 dose of study drug and had a post baseline efficacy assessment. (NCT00642954)
Timeframe: Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)
| Intervention | Participants (Count of Participants) |
|---|
| CR | NCR | VGPR | PR | MR | SD | PD |
|---|
| Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | 0 | 0 | 1 | 1 | 0 | 1 | 1 |
,| Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | 0 | 1 | 0 | 1 | 0 | 1 | 1 |
,| Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
,| Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
,| Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | 1 | 0 | 2 | 5 | 2 | 5 | 1 |
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting <48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug. (NCT00642954)
Timeframe: Cycle 1 (Up to 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | 0 |
| Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | 0 |
| Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | 0 |
| Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | 0 |
| Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | 1 |
Response Rates ()
The response rate was calculated as the number of patients with documented confirmed partial response (PR) or better, which includes confirmed/unconfirmed stringent complete response (sCR), confirmed/unconfirmed complete response (CR), confirmed/unconfirmed very good partial response (VGPR), or confirmed partial response (PR), as best response divided by the total number of evaluable patients, in each arm. Patients with measurable disease, as defined in the protocol, are evaluable. Response rates were compared between the two treatment arms using a stratified Cochran-Mantel-Haenszel test. Response designations were based on the International Uniform Response Criteria for Multiple Myeloma. Due to the complexity of these criteria, the details of these criteria have been omitted. (NCT00644228)
Timeframe: Up to 6 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Dexamethasone and Lenalidomide) | 153 |
| Arm II (Dexamethasone, Lenalidomide, Bortezomib) | 176 |
Progression-free Survival
Unstratified median progression-free survival in months. (NCT00644228)
Timeframe: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 6 years
| Intervention | Months (Median) |
|---|
| Arm I (Dexamethasone and Lenalidomide) | 30 |
| Arm II (Dexamethasone, Lenalidomide, Bortezomib) | 43 |
Overall Survival
Unstratified median overall survival in months. (NCT00644228)
Timeframe: Up to 6 years
| Intervention | Months (Median) |
|---|
| Arm I (Dexamethasone and Lenalidomide) | 64 |
| Arm II (Dexamethasone, Lenalidomide, Bortezomib) | 75 |
Number of Participants With Overall Clinical Benefit (OCB), Defined as the Sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Divided by the Number of Participants
"The OCB was assessed using Recist 1.0 as defined in the protocol. A CR was defined as the disappearance of all lesions. A PR was defined as > or equal to a 30% decrease in the sum of the longest diameter of measureable lesions, SD was defined < a 30% decrease in the sum of the longest diameter of measureable lesions and < a 20% increase in the sum of the longest diameter of measureable lesions. For a CR, PR or SD, there are no new lesions.~Prostate-Specific Antigen (PSA) was also evaluated. A PSA CR was a PSA < or equal to 4 ng/dl. A PSA PR was a PSA that decreased by > or equal to 50%. Stable PSA was defined as a PSA that increased >25% and decreased < 50%." (NCT00654186)
Timeframe: 24 months for acrual
| Intervention | percentage of patients (Number) |
|---|
| Revlimid Oral for 21days | 74 |
Time to PSA Progression
As defined in the protocol PSA progression was an increase of at least 25% (NCT00654186)
Timeframe: 24 months for acrual
| Intervention | months (Median) |
|---|
| Revlimid Oral for 21days | 3 |
Time to Disesase Progression as Measured by Radiographic Progression
Progressive disease (PD) was determined, as outlined in the protocol, by using Recist 1.0. PD is defined as greater than or equal to a 20% increase in the sum of all measureable lesions or the apprearance of two new bone lesions or the appearnce of one new soft tissue lesion. (NCT00654186)
Timeframe: 24 months
| Intervention | months (Median) |
|---|
| Revlimid Oral for 21days | 4 |
Progression-Free Survival
Kaplan-Meier estimate of progression-free survival is defined as the start of study drug therapy to the first observation of disease progression or death due to any cause. (NCT00655668)
Timeframe: Up to 24 months
| Intervention | Months (Median) |
|---|
| Single Agent Lenalidomide | 2.53 |
Duration of Response
Kaplan-Meier Estimate of duration of response calculated as the time from first computed tomography (CT) Scan or magnetic resonance imaging (MRI) that demonstrates at least a partial response to the first documentation of disease progression, including death due to Non-Hodgkin's Lymphoma. (NCT00655668)
Timeframe: Up to 24 months
| Intervention | Months (Median) |
|---|
| Single Agent Lenalidomide | 3.55 |
Participants Categorized by Best Response as Determined by Investigator
"Participant response assessed by investigator; criteria by B. Cheson in Journal of Clinical Oncology, 1999 (see article for more detail):~Complete Response(CR): Complete disappearance of all detectable disease~Complete Response Unconfirmed(CRu): CR, but indeterminate bone marrow~Partial Response(PR): >50% decrease in six largest nodes/nodal masses~Stable Disease(SD): Less than PR, but not progressive disease~Relapsed Disease: In CR/CRu Patients, new lesions seen or increased by >=50% in previous sites~Progressive Disease(PD): >=50% increase from low in PR/Non-Responders" (NCT00655668)
Timeframe: Up to 24 months
| Intervention | Participants (Number) |
|---|
| Complete Response (CR) | Complete Response Unconfirmed (CRu) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | No Response Assessment | Other | Tumor Control (CR+CRu+PR+SD) |
|---|
| Single Agent Lenalidomide | 4 | 2 | 6 | 16 | 16 | 9 | 1 | 28 |
Safety
Summary of Treatment-Emergent Events in Safety Population (participants with at least one dose of study drug). Events assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 3: Following is the scale: Grade 1=Mild Adverse Event (AE), Grade 2=Moderate AE, Grade 3=Severe and Undesirable AE, Grade 4=Life-threatening or Disabling AE, and Grade 5=Death Related to AE.) (NCT00655668)
Timeframe: Up to 24 months
| Intervention | Participants (Number) |
|---|
| At least 1 adverse event (AE) | At least 1 AE related to drug | At least 1 NCI CTCAE Grade 3-4 AE | At least 1 NCI CTCAE Gr 3-4 AE related to drug | At least 1 serious adverse event (SAE) | At least 1 SAE related to drug | At least 1 AE leading to drug withdrawal (WD) | At least 1 AE leading to drug interruption/WD |
|---|
| Single Agent Lenalidomide | 53 | 40 | 34 | 19 | 29 | 16 | 21 | 19 |
Change in Total Neuropathy Score in Subjects With MGUS Associated Neuropathy After Treatment With Lenalidomide.
"Minimum value of the Total Neuropathy Score is 0, maximum value is 40. A higher score represents a worsening." (NCT00665652)
Timeframe: Baseline, 12 months
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 0.17 |
Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)
Other Phase II Cohorts were not evaluable for event-free survival analysis. (NCT00670358)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Ph II, DLBCL/Mixed | 44 |
Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)
(NCT00670358)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3+ Adverse Event | Grade 4+ Adverse Event | Grade 3+ Hem Adverse Event | Grade 4+ Hem Adverse Event | Grade 3+ Non-Hem Adverse Event |
|---|
| Ph 1, DL 1 | 3 | 2 | 3 | 2 | 1 |
,| Ph1, DL 2 | 3 | 1 | 3 | 1 | 1 |
,| Ph1, DL 3 | 5 | 4 | 5 | 4 | 2 |
Number of Participants' With Treatment Response of Complete or Partial Response
Treatment responses defined as complete (CR) or partial organ response (PR) of chronic Graft-Versus-Host Disease (GVHD) to lenalidomide. Complete organ response (CR) indicates resolution of all reversible manifestations related to chronic GVHD in a specific organ. Partial organ response (PR) requires at least 50% improvement in scale used to measure disease manifestations related to chronic GVHD. Tools for response evaluation were skin assessment and functional assessment including minute walk and grip strength. (NCT00675441)
Timeframe: Response assessed after completing 28 day cycle, repeated with each cycle for 6 cycles, approximately 180 days.
| Intervention | participants (Number) |
|---|
| Lenalidomide | 2 |
Number of Participants With Hematologic Response
"Complete hematologic response: Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, bone marrow biopsy with less than 5% plasma cells without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay.~Partial hematologic response: Amyloid patients have highly individualized measures of disease burden. For patients with detectable and quantifiable monoclonal marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum or urine protein electrophoresis, a reduction in the peak height of 50% or more. For patients with quantifiable urinary kappa or lambda chain concentration, a 50% reduction in daily light chain excretion (concentration x 24 hour urine volume). For patients with an elevated serum free light chain assay, reduction of 50% or more." (NCT00679367)
Timeframe: one year
| Intervention | participants (Number) |
|---|
| Melphalan Revlimid and Dexamethasone | 7 |
Number of Participants Removed From Study Due to Toxicities
Number of study participants removed from study treatment due to toxicities (NCT00679367)
Timeframe: One year
| Intervention | Participants (Count of Participants) |
|---|
| Melphalan Revlimid and Dexamethasone | 6 |
Number of Organs Improved or Stable Based on Description Below:
"Renal response - > 50% decrease in daily 24 hour proteinuria, without worsening renal insufficiency.~Hepatic response - decrease of 2 centimeters or more of the liver span and/or decrease of the alkaline phosphatase by 50% if elevated at baseline.~Cardiac response - decrease of 2 millimeters or more in mean left ventricular wall thickness in patients with baseline wall thickness > 11 mm or a decrease in New York Heart Association heart failure class.~Autonomic nervous system response - resolution of orthostatic vital signs and symptoms, and resolution of symptoms of gastric atony or of functional ileus.~Gastrointestinal response - a greater than one grade improvement in diarrhea due to biopsy proven amyloid.~Peripheral nervous system response - resolution of clinical signs of peripheral neuropathy." (NCT00679367)
Timeframe: one year
| Intervention | number of organs stable or improved (Number) |
|---|
| Melphalan Revlimid and Dexamethasone | 10 |
Change in Cancer Pain Intensity Determined by Edmonton Symptom Assessment Scale (ESAS)
"Changes in cancer pain from baseline to day 15 using ESAS to measure participant responses to 10 common symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep problems, and feeling of well-being). Intensity of symptoms rated on a 0 to 10 scale from 0 no symptom to 10 worst possible symptom." (NCT00684242)
Timeframe: From baseline to Day 15
| Intervention | units on a scale (Number) |
|---|
| Participant 1 | Participant 2 |
|---|
| Lenalidomide | 0 | -2 |
Number of Participants With a Grade 3 and 4 Adverse Event (Phase I)
"Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.~Description of Grades:~Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death" (NCT00687674)
Timeframe: up to 3 years
| Intervention | participants (Number) |
|---|
| Sorafenib + Lenalidomide + Dexamethasone | 11 |
Change From Baseline in the EORTC QLQ-C30 Constipation Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale is scored between 0 and 100, with a high score indicating a higher level of constipation. Negative change from Baseline values indicate improvement in constipation and positive values indicate worsening of constipation. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 6.3 | 0.0 | -5.1 | -5.2 | -5.9 | -7.5 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 8.3 | 1.8 | -2.4 | -2.4 | -4.5 | -7.9 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 18.4 | 13.9 | 6.8 | 3.7 | 0.0 | -2.2 |
Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100, with a high score indicating a higher level of diarrhea. Negative change from Baseline values indicate improvement in diarrhea and positive values indicate worsening of diarrhea. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 2.3 | 3.4 | 6.0 | 9.1 | 10.9 | 6.4 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 3.8 | 3.7 | 8.2 | 11.8 | 14.8 | 10.8 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -0.6 | -2.4 | -2.2 | -2.5 | -1.7 | -0.5 |
Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT)
Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy. (NCT00689936)
Timeframe: From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 39.1 |
| Lenalidomide and Dexamethasone Rd18 | 28.5 |
| Melphalan + Prednisone + Thalidomide (MPT) | 26.7 |
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 0.1 | 3.9 | 5.8 | 4.9 | 3.1 | 3.7 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 0.6 | 3.8 | 4.6 | 4.6 | 5.8 | 2.6 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 1.0 | 2.1 | 5.5 | 5.1 | 5.1 | -0.0 |
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 4.4 | -3.4 | -5.9 | -2.3 | 0.1 | -1.6 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 2.6 | -2.5 | -3.7 | -4.3 | -3.1 | 0.3 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 2.8 | -1.8 | -4.5 | -3.9 | -4.3 | 2.7 |
Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Difficulties Scale is scored between 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicate improvement in financial difficulties and positive values indicate worsening of financial difficulties. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -0.3 | -0.4 | -0.3 | 1.6 | 1.8 | 0.5 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 2.1 | 1.9 | 1.4 | 0.4 | 2.0 | 1.9 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 0.5 | 1.9 | 0.7 | 1.1 | 0.4 | 5.0 |
Change From Baseline in the EORTC QLQ-C30 Insomnia Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 3.2 | -1.3 | -1.9 | 1.1 | 1.4 | -1.6 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 2.1 | 0.2 | -1.2 | -1.0 | -0.5 | -5.2 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -10.5 | -8.9 | -11.6 | -9.6 | -6.0 | -4.5 |
Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -0.5 | -2.5 | -4.0 | -3.6 | -2.7 | -4.2 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 1.8 | -1.1 | -1.3 | -2.2 | -2.3 | 0.4 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 4.0 | -1.2 | -3.9 | -3.9 | -3.9 | 1.0 |
Change From Baseline in the EORTC QLQ-C30 Pain Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -4.4 | -13.1 | -16.1 | -14.7 | -12.4 | -7.9 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -5.4 | -13.4 | -14.4 | -14.0 | -14.4 | -8.0 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -7.8 | -12.1 | -13.4 | -14.3 | -14.7 | -6.0 |
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -1.4 | 4.7 | 7.6 | 7.4 | 6.8 | 3.0 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -1.7 | 3.4 | 4.7 | 5.0 | 6.9 | -0.1 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -0.9 | 2.2 | 5.3 | 6.9 | 8.3 | -0.1 |
Time to First Response Based on the Review by the IRAC
The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 1.8 |
| Lenalidomide and Dexamethasone Rd18 | 1.8 |
| Melphalan + Prednisone + Thalidomide (MPT) | 2.8 |
Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 3.6 | -1.9 | -2.9 | -1.6 | 2.9 | 0.8 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 0.9 | -0.8 | -2.3 | -3.5 | -1.8 | -1.0 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 4.2 | 2.0 | 0.1 | -1.6 | 0.4 | 7.8 |
Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -2.2 | 2.0 | 5.2 | 3.8 | 3.2 | 2.7 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -4.3 | 0.7 | 4.0 | 2.9 | 4.2 | -1.2 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -1.4 | 2.4 | 3.4 | 5.8 | 6.0 | -3.5 |
Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis
Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 46.2 |
| Lenalidomide and Dexamethasone Rd18 | 53.1 |
| Melphalan + Prednisone + Thalidomide (MPT) | 45.7 |
Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review
Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 60.5 |
| Lenalidomide and Dexamethasone Rd18 | 76.8 |
| Melphalan + Prednisone + Thalidomide (MPT) | 57.5 |
Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review
Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of particpants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 80.4 |
| Lenalidomide and Dexamethasone Rd18 | 74.8 |
| Melphalan + Prednisone + Thalidomide (MPT) | 61.0 |
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis
Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 31.5 |
| Lenalidomide and Dexamethasone Rd18 | 21.5 |
| Melphalan + Prednisone + Thalidomide (MPT) | 22.1 |
Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review
Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 80.4 |
| Lenalidomide and Dexamethasone Rd18 | 81.6 |
| Melphalan + Prednisone + Thalidomide (MPT) | 70.6 |
Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review.
Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | Percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 70.0 |
| Lenalidomide and Dexamethasone Rd18 | 69.7 |
| Melphalan + Prednisone + Thalidomide (MPT) | 58.2 |
Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)
PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's). (NCT00689936)
Timeframe: From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 25.5 |
| Lenalidomide and Dexamethasone Rd18 | 20.7 |
| Melphalan + Prednisone + Thalidomide (MPT) | 21.2 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Study discontinuation |
|---|
| Lenalidomide and Dexamethasone Rd18 | -1.3 | 4.7 | 5.4 | 3.2 | 5.7 | 5.0 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 0.4 | 4.8 | 5.9 | 4.8 | 6.4 | -0.1 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 1.0 | 4.3 | 6.1 | 6.5 | 4.8 | 0.3 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the body image scale, a higher score indicates a better body image. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -1.5 | 0.8 | 1.5 | -0.4 | -0.3 | 1.8 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -4.5 | -1.7 | -1.4 | -1.4 | -2.3 | -5.6 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -1.6 | -3.0 | -2.8 | -2.6 | -1.1 | -5.6 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score indicates more severe disease symptom(s). (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -4.1 | -10.0 | -9.9 | -8.7 | -6.2 | -4.5 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -4.0 | -9.1 | -8.8 | -7.8 | -8.7 | -3.5 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -4.4 | -7.0 | -7.9 | -6.5 | -7.9 | -3.7 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 3.9 | 9.2 | 12.3 | 12.1 | 11.7 | 8.8 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 4.7 | 8.5 | 9.8 | 10.8 | 12.7 | 5.8 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 3.3 | 6.3 | 8.0 | 10.0 | 9.5 | 3.2 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 4.0 | 1.2 | -0.4 | 1.2 | 2.3 | -1.0 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 2.5 | 1.0 | 1.7 | 1.9 | 2.2 | 0.6 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 5.6 | 3.5 | 2.9 | 4.7 | 4.3 | 3.8 |
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score
EQ-5D is a self-administered questionnaire that assesses health-related quality of life. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where higher EQ-5D scores represent better health status. A positive change from baseline score indicates improvement in health status and better health state. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -0.0 | 0.1 | 0.1 | 0.1 | 0.1 | 0.0 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 0.0 | 0.1 | 0.1 | 0.1 | 0.1 | 0.0 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 0.0 | 0.1 | 0.1 | 0.1 | 0.1 | 0.0 |
Number of Participants With Adverse Events (AEs) During the Active Treatment Phase
A TEAE is any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. (NCT00689936)
Timeframe: From first dose of study drug through 28 days following the discontinuation visit from active treatment phase; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | Participants (Number) |
|---|
| ≥ 1 adverse event (AE) | ≥ 1 grade (Gr) 3 or 4 AE | ≥ 1 grade (Gr) 5 AE | ≥ 1 serious adverse event (SAE) | ≥ 1 AE related to Lenalidomide/Dex/Mel/Pred/Thal | ≥ 1 AE related to Lenalidomide | ≥ 1 AE related to dexamethasone | ≥ 1 AE related to melphalan | ≥ 1 AE related to prednisone | ≥ 1 AE related to thalidomide | ≥1 AE related to Lenalidomide/Dex or Mel/Pred/Thal | ≥ 1 Gr 3 or 4 AE related to Len/Dex/Mel/Pred/Thal | ≥ 1 grade 3 or 4 AE related to Lenalidomide | ≥ 1 grade 3 or 4 AE related to dexamethasone | ≥ 1 grade 3 or 4 AE related to melphalan | ≥ 1 grade 3 or 4 AE related to prednisone | ≥ 1 grade 3 or 4 AE related to Thalidomide | ≥1Gr 3 or 4 AE related to Len/Dex or Mel/Pred/Thal | ≥ 1 Grade 5 AE related to Len/Dex/Mel/Pred/Thal | ≥ 1 Grade 5 AE related to Lenalidomide | ≥ 1 Grade 5 AE related to Dexamethasone | ≥ 1 Grade 5 AE related to melphalan | ≥ 1 Grade 5 AE related to prednisone | ≥ 1 Grade 5 AE related to Thalidomide | ≥1 Grade 5 AE related to Len/Dex or Mel/Pred/Thal | ≥1 SAE related to Len/Dex/Mel/Pred/Thal | ≥1 SAE related to Lenalidomide | ≥1 SAE related to dexamethasone | ≥1 SAE related to melphalan | ≥1 SAE related to prednisone | ≥1 SAE related to thalidomide | ≥1 SAE related to Len/Dex or Mel/Pred/Thal | ≥1AE leading to Len/Dex/Mel/Pred/Thal Withdrawal | ≥1 AE leading to Lenalidomide withdrawal | ≥1 AE leading to dexamethasone withdrawal | ≥1 AE leading to melphalan withdrawal | ≥1 AE leading to prednisone withdrawal | ≥1 AE leading to Thalidomide withdrawal | ≥1AE leading to Len/DexOR Mel/Pred/Thal Withdrawal | ≥1AE leading to Len/Dex/Mel/Pred/Thal reduction | ≥1 AE leading to Lenalidomide reduction | ≥1 AE leading to dexamethasone reduction | ≥1 AE leading to melphalan reduction | ≥1 AE leading to prednisone reduction | ≥1 AE leading to thalidomide reduction | ≥1AE leading to Len/Dex or Mel/Pred/Thal reduction | ≥1 AE leading to Rd or MPT interruption | ≥1 AE leading to Lenalidomide interruption | ≥1 AE leading to dexamethasone interruption | ≥1 AE leading to melphalan interruption | ≥1 AE leading to prednisone interruption | ≥1 AE leading to Thalidomide interruption | ≥1 AE leading to Len and Dex or MPT interruption |
|---|
| Lenalidomide and Dexamethasone Rd18 | 536 | 433 | 36 | 308 | 501 | 481 | 410 | 0 | 0 | 0 | 269 | 326 | 290 | 177 | 0 | 0 | 0 | 104 | 11 | 9 | 7 | 0 | 0 | 0 | 5 | 158 | 130 | 97 | 0 | 0 | 0 | 64 | 109 | 93 | 104 | 0 | 0 | 0 | 84 | 214 | 155 | 118 | 0 | 0 | 0 | 20 | 321 | 301 | 280 | 0 | 0 | 0 | 241 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 529 | 453 | 50 | 359 | 506 | 482 | 429 | 0 | 0 | 0 | 269 | 373 | 342 | 229 | 0 | 0 | 0 | 131 | 17 | 12 | 16 | 0 | 0 | 0 | 11 | 195 | 165 | 130 | 0 | 0 | 0 | 95 | 157 | 109 | 152 | 0 | 0 | 0 | 96 | 279 | 203 | 170 | 0 | 0 | 0 | 30 | 368 | 353 | 319 | 0 | 0 | 0 | 290 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 539 | 480 | 38 | 270 | 527 | 0 | 0 | 441 | 326 | 493 | 145 | 423 | 0 | 0 | 307 | 118 | 316 | 49 | 10 | 0 | 0 | 6 | 5 | 5 | 2 | 142 | 0 | 0 | 75 | 62 | 94 | 27 | 153 | 0 | 0 | 83 | 78 | 146 | 71 | 348 | 0 | 0 | 199 | 47 | 254 | 2 | 419 | 0 | 0 | 328 | 324 | 388 | 249 |
Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase
Neutrophil counts was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale. (NCT00689936)
Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | participants (Number) |
|---|
| Normal Baseline Grade to Normal Postbaseline Grade | Normal Baseline Grade to Grade 1 postbaseline | Normal Baseline Grade to Grade 2 postbaseline | Normal Baseline Grade to Grade 3 postbaseline | Normal Baseline Grade to Grade 4 postbaseline | Grade 1 Baseline to Normal postbaseline | Grade1 Baseline to Grade 1 postbaseline | Grade 1 Baseline to Grade 2 postbaseline | Grade 1 Baseline to Grade 3 postbaseline | Grade 1 Baseline to Grade 4 postbaseline | Grade 2 Baseline to normal postbaseline | Grade 2 Baseline to Grade 1 postbaseline | Grade 2 Baseline to Grade 2 postbaseline | Grade 2 Baseline to Grade 3 postbaseline | Grade 2 Baseline to Grade 4 postbaseline | Grade 3 Baseline to Normal postbaseline | Grade 3 Baseline to Grade 1 postbaseline | Grade 3 Baseline to Grade 2 postbaseline | Grade 3 Baseline to Grade 3 postbaseline | Grade3 Baseline to Grade 4 postbaseline | Grade 4 Baseline to Normal postbaseline Grade | Grade 4 Baseline to Grade 1 postbaseline Grade | Grade 4 Baseline to Grade 2 postbaseline | Grade 4 Baseline Grade to Grade 3 postbaseline | Grade 4 Baseline to Grade 4 postbaseline |
|---|
| Lenalidomide and Dexamethasone Rd18 | 133 | 85 | 109 | 71 | 30 | 6 | 11 | 15 | 30 | 4 | 0 | 1 | 11 | 18 | 5 | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 103 | 96 | 121 | 70 | 21 | 7 | 8 | 17 | 25 | 9 | 1 | 1 | 14 | 18 | 9 | 0 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 37 | 79 | 128 | 141 | 45 | 2 | 2 | 11 | 20 | 21 | 0 | 1 | 7 | 21 | 10 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase
Renal function was assessed for participants from baseline to the most extreme value in creatinine clearance calculated using the Cockcroft-Gault estimation. (NCT00689936)
Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | participants (Number) |
|---|
| CrCl< 30 mL/min to CrCl< 30 mL/min | CrCl < 30 mL/min to CrCl ≥ 30 but < 50 mL/min | CrCl < 30 mL/min to CrCl ≥ 50 but < 80 mL/min | CrCl< 30 mL/min to ≥ 80 mL/min | CrCl≥ 30 but < 50 mL/min to < 30 mL/min | CrCl ≥ 30 but < 50 mL/min to CrCl ≥ 30 but < 50 mL | CrCl ≥ 30 but < 50 mL/min to CrCl ≥ 50 but < 80 mL | CrCl ≥ 30 but < 50 mL/min to ≥ 80 mL/min | CrCl ≥ 50 but < 80 mL to CrCl< 30 mL/min | CrCl ≥ 50 but < 80 mL to CrCl ≥ 30 but < 50 mL/min | CrCl ≥ 50 but < 80 mL to CrCl ≥ 50 but < 80 mL/min | CrCl ≥ 50 but < 80 mL to ≥ 80 mL/min | CrCl ≥ 80 mL/min to CrCl< 30 mL/min | CrCl ≥ 80 mL/min to CrCl ≥ 30 but < 50 mL/min | CrCl ≥ 80 mL/min to CrCl ≥ 50 but < 80 mL/min | CrCl ≥ 80 mL/min to CrCl ≥ 80 mL/min |
|---|
| Lenalidomide and Dexamethasone Rd18 | 17 | 14 | 8 | 2 | 2 | 41 | 55 | 12 | 0 | 1 | 130 | 99 | 1 | 0 | 10 | 114 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 15 | 18 | 7 | 2 | 1 | 37 | 67 | 9 | 0 | 4 | 112 | 107 | 0 | 0 | 6 | 109 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 19 | 19 | 5 | 0 | 0 | 41 | 65 | 2 | 0 | 4 | 102 | 97 | 0 | 0 | 9 | 121 |
Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase
Hemoglobin was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale. (NCT00689936)
Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | participants (Number) |
|---|
| Normal Baseline Grade to Normal Postbaseline Grade | Normal Baseline Grade to Grade 1 postbaseline | Normal Baseline Grade to Grade 2 postbaseline | Normal Baseline Grade to Grade 3 postbaseline | Normal Baseline Grade to Grade 4 postbaseline | Grade 1 Baseline to Normal postbaseline | Grade 1 Baseline to Grade 1 postbaseline | Grade1 Baseline to Grade 2 postbaseline | Grade 1 Baseline to Grade 3 postbaseline | Grade 1 Baseline to Grade 4 postbaseline | Grade 2 Baseline to normal postbaseline | Grade 2 Baseline to Grade 1 postbaseline | Grade 2 Baseline to Grade 2 postbaseline | Grade 2 Baseline to Grade 3 postbaseline | Grade 2 Baseline to Grade 4 postbaseline | Grade 3 Baseline to Normal postbaseline | Grade 3 Baseline to Grade 1 postbaseline | Grade 3 Baseline to Grade 2 postbaseline | Grade 3 Baseline to Grade 3 postbaseline | Grade 3 Baseline to Grade 4 postbaseline | Grade 4 Baseline to Normal postbaseline | Grade 4 Baseline to Grade 1 postbaseline | Grade 4 Baseline to Grade 2 postbaseline | Grade 4 Baseline to Grade 3 postbaseline | Grade 4 Baseline to Grade 4 postbaseline |
|---|
| Lenalidomide and Dexamethasone Rd18 | 10 | 30 | 8 | 1 | 0 | 0 | 126 | 123 | 17 | 5 | 0 | 12 | 135 | 41 | 9 | 0 | 1 | 4 | 8 | 3 | 0 | 0 | 0 | 1 | 1 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 6 | 39 | 8 | 0 | 0 | 0 | 106 | 128 | 25 | 2 | 0 | 8 | 125 | 48 | 4 | 0 | 0 | 12 | 10 | 5 | 0 | 0 | 0 | 0 | 1 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 9 | 25 | 4 | 1 | 0 | 0 | 110 | 123 | 20 | 4 | 0 | 14 | 133 | 47 | 11 | 0 | 0 | 10 | 10 | 2 | 0 | 0 | 1 | 0 | 2 |
Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC
Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 35.0 |
| Lenalidomide and Dexamethasone Rd18 | 22.1 |
| Melphalan + Prednisone + Thalidomide (MPT) | 22.3 |
Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS)
Overall survival was defined as the time between randomization and death. Participants, who died, regardless of the cause of death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the participant was known to be alive. (NCT00689936)
Timeframe: From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 59.1 |
| Lenalidomide and Dexamethasone Rd18 | 62.3 |
| Melphalan + Prednisone + Thalidomide (MPT) | 49.1 |
Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis
Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy. Those who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy. (NCT00689936)
Timeframe: From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 36.7 |
| Lenalidomide and Dexamethasone Rd18 | 28.5 |
| Melphalan + Prednisone + Thalidomide (MPT) | 26.7 |
Kaplan Meier Estimates of Time to Treatment Failure (TTF)
TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by IRAC based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death. (NCT00689936)
Timeframe: From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 16.9 |
| Lenalidomide and Dexamethasone Rd18 | 17.2 |
| Melphalan + Prednisone + Thalidomide (MPT) | 14.1 |
Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis
TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by the investigators assessment based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death. (NCT00689936)
Timeframe: From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 16.9 |
| Lenalidomide and Dexamethasone Rd18 | 17.2 |
| Melphalan + Prednisone + Thalidomide (MPT) | 14.1 |
Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis
PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's). (NCT00689936)
Timeframe: From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 26.0 |
| Lenalidomide and Dexamethasone Rd18 | 21.0 |
| Melphalan + Prednisone + Thalidomide (MPT) | 21.9 |
Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase.
Improvement in platelets was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale. (NCT00689936)
Timeframe: Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | participants (Number) |
|---|
| Normal Baseline Grade to Normal Postbaseline Grade | Normal Baseline Grade to Grade 1 postbaseline | Normal Baseline Grade to Grade 2 postbaseline | Normal Baseline Grade to Grade 3 postbaseline | Normal Baseline Grade to Grade 4 postbaseline | Grade1 Baseline to Normal postbaseline Grade | Grade 1 Baseline to Grade 1 postbaseline | Grade 1 Baseline to Grade 2 postbaseline | Grade 1 Baseline to Grade 3 postbaseline | Grade 1 Baseline to Grade 4 postbaseline | Grade 2 Baseline to normal postbaseline Grade | Grade 2 Baseline to Grade 1 postbaseline | Grade 2 Baseline to Grade 2 postbaseline | Grade 2 Baseline to Grade 3 postbaseline | Grade 2 Baseline to Grade 4 postbaseline | Grade 3 Baseline to Normal postbaseline Grade | Grade 3 Baseline to Grade 1 postbaseline | Grade 3 Baseline to Grade 2 postbaseline | Grade 3 Baseline to Grade 3 postbaseline | Grade 3 Baseline to Grade 4 postbaseline |
|---|
| Lenalidomide and Dexamethasone Rd18 | 197 | 211 | 30 | 12 | 5 | 3 | 38 | 19 | 12 | 1 | 0 | 1 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 1 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 197 | 216 | 24 | 15 | 4 | 1 | 34 | 15 | 10 | 2 | 0 | 0 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 2 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 165 | 208 | 27 | 31 | 11 | 6 | 51 | 7 | 10 | 1 | 0 | 2 | 1 | 2 | 2 | 0 | 0 | 1 | 1 | 0 |
Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -4.6 | 6.3 | 8.6 | 9.4 | 9.1 | 3.8 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -2.7 | 2.4 | 6.3 | 7.8 | 8.0 | -0.3 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -2.4 | 4.1 | 8.2 | 11.8 | 14.5 | -1.0 |
Time to First Response Based on the Investigator Assessment at the Time of Final Analysis
The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria assessed by the investigator. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm.
| Intervention | months (Median) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 1.8 |
| Lenalidomide and Dexamethasone Rd18 | 1.8 |
| Melphalan + Prednisone + Thalidomide (MPT) | 2.8 |
Percentage of Participants With an Objective Response Based on IRAC Review
Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined as: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 75.1 |
| Lenalidomide and Dexamethasone Rd18 | 73.4 |
| Melphalan + Prednisone + Thalidomide (MPT) | 62.3 |
Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis
Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas. (NCT00689936)
Timeframe: Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Low-Dose Dexamethasone (Rd) | 80.7 |
| Lenalidomide and Dexamethasone Rd18 | 78.6 |
| Melphalan + Prednisone + Thalidomide (MPT) | 67.5 |
Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Scale is scored between 0 and 100, with a high score indicating a higher level of appetite loss. Negative change from Baseline values indicate improvement in appetite and positive values indicate worsening of appetite. (NCT00689936)
Timeframe: Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | 2.9 | -3.3 | -8.6 | -6.4 | -5.1 | -7.5 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | 1.3 | -5.9 | -9.8 | -7.3 | -8.1 | -1.0 |
,| Melphalan + Prednisone + Thalidomide (MPT) | 1.0 | -6.2 | -13.5 | -10.5 | -12.2 | -2.6 |
Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00689936)
Timeframe: Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit
| Intervention | units on a scale (Mean) |
|---|
| Month 1 | Month 3 | Month 6 | Month 12 | Month 18 | Discontinuation Visit |
|---|
| Lenalidomide and Dexamethasone Rd18 | -1.7 | 1.8 | 0.9 | -1.2 | -2.8 | -2.6 |
,| Lenalidomide and Low-Dose Dexamethasone (Rd) | -1.2 | -0.7 | -0.9 | -1.6 | -2.2 | -4.9 |
,| Melphalan + Prednisone + Thalidomide (MPT) | -1.8 | -1.5 | -0.3 | -0.6 | -0.7 | -7.1 |
Time to Response
Time to response will be measured in the population of subjects with a confirmed response as the time from the date of initiation of treatment to the date of the first documentation of a confirmed response. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). Time to response will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals. (NCT00691704)
Timeframe: 6 months
| Intervention | months (Mean) |
|---|
| High-risk Multiple Myeloma | 2 |
Progression Free Survival
Progression free survival (PFS) is defined for all subjects as the time from the date of initiation of treatment to the date of first documentation of relapse, progression, or death due to any cause. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). PFS survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals. (NCT00691704)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| PFS at 2 years | PFS at 1 year |
|---|
| High-risk Multiple Myeloma | 3 | 9 |
Time to Progression
Time to progression (TTP) is defined for all patients as the time from initiation of treatment to disease progression with deaths owing to causes other than progression not counted as events, but censored (Durie et al., 2006). (NCT00691704)
Timeframe: 6 years
| Intervention | months (Mean) |
|---|
| High-risk Multiple Myeloma | 11 |
Overall Survival
Overall survival is defined as the time from the date of initiation of treatment to the date of death due to any cause. Overall response rate will be estimated with its 80% confidence interval, and the numbers of subjects achieving a sustained complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) will be tabulated. Overall survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals. (NCT00691704)
Timeframe: 6 years
| Intervention | months (Mean) |
|---|
| High-risk Multiple Myeloma | 36 |
Duration of Response
The duration of response, defined only among the responders, is measured from start of achieving Partial Response (PR) [first observation of PR before confirmation] to the time of disease progression, with deaths owing to causes other than progression not counted as events, but censored (Durie et al., 2006). Duration of response will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals. (NCT00691704)
Timeframe: 6 years
| Intervention | months (Mean) |
|---|
| High-risk Multiple Myeloma | 11 |
Number of Participants With Best Overall Disease Response
Will be monitored simultaneously for each of the subgroups separately using the Bayesian approach of Thall, Simon, Estey. Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. Logistic regression will be will be utilized to assess the effect of patient prognostic factors on the response rate. (NCT00695786)
Timeframe: At the end of 3 courses (84 days)
| Intervention | Participants (Count of Participants) |
|---|
| Best Overall Response - CR | Best Overall Response - CRu Response | Best Overall Response - PR | Best Overall Response - SD | Best Overall Response - PD | Best Overall Response - Inevaluable |
|---|
| Follicular Lymphoma | 56 | 13 | 6 | 1 | 0 | 3 |
,| Marginal Zone Lymphoma | 17 | 2 | 4 | 3 | 1 | 4 |
,| Other Histology | 0 | 0 | 1 | 0 | 0 | 1 |
,| Small Lymphocytic Lymphoma | 8 | 5 | 21 | 3 | 6 | 1 |
Response Rate by Recist Criteria
"radiographic response defined as partial response defined by RECIST:At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD~It is noted that while on average the time frame for scans was 4 months, there were two patients who at 32 and 36 months had not progressed." (NCT00717756)
Timeframe: on average about every 2 months until progression, on average about 4 months.
| Intervention | participants (Number) |
|---|
| Lenalidomide | 6 |
Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD)
"Dose Level 1:~15 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4~Dose Level 2:~20 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4~Dose Level 3:~25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4~Dose Level 4:~25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 30 mg/m2 Doxil daily on day 4" (NCT00724568)
Timeframe: 1 month post treatment
| Intervention | mg (Number) |
|---|
| Revlimid | VELCADE | Dexamethasone | Doxil |
|---|
| Combination Drug Therapy | 25 | 1.3 | 20 | 30 |
The Percentage of Patients That Achieved Partial or Complete Response to Treatment.
"Partial Response:~50% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart.~If present, reduction in 24-hour urinary light chain excretion by either, greater than or equal to 90%, or to <200 mg for at least two determinations six weeks apart.~50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least six weeks.~No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).~Complete Response:~Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of six weeks.~<5% plasma cells in the bone marrow on at least two determinations for a minimum of six weeks.~No increase in the size or number of lytic bone lesions." (NCT00724568)
Timeframe: 24 weeks (8, 21-day cycles)
| Intervention | percentage of patients (Number) |
|---|
| Combination Drug Therapy | 96 |
Number of Patients With Severe Infections
Severe infection requiring more than 2 weeks of antibiotic therapy. (NCT00727415)
Timeframe: At 24 months from study entry (end of follow-up)
| Intervention | participants with severe infecitons (Number) |
|---|
| Phase I-II Lenalidomide | 2 |
Overall Complete Response (CR) Rate (Phase II)
Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. (NCT00727415)
Timeframe: After 6 months from study entry (end of treatment).
| Intervention | percentage of patients in CR (Number) |
|---|
| Phase I-II Lenalidomide | 22.5 |
Maximum Tolerated Dose of Lenalidomide (Phase I)
Maximum tolerated dose of lenalidomide given in combination with fludarabine. (NCT00727415)
Timeframe: The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.
| Intervention | number of patients without DLT (Number) |
|---|
| Dose level 1 - 5 mg | Dose level 2 - 10 mg |
|---|
| Phase I-II Lenalidomide | 6 | 1 |
Toxicity as Assessed by NCI CTCAE v3.0
Data from all subjects who receive any study drug will be included in the safety analyses. (NCT00727415)
Timeframe: At 24 months from study entry (end of follow-up)
| Intervention | Participants who died during the study (Number) |
|---|
| Phase I-II Lenalidomide | 14 |
Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).
(NCT00727415)
Timeframe: After 6 months from study entry (end of treatment).
| Intervention | percentage of participants (Number) |
|---|
| CR according to IgHV mutated | CR according to CD19+/CD38+, <30% | CR according to CD19+/CD38+, >30% | CR according to deletion 11q and 17p, absent |
|---|
| Phase I-II Lenalidomide | 28.00 | 33.33 | 16.67 | 31.82 |
Number of Patients Reaching Disease-free Survival (DSF) Overall
Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. (NCT00727415)
Timeframe: After 6 months from study entry (end of treatment)
| Intervention | percentage of participants on DFS (Number) |
|---|
| Phase I-II Lenalidomide | 35.33 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild Adverse Event (AE), Grade 2 = Moderate AE, Grade 3 = Severe and Undesirable AE, Grade 4 = Life-threatening or Disabling AE, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A TEAE is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. (NCT00737529)
Timeframe: From the first dose of lenalidomide through 28 days after the last dose during the follow-up phase; median (minimum, maximum) duration of treatment was 94.0 (1.0, 1950 days)
| Intervention | participants (Number) |
|---|
| Any TEAE | Any TEAE Related to Investigational Product (IP) | Any TEAE Grade 3-5 AE | Any TEAE Grade 3 AE | Any TEAE Grade 4 AE | Any TEAE Grade 5 AE | Any Grade 3-5 AE Related to IP | Any Grade 3 AE Related to IP | Any Grade 4 AE Related to IP | Any Grade 5 AE Related to IP | Any TEAE Serious Adverse Event (SAE) | Any SAE Related to IP | Any TEAE Leading to Stopping of IP | Any Treatment Related AE Leading to Stopping IP | Any AE Leading to Dose Reduction | Any AE Leading to IP Interruption | Any Treatment Related AE Leading to Dose Reduction | Treatment Related AE Leading to IP Interruption |
|---|
| Lenalidomide | 132 | 118 | 106 | 101 | 57 | 18 | 90 | 88 | 41 | 2 | 70 | 30 | 28 | 16 | 55 | 81 | 52 | 66 |
Time to Complete Response (CR+CRu) According to the Independent Review Committee
Time to Complete Response (CR+CRu) was defined as the time from the first dose of study drug to the date of the first occurrence of at least CRu and was calculated only for participants with CR or CRu. (NCT00737529)
Timeframe: From Day 1 of study drug to first documented CR/CRu or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days
| Intervention | months (Median) |
|---|
| Lenalidomide | 3.9 |
Time to Response (TTR)
Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants. (NCT00737529)
Timeframe: From Day 1 of study drug to time of first documented PR or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days
| Intervention | months (Median) |
|---|
| Lenalidomide | 3.5 |
Overall Survival (OS)
Kaplan Meier estimate of overall survival was calculated from the time the first dose of study drug to death from any cause. Participants who had not died were censored at the last date the participant was known to be alive. (NCT00737529)
Timeframe: From Day 1 of study drug to first documented date of progressive disease or death; up to the final data cut-off date of 30 March 2017; median duration of follow-up for surviving participants was 62.94 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 19.50 |
Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee
The percentage of participants whose best response was CR or CRu. Participants who had discontinued before CR/CRu was observed, or changed to other anti-lymphoma treatments before a CR/CRu response had been observed, were considered as non-responders. CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow. (NCT00737529)
Timeframe: From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 9.0 |
Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee
Kaplan Meier estimates for the duration of CR/CRu was calculated from the date of the first occurrence of CR/CRu to the date of documented disease progression or death (without documented progression) for participants who obtained a CR/CRu; participants who had not progressed (or died) were censored at the last valid assessment. (NCT00737529)
Timeframe: From Day 1 of study drug to progression or early discontinuation; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 24.43 |
Kaplan Meier Estimate of Duration of Response (DoR) According to the Independent Review Committee
Kaplan Meier estimate for the duration of response (DoR) was calculated from the date of the first occurrence of initial response for responders (demonstrating evidence of at least a PR) to the date of first documented disease progression (any new lesion or increase by ≥ 50% of previously involved sites from nadir) or death (without documented progression) for participants who responded; participants who had not progressed (or died) were censored at the last valid assessment. (NCT00737529)
Timeframe: From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days.
| Intervention | months (Median) |
|---|
| Lenalidomide | 16.64 |
Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee
Kaplan Meier estimate of time to progression was calculated as time from the start of the study drug therapy to the first observation of disease progression. Participants who died without progression were censored at the date of death; otherwise, the censoring rules presented above for PFS applied to the analysis of TTP. Progressive Disease(PD): Appearance of new lesion or increase by ≥50% from previously involved sites from nadir (NCT00737529)
Timeframe: From Day 1 of study drug to first documented time of progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 5.46 |
Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee
Kaplan Meier estimates of PFS was defined as the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever comes first. If a participant had not progressed or died, PFS was censored at the time of last adequate assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last adequate tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. (NCT00737529)
Timeframe: From Day 1 of study drug to first documented date of disease progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 4.01 |
Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee
Time to treatment failure (TTF) was calculated from the start of study drug therapy to early discontinuation from treatment due to any cause, including disease progression, toxicity, or death and was based on site-reported data. (NCT00737529)
Timeframe: From Day 1 of study drug to first documented time of treatment failure; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days
| Intervention | months (Median) |
|---|
| Lenalidomide | 3.75 |
Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)
Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed, or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. (NCT00737529)
Timeframe: From Day 1 of study treatment to progession or early treatment discontinuation; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 29.9 |
Progression-free Survival (PFS)
PFS is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression or death. The distribution of PFS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the PFS distribution are provided. (NCT00742560)
Timeframe: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
| Intervention | months (Median) |
|---|
| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 6.08 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 22.23 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | NA |
| Total (Phase 1) | 32.92 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 32.49 |
| Elotuzumab 10 mg/kg Administered as an IV Infusion in Combinat | 25.00 |
| Total (Phase 2) | 28.62 |
Time to Progression (TTP)
TTP is defined as the time from first dose (phase 1) or time from randomization (phase 2) to disease progression. The distribution of TTP was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the TTP distribution are provided. (NCT00742560)
Timeframe: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
| Intervention | months (Median) |
|---|
| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 6.08 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 11.53 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 52.93 |
| Total (Phase 1) | 52.93 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 32.49 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 19.94 |
| Total (Phase 2) | 28.16 |
Mean Serum Concentrations of Elotuzumab During Cycle 1
Blood samples were collected during Phase 1, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours) and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). Blood samples were collected during Phase 2, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) and 2 hours post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). The samples were analyzed for the concentration of elotuzumab using validated analytical methods. Mean serum concentrations on Cycle 1, Days 1, 8, 15, and 22 (measured in μg/mL) are reported overall (across Phase 1 and Phase 2) by dose. (NCT00742560)
Timeframe: Cycle 1: Days 1 (pre-infusion and 0.5, 2 and 4 hours post-infusion), 8 (pre-infusion and 0.5 and 2 hours post-infusion), 15 (pre-infusion and 0.5 hours and 2 hours post-infusion), and 22 (pre-infusion and 0.5, 2, and 4 hours post-infusion)
| Intervention | μg/mL (Mean) |
|---|
| Day 1: 0 hours | Day 1: 0.5 hours | Day 1: 4 hours | Day 8: 0 hours | Day 8: 0.5 hours | Day 15: 0 hours | Day 15: 0.5 hours | Day 22: 0 hours | Day 22: 0.5 hours | Day 22: 2 hours | Day 22: 4 hours |
|---|
| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone | 0.00 | 78.48 | 85.56 | 32.44 | 133.37 | 49.84 | 140.09 | 61.93 | 168.61 | 268.53 | 128.94 |
Mean Serum Concentrations of Elotuzumab During Cycle 1
Blood samples were collected during Phase 1, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours) and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). Blood samples were collected during Phase 2, Cycle 1, prior to elotuzumab infusion (time 0 hours) and 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 1), 30 minutes (0.5 hours) and 2 hours post-infusion (Day 8 and Day 15), or 30 minutes (0.5 hours), 2 hours, and 4 hours post-infusion (Day 15). The samples were analyzed for the concentration of elotuzumab using validated analytical methods. Mean serum concentrations on Cycle 1, Days 1, 8, 15, and 22 (measured in μg/mL) are reported overall (across Phase 1 and Phase 2) by dose. (NCT00742560)
Timeframe: Cycle 1: Days 1 (pre-infusion and 0.5, 2 and 4 hours post-infusion), 8 (pre-infusion and 0.5 and 2 hours post-infusion), 15 (pre-infusion and 0.5 hours and 2 hours post-infusion), and 22 (pre-infusion and 0.5, 2, and 4 hours post-infusion)
| Intervention | μg/mL (Mean) |
|---|
| Day 1: 0 hours | Day 1: 0.5 hours | Day 1: 2 hours | Day 1: 4 hours | Day 8: 0 hours | Day 8: 0.5 hours | Day 8: 2 hours | Day 15: 0 hours | Day 15: 0.5 hours | Day 22: 0 hours | Day 22: 0.5 hours | Day 22: 2 hours | Day 22: 4 hours |
|---|
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone | 0.00 | 217.90 | 213.31 | 251.34 | 92.47 | 281.53 | 268.35 | 111.11 | 282.29 | 135.92 | 310.03 | 298.85 | 538.88 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone | 0.00 | 434.20 | 388.58 | 525.98 | 168.55 | 593.80 | 520.97 | 298.82 | 661.91 | 308.02 | 699.70 | 704.48 | 981.16 |
Number of Participants With Infusion Reactions
During Phase 1, a list of 118 pre-defined MedDRA preferred terms that had been adjudicated to be clinically relevant to infusion reactions by a safety committee was used to search for TEAEs that could potentially be associated with an infusion reaction following elotuzumab administration. Examples of these terms included angioedema, bronchospasm, chills, flushing, pyrexia, rash and urticaria. During Phase 2, the method for capturing TEAEs associated with an infusion reaction was modified to include investigators' designation of AEs judged as clinically relevant infusion reactions. The number of participants infusion reactions are provided overall and by highest toxicity grade (CTCAE v 3.0). (NCT00742560)
Timeframe: Cycles 1 and 2: Days 1, 8, 15, and 22 (day of infusion of elotuzumab) and Days 2, 9, 16, and 23 (day following infusion); and Cycles 3 and greater: Days 1 and 15 (day of infusion) and Days 2 and 16 (day after infusion) (up to 95 months)
| Intervention | participants (Number) |
|---|
| Any reaction | Grade 5 | Grade 4 | Grade 3 | Grade 2 | Grade 1 |
|---|
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 3 | 0 | 0 | 0 | 1 | 2 |
,| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 5 | 0 | 0 | 1 | 1 | 3 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 20 | 0 | 1 | 2 | 5 | 12 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 3 | 0 | 0 | 0 | 1 | 2 |
,| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 2 | 0 | 0 | 0 | 0 | 2 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either definitely related, probably related, possibly related or unrelated. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section. (NCT00742560)
Timeframe: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 60 days after the last dose of study drug (up to 95 months)
| Intervention | participants (Number) |
|---|
| Any TEAE | Any TESAE | TEAEs ≥ Grade 3 | TEAEs related to study drug | TESAEs related to study drug |
|---|
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 3 | 3 | 3 | 3 | 0 |
,| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 36 | 21 | 32 | 29 | 2 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 22 | 12 | 19 | 16 | 2 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 37 | 21 | 25 | 26 | 5 |
,| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 3 | 0 | 2 | 3 | 0 |
Plasma Cell Myeloma Cytogenetic Subtype
Plasma cell myeloma cytogenetic subtype was assessed at the screening visit using standard karyotyping and/or fluorescence in situ hybridization. The number of participants in each cytogenetic risk category are provided: High Risk (International Staging System [ISS] stage II or III and t(4;14) or del(17p) abnormality); Standard Risk (not high or low risk); and Low Risk (ISS stage I or II and absence of t(4;14), del(17p) and 1q21 abnormalities AND age < 55). (NCT00742560)
Timeframe: Screening (up to 14 days prior to dosing)
| Intervention | participants (Number) |
|---|
| High Risk | Standard Risk | Low Risk | Not Reported |
|---|
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 0 | 3 | 0 | 0 |
,| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 1 | 30 | 2 | 3 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 0 | 17 | 3 | 2 |
,| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 3 | 24 | 3 | 7 |
,| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 1 | 2 | 0 | 0 |
Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1)
MTD was determined by testing increasing doses up to 20 mg/kg once daily dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (dose limiting toxicity [DLT]) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria for Adverse Events (CTCAE) Grade 4 neutropenia in specific conditions, platelets < 10,000 cells/mm^3 that do not recover to 25,000 cells/mm^3; and specific non-hematologic/biochemical toxicities CTCAE Grade 3 or 4 (except fatigue and Grade 3 infections); CTCAE version 3.0 were used. (NCT00742560)
Timeframe: 4 weeks
| Intervention | mg/kg (Number) |
|---|
| Phase 1 Elotuzumab + Lenalidomide and Dexamethasone | 20 |
Duration of Response
Duration of response is defined as the time from the initial objective response to disease progression or death, whichever occurs first. The distribution of duration of response was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the median for the duration of response distribution are provided. (NCT00742560)
Timeframe: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
| Intervention | months (Median) |
|---|
| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 4.47 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | 9.92 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1) | NA |
| Total (Phase 1) | NA |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 34.83 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2) | 29.01 |
| Total (Phase 2) | 29.24 |
Percentage of Participants With Treatment-emergent Anti-elotuzumab Antibody (ADA)
Treatment-emergent (post-dose) positive elotuzumab-specific ADA is differentiated from pre-existing (positive at the predose time point) positive elotuzumab-specific ADA. The percentage of participants with confirmed treatment-emergent ADA overall by dose is provided. (NCT00742560)
Timeframe: From screening through 60-day follow up period (up to 101 months)
| Intervention | percentage of participants (Number) |
|---|
| Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone | 0 |
| Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone | 6 |
| Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone | 5 |
Percentage of Participants With Progression-free Survival (PFS) and Overall Survival (OS).
Assess the time to disease progression and overall survival. (Progressive disease is defined as at least one of the following: more than or equal to 50% increase in the sum of the products of the greatest diameters of at least 2 lymph nodes on 2 consecutive determinations 2 weeks apart (at least one node must be ≥ 2 cm) or new palpable lymph nodes, more than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the costal margin or appearance of palpable hepatomegaly or splenomegaly not previously present, more than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5.0 x109/L, OR transformation to a more aggressive histology (e.g. Richter's syndrome or prolymphocytic leukemia with >55% prolymphocytes)). (NCT00751296)
Timeframe: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis.
| Intervention | percentage of participants (Number) |
|---|
| Overall survival | Progression free survival |
|---|
| Lenalidiomide | 85.3 | 64.6 |
To Assess the Efficacy (Response Rate) of Oral Lenalidomide in the Treatment of Patients With Symptomatic, Previously Untreated, Chronic Lymphocytic Leukemia (CLL)
"The primary endpoint was objective response to lenalidomide (Complete response +Partial response) evaluated as per the revised 1996 National Cancer Institute Working Group Guidelines.~Complete response: absence of lymphadenopathy and organomegaly by physical exam and radiology, absence of constitutional symptoms, normal CBC. Bone marrow to be done 2 months after the above criteria are met, must be normocellular, with <30% lymphocytes.~Partial Response: ≥ 50% decrease in the peripheral blood lymphocytes from pre-treatment value, ≥ 50% reduction in lymphadenopathy and organomegaly by physical exam or on CT scan. one or more of the following: neutrophils ≥ 1.5 x109/L, platelets > 100 x109/L or 50% improvement over baseline, hemoglobin > 110 g/L or 50% improvement over baseline (without transfusion)." (NCT00751296)
Timeframe: Patients will be treated with lenalidomide until disease progression or 2 cycles past CR (no maximum of cycles). Participants were followed upto 53.2 months for the final data analysis.
| Intervention | participants (Number) |
|---|
| Complete response | Partial response | Stable Disease |
|---|
| Lenalidiomide | 5 | 13 | 6 |
Number of Patients With Each Worst-Grade Toxicity
Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death. Toxicities present at baseline and continuing without change in grade are excluded when considering worst-grade toxicity. (NCT00765245)
Timeframe: 30 days after completing treatment, for up to 13 months
| Intervention | participants (Number) |
|---|
| Number of patients with WGT=1 | Number of patients with WGT=2 | Number of patients with WGT=3 | Number of patients with WGT=4 | Number of patients with WGT=5 |
|---|
| Arm I: Lenalidomide | 2 | 6 | 6 | 5 | 0 |
,| Arm II: Lenalidomide and Rituximab IV | 0 | 8 | 8 | 5 | 0 |
Disease-free Survival at 2 Years
Disease-free survival is the estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method where death is an event, with censoring for non-expired patients at last known date alive. (NCT00765245)
Timeframe: From on-treatment date to disease recurrence, up to 2 years
| Intervention | years (Median) |
|---|
| Arm I: Lenalidomide | 0.818 |
| Arm II: Lenalidomide and Rituximab IV | 0.757 |
Disease-free Survival at 1 Year
Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Those who are alive and without relapse are censored at the last date known alive. (NCT00765245)
Timeframe: From on-treatment date to disease recurrence, up to 1 year
| Intervention | years (Mean) |
|---|
| Arm I: Lenalidomide | 0.818 |
| Arm II: Lenalidomide and Rituximab IV | 0.90 |
Progression-free Survival (PFS) Rate at 12 Months
"PFS rate at 12 months is defined as the percentage of participants who are alive and progression-free at 12 months. Progression is exclusively defined as a patient with progressive disease while receiving treatment with lenalidomide in combination with dexamethasone. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in:~Serum M-component (absolute increase >= 0.5g/dl)~Urine M-component (absolute increase >= 200mg/24hour~Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl~Bone marrow plasma cell percentage (absolute increase of >=10%)" (NCT00772915)
Timeframe: 12 months from registration
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide With On-Demand Dexamethasone | 79 |
Progression-free Survival (PFS)
"PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.~Progression was defined as any one or more of the following:An increase of 25% from lowest confirmed response in:~Serum M-component (absolute increase >= 0.5g/dl)~Urine M-component (absolute increase >= 200mg/24hour~Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl~Bone marrow plasma cell percentage (absolute increase of >=10%)" (NCT00772915)
Timeframe: Time from registration to progression or death (up to 3 years)
| Intervention | months (Median) |
|---|
| Lenalidomide With On-Demand Dexamethasone | 27 |
Overall Survival (OS)
OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 3 years from randomization. The median OS with 95% CI was estimated using the Kaplan Meier method (NCT00772915)
Timeframe: Time from registration to death (up to 3 years)
| Intervention | months (Median) |
|---|
| Lenalidomide With On-Demand Dexamethasone | 61.1 |
Confirmed Response Rate
"Confirmed response rate is defined as the percentage of participants who achieved a response that was confirmed on 2 consecutive evaluations during treatment~Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM)~Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM~Partial Response PR): >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels" (NCT00772915)
Timeframe: Up to 18 cycles from registration
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide With On-Demand Dexamethasone | 61 |
Overall Survival (OS)
Overall Survival (OS) is defined as the time from randomization to death from any cause. OS will be censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT00774345)
Timeframe: Up to approximately 11 years
| Intervention | Months (Median) |
|---|
| Lenalidomide | 95.09 |
| Placebo | 73.28 |
Progression Free Survival 2 (PFS2)
Progression Free Survival (PFS2) assessed by investigator is defined as the time from randomization to the second objective disease progression, or death from any cause, whichever occurs first. (NCT00774345)
Timeframe: Up to 6 years
| Intervention | Months (Median) |
|---|
| Lenalidomide | NA |
| Placebo | 35.9 |
Number of Participants With Adverse Events (AEs)
Number of participants with adverse events (AEs) that measure type, frequency and severity of AEs graded by National Cancer Institute Common Terminology Criteria (NCI CTCAE V 3.0) including any grade adverse events (AEs), Grade 3-4 AEs, AEs related to study drug, grade 3-4 AEs related to study drug. (NCT00774345)
Timeframe: From first dose to 30 days post last dose (up to 9 years)
| Intervention | Participants (Number) |
|---|
| Adverse Events (AEs) | Grade 3-4 AEs | AEs related to Study drugs | Grade 3-4 AEs related to Study drugs |
|---|
| Lenalidomide | 155 | 136 | 143 | 117 |
,| Placebo | 149 | 73 | 98 | 41 |
Time Until Progression After Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphomas With Rituximab Resistance
Progression free survival time in months (NCT00783367)
Timeframe: 9 years from enrollment of first subject
| Intervention | months (Median) |
|---|
| Cohort 1 | 22.2 |
| Cohort 2 | 22.4 |
Response Rate to Lenalidomide-dexamethasone + Rituximab Therapy in Relapsed Small B-cell Lymphoma With Rituximab Resistance
Response rate is defined as a complete response or partial response using anatomic criteria of the International Workshop Response Critieria (Cheson, 1999). (NCT00783367)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 | 14 |
| Cohort 2 | 13 |
Assessment of Tumor Response
"The proportion of responses was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients.~Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.~Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed." (NCT00784927)
Timeframe: Up to 1 year from registration.
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) |
|---|
| Treatment | 30.3 | 54.5 |
Progression-free Survival Time
"Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death.~Progressive disease is defined as having one of the following:~The appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size.~At least a 50% increase from nadir in the sum of the product of the dimension (SPD) of any previously involved nodes.~At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis." (NCT00784927)
Timeframe: Up to 1 year from registration.
| Intervention | months (Median) |
|---|
| Treatment | 38.3 |
Survival Time
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT00784927)
Timeframe: Up to 1 year from registration.
| Intervention | months (Median) |
|---|
| Treatment | NA |
Time to Treatment Failure
Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier. (NCT00784927)
Timeframe: Up to 1 year from registration.
| Intervention | months (Median) |
|---|
| Treatment | NA |
Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia).
"The proportion of responses in Waldenstrom's macroglobulinemia was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients.~Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.~Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed." (NCT00784927)
Timeframe: Up to 1 year from registration.
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) |
|---|
| Treatment | 6.7 | 66.7 |
Progression-free Survival
Progression-free survival is the time from registration to disease progression or death. Patients alive without disease progression were censored at the time of the last disease assessment. (NCT00790842)
Timeframe: 56 months
| Intervention | Months (Median) |
|---|
| Group A=30-60 CrCl (mL/Min) | 12.6 |
| Group B=CrCL<30 mL/Min Not on Dialysis | 11.4 |
| Group C=CrCL<30 mL/Min and on Dialysis | NA |
Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR]
Per International Myeloma Working Group criteria, complete response (CR): negative immunofixation of serum and urine, normalization of free light chain (FLC) ratio if at study entry FLC was only measurable non-bone parameter, <5% plasma cells in bone marrow, disappearance of any soft tissue plasma cytomas; stringent complete response (sCR): all of above, + normal serum FLC ratio in all patients and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; partial response (PR): >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to < 200 mg per 24 hours, >=50% decrease in difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio, >=50% reduction in bone marrow plasma cells, if baseline percentage was >=30%, >=50% reduction in size of soft tissue plasmacytoma; very good partial response (VGPR): PR + improvements in serum and urine M-components (NCT00790842)
Timeframe: 56 months
| Intervention | percentage of participants (Number) |
|---|
| Group A CrCl 30-60 mL/Min | 60.0 |
| Group B CrCL<30 mL/Min, Not on Dialysis | 60.0 |
| Group C CrCL<30 mL/Min and on Dialysis | 20.0 |
Overall Survival Time
Overall survival is the time from registration to death from any cause. Patients alive at the time of analysis were censored at the date last known alive. (NCT00790842)
Timeframe: 56 months
| Intervention | months (Median) |
|---|
| Group A=30-60 CrCl (mL/Min) | 20.8 |
| Group B=CrCL<30 mL/Min Not on Dialysis | 20.0 |
| Group C=CrCL<30 mL/Min and on Dialysis | NA |
Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy
"Dose Limiting Toxicity (DLT) was defined as any of the following events determined by the investigator to be possibly, probably, or definitely related to lenalidomide within the first cycle of therapy irrespective of whether the adverse events resolved:~Grade 3 or higher neutropenia with fever ≥38.5 degrees C~Grade 4 neutropenia ≥7 days~Grade 4 or higher thrombocytopenia~Other non-hematologic Grade 4 or higher adverse event not present prior to starting therapy or not due to underlying cause" (NCT00790842)
Timeframe: First cycle of therapy (28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Group A Lenalidomide 10 mg/Day | 0 |
| Group A Lenalidomide 15 mg/Day | 0 |
| Group A Lenalidomide 25 mg/Day | 0 |
| Group B Lenalidomide 15 mg/2 Days | 0 |
| Group B Lenalidomide 25 mg/2 Days | 0 |
| Group B Lenalidomide 15 mg/Day | 0 |
| Group B Lenalidomide 25 mg/Day | 0 |
| Group C Lenalidomide 15 mg 3x/Week | 0 |
| Group C Lenalidomide 10 mg/Day | 0 |
| Group C Lenalidomide 15 mg/Day | 0 |
| Group C Lenalidomide 25 mg/Day | 0 |
Duration of Response
Duration of response was defined as time between the onset of response and disease progression in months, among patients treated at the recommended phase II dose who experienced a response to treatment. Per criteria of the International Myeloma Working Group, progressive disease was defined as one of the following: increase of 25% from best confirmed response in serum M-component, urine M-component, free light chain (FLC), bone marrow plasma cell percentage, or development of new or increase in size of bone lesions or soft tissue plasma cytomas. Development of hypercalcemia that can be attributed solely to the myeloma also constituted progression. (NCT00790842)
Timeframe: 56 months
| Intervention | Months (Median) |
|---|
| Group A=30-60 CrCl (mL/Min) | 21.8 |
| Group B=CrCL<30 mL/Min Not on Dialysis | 8.4 |
| Group C=CrCL<30 mL/Min and on Dialysis | 25.4 |
The Functional Assessment of Chronic Illness Therapy-Fatigue Subscale Score
The FACIT-F subscale is a validated measure of fatigue. In the FACIT-F, the patient rates the intensity of their fatigue and its related symptoms on a scale of 0 to 4. The total score can range between 0 and 52, with higher scores denoting less fatigue. The score 0= worst fatigue possible, 52 indicates no fatigue. The scores reported is the median (IQR) change at 8 weeks compared to baseline. (NCT00792077)
Timeframe: before and after 1st cycle of Lenalidomide treatment, up to 8 weeks
| Intervention | score on a scale (Median) |
|---|
| Lenalidomide | 4 |
Total Sleep Time as Measured by Polysomnography (PSG)
Polysomnography (PSG) was done to measure the total sleep time in minutes. It was measured as a change in total sleep time between the before and after 1st cycle of treatment with Lenalidomide. (NCT00792077)
Timeframe: before and after 1st cycle of Lenalidomide treatment, up to 8 weeks
| Intervention | Minutes (Median) |
|---|
| Lenalidomide | -25.5 |
Epwort Sleep Scale
The Epworth sleep scale is an 8-item questionnaire designed to asses general level of daytime sleepiness, and scores on this instrument range form 0-24, with higher scores indicating greater sleepiness. It was measured as a change in total score between the before and after 1st cycle of treatment with Lenalidomide. (NCT00792077)
Timeframe: before and after 1st cycle of Lenalidomide treatment, up to 8 weeks
| Intervention | score on a scale (Median) |
|---|
| Lenalidomide | -1 |
Progression Free Survival (PFS) Rate at 2 Years After Enrollment in Untreated Patients With Multiple Myeloma.
(NCT00807599)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Continue Lenalidomide and Dexamethasone | 84.6 |
| Stem Cell Transplant x 1 or x 2 | 83.3 |
Overall Survival
(NCT00807599)
Timeframe: up to 4 years
| Intervention | percentage of participants alive (Number) |
|---|
| Continue Lenalidomide and Dexamethasone | 95.7 |
| Stem Cell Transplant x 1 or x 2 | 90.6 |
Number of Participants With Adverse Events (AE)
"An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE):~Death;~Life-threatening event;~Any inpatient hospitalization or prolongation of existing hospitalization;~Persistent or significant disability or incapacity;~Congenital anomaly or birth defect;~Any other important medical event.~The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event.~The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death." (NCT00812968)
Timeframe: After the first study dose until 28 days after completion of/discontinuation from the study (maximum time on study was 155 weeks).
| Intervention | participants (Number) |
|---|
| Any adverse event (AE) | AE related to study drug | Grade 3 or 4 AE | Grade 3 or 4 AE related to study drug | Serious AE (SAE) | SAE related to study drug | AE leading to discontinuation of study drug | Related AE leading to discontinuation | AE leading to a dose reduction or interruption | Related AE leading to dose reduction/interruption | Deaths |
|---|
| Lenalidomide | 11 | 11 | 11 | 11 | 3 | 1 | 0 | 0 | 10 | 9 | 0 |
Percentage of Bone Marrow Myeloblasts
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. (NCT00812968)
Timeframe: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
| Intervention | Percentage of myeloblasts (Median) |
|---|
| Baseline (N=11) | End of Cycle 3 (N=10) | End of Cycle 6 (N=10) |
|---|
| Lenalidomide | 3.77 | 1.47 | 1.79 |
Change From Baseline in Percentage of Bone Marrow Erythroblasts
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. (NCT00812968)
Timeframe: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
| Intervention | Percentage of Bone Marrow Erythroblasts (Median) |
|---|
| Change from Baseline at the end of Cycle 3 | Change from Baseline at the end of Cycle 6 |
|---|
| Lenalidomide | 36.5 | 21.5 |
Percentage of Bone Marrow Promyelocytes
Bone marrow morphology was assessed by the central hematologic reviewers based on the locally-prepared bone marrow smear slide and clot section. (NCT00812968)
Timeframe: Baseline, at the end of Cycle 3 (Day 85) and Cycle 6 (Day 169).
| Intervention | Percentage of promyelocytes (Median) |
|---|
| Baseline (N=11) | End of Cycle 3 (N=10) | End of Cycle 6 (N=10) |
|---|
| Lenalidomide | 5 | 5 | 5 |
Time to Erythroid Response
Time to erythroid response was calculated as the time from the first dose of study drug to the start of the first major or minor erythroid response. Similarly, time to major erythroid response was calculated as the time from the first dose of study drug to the start of the first major erythroid response. (NCT00812968)
Timeframe: From the first dose of study drug through Week 156
| Intervention | weeks (Median) |
|---|
| Time to erythroid response (major or minor) | Time to major erythroid response |
|---|
| Lenalidomide | 2.1 | 6.3 |
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Lenalidomide
Area under the plasma concentration-time curve from time zero to infinity (AUC∞) of lenalidomide after a single dose on Day 1. (NCT00812968)
Timeframe: Day 1 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Lenalidomide | 878.0 |
Change From Baseline in Hemoglobin Concentration
Change in hemoglobin concentration from Baseline to the maximum observed value during the major erythroid response period for major erythroid responders. (NCT00812968)
Timeframe: Baseline and from Day1 until the maximum observed value (up to 155 weeks)
| Intervention | g/dL (Median) |
|---|
| Baseline concentration | Maximum concentration during study | Change from Baseline to maximum value |
|---|
| Lenalidomide | 7.0 | 13.1 | 6.0 |
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Lenalidomide
Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUCt) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 718.4 |
| Lenalidomide: Day 4 | 803.5 |
Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCτ) of Lenalidomide
Area under the plasma concentration-time curve over the dosing interval (AUCτ) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 and 24 hours post-dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 866.5 |
| Lenalidomide: Day 4 | 877.9 |
Terminal Half-life (T1/2) of Lenalidomide
The apparent terminal half-life is the time required for plasma concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached, and calculated as the natural logarithm of 2 (0.693) / Apparent terminal rate constant (λz). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | hours (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 3.26 |
| Lenalidomide: Day 4 | 3.57 |
Time to Maximum Plasma Concentration (Tmax) of Lenalidomide
Time to maximum observed plasma concentration of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | hours (Median) |
|---|
| Lenalidomide: Day 1 | 2.52 |
| Lenalidomide: Day 4 | 2.93 |
Maximum Observed Plasma Concentration (Cmax) of Lenalidomide
Maximum observed plasma concentration of lenalidomide after a single dose on Day and after multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 136 |
| Lenalidomide: Day 4 | 149 |
Number of Participants With a Erythroid Response
"Erythroid response was determined using the International Working Group (IWG) 2000 criteria, categorized as a major response or minor response.~A major response in patients with transfusion-dependent anemia (receiving ≥ 4.5 units of red blood cell (RBC) transfusion during 56 consecutive days at Baseline) is defined as RBC transfusion independence accompanied by a ≥1.0 g/dL increase from Baseline in hemoglobin sustained for 56 days consecutively during the treatment period. In patients with transfusion-independent anemia with hemoglobin < 10 g/dL at Baseline a major response is defined as a > 2.0 g/dL increase from Baseline in hemoglobin sustained for consecutive 56 days.~Minor response in patients with transfusion-dependent anemia defined as ≥ 50% decrease from Baseline in transfusion requirements sustained for consecutive 56 days, and in transfusion-independent patients as 1.0 to 2.0 g/dL increase from Baseline in hemoglobin sustained for consecutive 56 days." (NCT00812968)
Timeframe: Response was assessed every 28 days through Week 156.
| Intervention | participants (Number) |
|---|
| Erythroid responders (major or minor) | Major erythroid responders |
|---|
| Lenalidomide | 11 | 11 |
Duration of Erythroid Response
Duration of erythroid response was calculated as the time from the start of the first major or minor erythroid response to the end of the response. Similarly, duration of major erythroid response was calculated as the time from the start of the first major erythroid response to the end of the response. Response duration was censored at the last adequate assessment for patients who maintained response. (NCT00812968)
Timeframe: From the first dose of study drug through Week 156
| Intervention | weeks (Median) |
|---|
| Duration of erythroid response (major or minor) | Duration of major erythroid response |
|---|
| Lenalidomide | 76.6 | 72.1 |
Number of Participants With a Cytogenetic Response
"Cytogenetic (chromosome structure) abnormalities were assessed by a central cytogenetic reviewer based on prints and cytogenetic reports of the bone marrow sample from the central laboratory. Cytogenetic response was determined using the IWG (2000) criteria and categorized as either a major response or minor response. Twenty metaphases were analyzed for the determination of cytogenetic response.~A major response was defined as no detectable cytogenetic abnormality, if an abnormality was present at Baseline, sustained for consecutive 56 days during the treatment period. A minor response was defined as ≥ 50% reduction from Baseline in abnormal metaphases sustained for consecutive 56 days during the treatment period." (NCT00812968)
Timeframe: Response was assessed every 12 weeks through Week 156
| Intervention | participants (Number) |
|---|
| Major response | Minor response |
|---|
| Lenalidomide | 1 | 5 |
Apparent Terminal Elimination Rate Constant of Lenalidomide
Apparent terminal elimination rate constant of lenalidomide determined after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | 1/h (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 0.213 |
| Lenalidomide: Day 4 | 0.194 |
Number of Participants With a Neutrophil Response
"Neutrophil response was determined using the IWG (2000) criteria. A major response for participants with a Baseline neutrophil count < 1,500/mm^3 is defined as a ≥ 100% increase or a ≥ 500/mm^3 increase, whichever is greater, sustained for consecutive 56 days during the treatment period.~A minor response for participants with a Baseline neutrophil count < 1,500/mm^3 is defined as a ≥ 100% increase, but an absolute increase < 500/mm^3, sustained for consecutive 56 days during the treatment period." (NCT00812968)
Timeframe: Response was assessed every 28 days through Week 156
| Intervention | participants (Number) |
|---|
| Major response | Minor response |
|---|
| Lenalidomide | 1 | 0 |
Apparent Total Plasma Clearance (CL/F) of Lenalidomide
Apparent total plasma clearance (CL/F) of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | mL/minute (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 189.8 |
| Lenalidomide: Day 4 | 189.9 |
Apparent Volume of Distribution (VzF) of Lenalidomide
Apparent volume of distribution of lenalidomide after a single dose on Day 1 and multiple doses (Day 4). (NCT00812968)
Timeframe: Days 1 and 4 at predose and 0.5, 1, 1.5, 2, 3, 4, 6, 9, and 12 hours post-dose.
| Intervention | liters (Geometric Mean) |
|---|
| Lenalidomide: Day 1 | 53.6 |
| Lenalidomide: Day 4 | 58.6 |
Rate of Lenalidomide Related Toxicity During Maintenance Therapy
Rate of toxicities of lenalidomide as maintenance therapy according to the National Cancer Institute Common Toxicity Criteria (CTC) V3. Adverse Events: Possibly Related; Probably Related, or Definitely Related to study treatment. Events are categorized as Grade 1 or 2, or as Grade 3 or 4. (NCT00831766)
Timeframe: 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Leukocytes (total WBC) - low - Grade 1 or 2 | Leukocytes (total WBC) - low - Grade 3 or 4 | ANC/AGC - Grade 1 or 2 | ANC/AGC - Grade 3 or 4 | Platelets - low - Grade 1 or 2 | Platelets - low - Grade 3 or 4 | Fatigue - Grade 1 or 2 | Fatigue - Grade 3 or 4 | Dry skin - Grade 1 or 2 | Dry skin - Grade 3 or 4 | Pruritus/itching - Grade 1 or 2 | Pruritus/itching - Grade 3 or 4 | Rash/desquamation - Grade 1 or 2 | Rash/desquamation - Grade 3 or 4 | Constipation - Grade 1 or 2 | Constipation - Grade 3 or 4 | Diarrhea - Grade 1 or 2 | Diarrhea - Grade 3 or 4 | Nausea - Grade 1 or 2 | Nausea - Grade 3 or 4 | Ulcer, GI - Anus - Grade 1 or 2 | Ulcer, GI - Anus - Grade 3 or 4 | Hemorrhage, GI - Rectum - Grade 1 or 2 | Hemorrhage, GI - Rectum - Grade 3 or 4 | Infection - Skin (cellulitis) Grade 1 or 2 | Infection - Skin (cellulitis) Grade 3 or 4 | AST, SGOT - Grade 1 of 2 | AST, SGOT - Grade 3 or 4 | Pain - Head/headache - Grade 1 or 2 | Pain - Head/headache - Grade 3 or 4 |
|---|
| Maintenance Phase Participants | 1 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 |
Phase I: Recommended Phase II Dose
For the Phase I component, no formal statistical analysis was planned. The primary endpoint is to determine the maximum tolerated dose (MTD) and recommended Phase II dose of lenalidomide given in combination with standard idarubicin + cytarabine induction therapy. (NCT00831766)
Timeframe: 18 months
| Intervention | mg/day (Number) |
|---|
| Phase I Participants | 20 |
Phase II: Complete Response Rate of Participants Treated at Maximum Tolerated Dose (MTD)
Percentage of participants achieving CR/CRi. Complete Response (CR) plus Complete Response with Incomplete Count Recovery (CRi) rates. Response rates (CR + CRi) of lenalidomide following idarubicin and cytarabine induction therapy in older patients with previously untreated AML. A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. CRi: After chemotherapy, patients fulfill all of the criteria for CR except for residual neutropenia (1,000/μL) or thrombocytopenia (100,000/μL). (NCT00831766)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| All Participants Treated at MTD | 54 |
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
The length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease (NCT00837031)
Timeframe: 18 months
| Intervention | months (Median) |
|---|
| Lenalidomide/Gemcitabine | 2.3 |
Six-Month Overall Survival (OS) Probability, the Percentage of Patients Estimated to be Alive Six Months After Beginning Protocol Treatment
The percentage of patients who were alive 6 months after beginning treatment (NCT00837031)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide/Gemcitabine | 37 |
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Length of time, in months, that patients were alive from their first date of protocol treatment until death (NCT00837031)
Timeframe: 18 months
| Intervention | months (Median) |
|---|
| Lenalidomide/Gemcitabine | 4.7 |
Time to Major Erythroid Response (MER)
"Time to major erythroid response (MER) is defined in responders as the time from randomization to the documented date of MER.~For transfusion independent patients, the date of MER is the first date of the elevation in hemoglobin level of more than 2 g/dL that has been sustained for at least 8 weeks. For transfusion dependent patients, the date of MER is the beginning date of the time interval of transfusion independence that has been sustained for at least eight weeks." (NCT00843882)
Timeframe: Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
| Intervention | months (Median) |
|---|
| Arm A (Lenalidomide; Randomization) | 3.6 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 3.7 |
Proportion of Patients With Minor Erythroid Response
The definition of minor erythroid response: the mean hemoglobin is sustained 1.0 to 2.0 g/dL above the baseline value for a minimum of 8 weeks; or a 50% or greater decrease in 8-week red blood cell transfusion requirements compared to baseline. (NCT00843882)
Timeframe: Assessed every cycle during treatment and after completion of 16 weeks of treatment
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Randomization) | 0.208 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 0.182 |
Proportion of Patients With Major Erythroid Response (MER) to Salvage Combination Therapy
Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients. (NCT00843882)
Timeframe: Assessed after completion of 16 weeks of treatment
| Intervention | proportion of participants (Number) |
|---|
| Arm B (Lenalidomide + Epoetin Alfa; Crossover) | 0.25 |
Proportion of Patients With Major Erythroid Response (MER) Among Those With Chromosome 5q31.1 Deletion
Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients. (NCT00843882)
Timeframe: Assessed after completion of 16 weeks of treatment
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Chromosome 5q31.1 Deletion) | 0.632 |
Proportion of Patients With Major Erythroid Response (MER)
Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients. (NCT00843882)
Timeframe: Assessed after completion of 16 weeks of treatment
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Randomization) | 0.115 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 0.283 |
Proportion of Patients With Cytogenetic Response
"Evaluation of cytogenetic response requires 20 analyzable metaphases when using conventional techniques. Analysis of data will require 20 metaphases before and after treatment, which must be done on bone marrow only (peripheral blood is not a substitute). Fluorescent in situ hybridization (FISH) may be used as a supplement to follow a specifically defined cytogenetic abnormality, but it is not a substitute for conventional cytogenetic studies. Cytogenetic response is defined as follows: Complete response: Restoration of a normal karyotype in patients with a documented pre-existing clonal (>2 metaphases abnormal) chromosome abnormalities.~Partial response: > 50% reduction in the percentage of bone marrow metaphases with only clonal abnormality." (NCT00843882)
Timeframe: Assessed at baseline and after completion of 16 weeks of treatment
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Randomization) | 0.07 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 0.10 |
Proportion of Patients With Bone Marrow Response
"Bone marrow response includes complete remission (CR) and partial remission (PR).~Complete remission (CR): Bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia. When erythroid precursors constitute < 50% of bone marrow nucleated cells, the percent of blasts is based on all nucleated cells; when there are ≥ 50% erythroid cells, the percent blasts should be based on the non-erythroid cells.~Partial remission (PR): All of the CR criteria (if abnormal prior to treatment), except blasts decreased by 50% over pre-treatment, or a less advanced Myelodysplastic Syndromes (MDS) World Health Organization (WHO) classification than pretreatment. Cellularity and morphology are not relevant." (NCT00843882)
Timeframe: Assessed at 16 weeks
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Randomization) | 0.01 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 0.03 |
Pretreatment Endogenous Erythropoietin Level
"Pretreatment endogenous erythropoietin level was assessed at baseline. The association between pretreatment endogenous erythropoietin level and major erythroid response was evaluated among patients who received lenalidomide alone.~Major erythroid response is defined as transfusion-independence for ≥ 8 consecutive weeks for patients who were red blood cell transfusion-dependent at baseline AND a ≥ 1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value; or a > 2 g/dL rise in hemoglobin without transfusion for non-transfusion dependent patients." (NCT00843882)
Timeframe: Assessed at baseline and after completion of 16 weeks of treatment
| Intervention | mU/mL (Median) |
|---|
| Arm A Patients With Major Erythroid Response | 514.5 |
| Arm A Patients Without Major Erythroid Response | 150 |
Duration of Major Erythroid Response (MER)
Duration of major erythroid response (MER) is defined as the time interval between the documented date of MER and the earliest date of resumption of red blood cell transfusions ≥ 2 units in an 8-week period, a reduction in hemoglobin concentration ≥ 2 g/dL in the absence of acute infection, gastrointestinal bleeding and hemolysis, or death. (NCT00843882)
Timeframe: Assessed every cycle during treatment and then 3 and 6 months after last protocol treatment
| Intervention | months (Median) |
|---|
| Arm A (Lenalidomide; Randomization) | 13 |
| Arm B (Lenalidomide + Epoetin Alfa; Randomization) | 23.8 |
Complete Response Rate
Response assessments were made per the NCI working group criteria for CLL (Hallek et al, Blood, 2008). Complete response rate is defined as an achievement of all of the following: Peripheral blood lymphocytes (evaluated by blood and differential count) below 4 × 109/L (4000/μL), absence of significant lymphadenopathy (lymph nodes must be < 1.5 cm), absence of splenomegaly and hepatomegaly, absence of constitutional symptoms, normal blood counts, and bone marrow sample must be at least normocellular for age, with less than 30% of nucleated cells being lymphocytes. Lymphoid nodules should be absent. (NCT00860457)
Timeframe: 3 years
| Intervention | percentage of patients (Number) |
|---|
| Chemotherapy | 36 |
Response Rate
Number of participants with a complete or partial response according to International Working Group 2006 criteria. (NCT00867308)
Timeframe: 15 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Complete response | Partial response |
|---|
| Lenalidomide 15 mg | 0 | 0 |
,| Lenalidomide 50 mg | 0 | 2 |
Grade 3-4 Toxicity
Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide. (NCT00867308)
Timeframe: Up to 8 months
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide 15 mg | 6 |
| Lenalidomide 50 mg | 12 |
Maximum Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -10.9 |
| Investigators Choice | -2.3 |
Maximum Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain to Treatment Scale was scored between 0 and 100, with a higher score representing a higher quality of life. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 4.6 |
| Investigators Choice | 5.6 |
Maximum Change From Baseline in the EORTC QLQ-C30 Insomnia Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -12.8 |
| Investigators Choice | -7.6 |
Maximum Change From Baseline in the EORTC QLQ-C30 Nausea and Vomiting Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Scale was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -2.3 |
| Investigators Choice | -0.6 |
Maximum Change From Baseline in the EORTC QLQ-C30 Pain Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -5.8 |
| Investigators Choice | -3.5 |
Maximum Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 3.4 |
| Investigators Choice | -1.8 |
Maximum Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 3.1 |
| Investigators Choice | 5.0 |
Maximum Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 5.1 |
| Investigators Choice | 3.8 |
Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review
Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response (CR), Complete Response unconfirmed (CRu) or Partial Response (PR). Participants who discontinued before any response had been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide | 40.0 |
| Investigators Choice | 10.7 |
Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis
Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide | 45.9 |
| Investigators Choice | 22.6 |
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review
Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide | 69.4 |
| Investigators Choice | 63.1 |
Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis
Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass >1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses. Stable disease (SD) is defined as less than a PR (see above) but is not progressive disease or relapsed disease. (NCT00875667)
Timeframe: From date of randomization to the discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
| Intervention | Percentage of participants (Number) |
|---|
| Lenalidomide | 70.0 |
| Investigators Choice | 65.5 |
Mean Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 16.2 | -0.8 | 5.1 | -12.5 | -11.1 | 5.4 |
,| Lenalidomide | 18.1 | 2.5 | 1.9 | -2.3 | -4.3 | 4.8 |
Mean Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 83.6 | -2.3 | 1.3 | 4.2 | 5.6 | -2.3 |
,| Lenalidomide | 84.6 | 0.0 | -1.9 | -3.2 | -2.5 | -5.1 |
Mean Change From Baseline in the EORTC QLQ-C30 Constipation
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 8.6 | -0.8 | 1.3 | 0.0 | 0.0 | 0.8 |
,| Lenalidomide | 12.5 | 6.3 | 4.2 | 3.5 | -0.7 | 10.2 |
Mean Change From Baseline in the EORTC QLQ-C30 Diarhoea
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarhoea Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 12.6 | -3.1 | 1.3 | -4.2 | 0.0 | 0.0 |
,| Lenalidomide | 15.7 | -3.5 | -4.2 | 2.4 | -2.1 | 1.6 |
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain was scored between 0 and 100, with a high score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 21.2 | -0.8 | 0.0 | 4.2 | 5.6 | 0.8 |
,| Lenalidomide | 26.5 | -1.6 | -1.4 | -2.9 | 1.4 | 6.0 |
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 39.2 | 2.1 | 3.4 | -6.9 | -7.4 | 2.6 |
,| Lenalidomide | 40.2 | 0.1 | -3.2 | -1.0 | -3.9 | 5.2 |
Mean Change From Baseline in the EORTC QLQ-C30 Financial Problems Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Problems Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 10.8 | -0.8 | -3.8 | -4.2 | -5.6 | 1.6 |
,| Lenalidomide | 19.5 | -7.0 | -7.0 | -2.9 | -9.2 | -4.3 |
Maximum Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 3.2 |
| Investigators Choice | 2.9 |
Mean Change From Baseline in the EORTC QLQ-C30 Insomnia Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 25.7 | -4.7 | -6.4 | -16.7 | -16.7 | 0.8 |
,| Lenalidomide | 29.4 | -7.6 | -5.2 | -1.8 | -7.1 | -3.2 |
Mean Change From Baseline in the EORTC QLQ-C30 Nausea / Vomiting Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea and Vomiting Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 3.8 | 0.4 | 5.8 | 2.1 | 2.8 | 6.6 |
,| Lenalidomide | 4.9 | 2.5 | 2.6 | 5.3 | -0.7 | 0.5 |
Mean Change From Baseline in the EORTC QLQ-C30 Pain Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Domain was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Cycle 3 Day 1 | Cycle 5 Day 1 | Cycle 7 Day 1 | Cycle 9 Day 1 | Treatment Discontinuation |
|---|
| Investigators Choice | 13.7 | -1.2 | -2.6 | 0.0 | -2.8 | 3.5 |
,| Lenalidomide | 22.6 | -2.2 | -0.2 | 3.2 | -3.2 | 4.6 |
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 78.9 | -3.7 | -2.1 | 4.2 | 11.1 | -5.1 |
,| Lenalidomide | 71.8 | -0.5 | 1.6 | 2.4 | 2.8 | -5.6 |
Mean Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 78.4 | -1.2 | -4.5 | 2.1 | 0.0 | -2.7 |
,| Lenalidomide | 74.9 | -1.0 | 1.6 | -1.5 | 4.3 | -5.1 |
Number of Participants With Treatment Emergent Adverse Events
Adverse events were assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3: according to the following scale: Grade 1 = Mild Adverse Event (AE), Grade 2 = Moderate AE, Grade 3 = Severe and Undesirable AE, Grade 4 = Life-threatening or Disabling AE, and Grade 5 = Death; Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. after the first dose of study drug and within 28 days after the last dose. A Treatment Emergent Adverse event (TEAE) is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. (NCT00875667)
Timeframe: From the date of the first dose of study drug to 28 days after the last dose, up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any TEAE Grade 3 AE | Any TEAE Grade 4 AE | Any TEAE Grade 5 AE | Any TEAE Related to the IP | Any Grade 3 AE Related to IP | Any Grade 4 AE Related to IP | Any Grade 5 AE Related to IP | Any Serious Adverse Event (SAE) | Any SAE Related to IP | Any TEAE Leading to Stopping of IP | Any Treatment Related AE Leading to Stopping IP | TEAE Leading to Dose Reduction/Interruption | Related AE Leading to Dose Reduct/Interruption | TEAE Leading to Dose Reduction | Related AE Leading to Dose Reduction | TEAE Leading to Dose Interruption | Related AE Leading to Dose Interruption |
|---|
| Investigators Choice | 69 | 49 | 29 | 2 | 51 | 36 | 19 | 0 | 22 | 12 | 14 | 7 | 33 | 29 | 13 | 10 | 28 | 25 |
,| Lenalidomide | 159 | 126 | 56 | 15 | 141 | 106 | 46 | 0 | 75 | 38 | 31 | 18 | 114 | 103 | 72 | 69 | 110 | 98 |
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Domain ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 78.5 | 1.3 | 1.3 | -3.1 | 1.4 | -1.5 |
,| Lenalidomide | 73.7 | 3.4 | 3.6 | 8.1 | 4.5 | -1.3 |
Mean Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 73.9 | 3.5 | -6.4 | 0.0 | 13.9 | -4.3 |
,| Lenalidomide | 71.5 | -4.8 | 1.4 | 0.3 | 1.8 | -9.1 |
Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review
Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 69.6 |
| Investigators Choice | 45.1 |
Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis
Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 70.1 |
| Investigators Choice | 91.7 |
Kaplan Meier Estimate for Overall Survival (OS) According to the IRC Central Review
Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; overall median follow-up was 93.9 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 121.0 |
| Investigators Choice | 91.7 |
Kaplan Meier Estimate for Overall Survival as Assessed by the Investigator at the Final Analysis
Overall survival was defined as the time from randomization until death from any cause. Participants alive or lost to follow-up at the time of analysis were censored at the last date they were known to be alive. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to the study discontinuation date of 09 October 2018; overall median follow-up time was 285 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 120.6 |
| Investigators Choice | 91.7 |
Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review
PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 37.6 |
| Investigators Choice | 22.7 |
Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis
Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment. (NCT00875667)
Timeframe: From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 37.3 |
| Investigators Choice | 23.6 |
Kaplan Meier Estimate of Time to First Response (TTFR) According to the IRC Central Review
Time to Response was defined as the time from first dose of study drug to the date of the first response (having at least a PR) and was calculated only for responding participants. ). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From randomization of study drug to time of first documented PR or better response; up to data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 18.7 |
| Investigators Choice | NA |
Kaplan Meier Estimate of Time to First Response as Assessed by the Investigator at the Final Analysis
Time to first response was defined as the time from first dose of study drug to the date of the first response (having at least a PR). Participants with progression at the time of analysis were censored at the first assessment date that the participant was known to have progressed. Participants with SD at the time of analysis were censored at the last assessment date that the subject was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 23.9 |
| Investigators Choice | 40.0 |
Kaplan Meier Estimate of Time to Progression According to the IRC Central Review
Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 39.3 |
| Investigators Choice | 24.7 |
Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis
Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free. (NCT00875667)
Timeframe: From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 39.3 |
| Investigators Choice | 24.7 |
Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator
Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. (NCT00875667)
Timeframe: From the date of the first treatment to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 24.4 |
| Investigators Choice | 17.9 |
Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis
Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake. (NCT00875667)
Timeframe: From date of first dose of treatment to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 24.4 |
| Investigators Choice | 17.9 |
Maximum Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -4.8 |
| Investigators Choice | -4.1 |
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status / QoL Domain
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status / QoL Domain was scored between 0 and 100, with a higher score representing a higher quality of life. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 3 Day 1 | Change from Baseline to Cycle 5 Day 1 | Change from Baseline to Cycle 7 Day 1 | Change from Baseline to Cycle 9 Day 1 | Change from Baseline to Treatment Discontinuation |
|---|
| Investigators Choice | 58.4 | 2.3 | 3.2 | 7.3 | 8.3 | -1.0 |
,| Lenalidomide | 59.0 | -3.4 | -0.7 | 1.0 | 4.3 | -5.8 |
Maximum Change From Baseline in the EORTC QLQ-C30 Constipation Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -0.3 |
| Investigators Choice | -3.5 |
Maximum Change From Baseline in the EORTC QLQ-C30 Diarhoea Domain to Treatment Discontinuation Visit
"The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).~The EORTC QLQ-C30 Diarhoea Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement." (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and time of discontinuation from treatment visit.Up to final data cut-0ff date of 07 March 2014
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Lenalidomide | -7.2 |
| Investigators Choice | -5.8 |
Maximum Change From Baseline in the EORTC QLQ-C30 Dyspnoea Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Domain to Treatment Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -7.3 |
| Investigators Choice | -5.8 |
Maximum Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale ranges from 0 to 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | 6.9 |
| Investigators Choice | 3.7 |
Maximum Change From Baseline in the EORTC QLQ-C30 Fatigue Domain to Treatment Discontinuation Visit
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale was scored between 0 and 100, with a higher score representing worse symptomatic expression. (NCT00875667)
Timeframe: Baseline known as screening visit, after cycle 2 (C3D1), after Cycle 4 (C5D1), after Cycle 6, (C7D1), after Cycle 8, (C9D1) and at discontinuation; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm.
| Intervention | units on a scale (Mean) |
|---|
| Lenalidomide | -4.9 |
| Investigators Choice | -2.9 |
Event-free Survival (EFS)
Assessed as the median value for EFS 12 months after starting MDR treatment (NCT00890552)
Timeframe: 12 months
| Intervention | months (Median) |
|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | 3.15 |
Duration of Response
Assessed as the median value for the time from first partial response until progression; death; or last follow-up. (NCT00890552)
Timeframe: 32 months
| Intervention | months (Median) |
|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | 9.1 |
Overall Survival (OS)
Participants alive 12 months after starting MDR treatment. (NCT00890552)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | 58 |
Hematologic Response Rate
At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L); or partial response (dFLC decrease > 50%). (NCT00890552)
Timeframe: 8 weeks
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Very good Partial Response (VGPR) | Partial Response (PR) | No Response (NR) | Response not evaluable |
|---|
| Lenalidomide, Melphalan and Dexamethasone (MDR) | 2 | 4 | 8 | 9 | 1 |
Time to CR
CR includes subjects with CR but incomplete recovery of blood counts (CRi). Responses were assessed according to the ELN guidelines. (NCT00890929)
Timeframe: 18 weeks
| Intervention | weeks (Median) |
|---|
| Azacitidine Followed by Lenalidomide | 12 |
Maximum Tolerated Dose (MTD) of Lenalidomide
The maximum tolerated dose (MTD) of lenalidomide was determined in study phase 1, for use in study Phase 2 (not conducted). The outcome is reported as the dose of lenalidomide that represents the MTD. (NCT00890929)
Timeframe: 15 months
| Intervention | mg/day lenalidomide (oral) (Number) |
|---|
| Azacitidine Followed by Lenalidomide | 50 |
Remission Duration
Responses and remission were assessed according to the ELN guidelines. (NCT00890929)
Timeframe: 26 months
| Intervention | weeks (Median) |
|---|
| Azacitidine Followed by Lenalidomide | 6 |
OS of Responders
OS from the start of treatment of responders (per ELN guidelines) was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012. (NCT00890929)
Timeframe: 88 weeks (median)
| Intervention | weeks (Median) |
|---|
| Azacitidine Followed by Lenalidomide | 69 |
Overall Response Rate (ORR)
ORR includes subjects with CR, CRi, and partial response (PR). Responses were assessed according to the ELN guidelines. (NCT00890929)
Timeframe: 26 months
| Intervention | percentage of subjects (Number) |
|---|
| Azacitidine Followed by Lenalidomide | 41 |
Overall Survival (OS)
OS from the start of treatment was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012. (NCT00890929)
Timeframe: 88 weeks (median)
| Intervention | weeks (Median) |
|---|
| Azacitidine Followed by Lenalidomide | 20 |
4-week Survival Rate
"Early death was assessed as death within 28 days of the start of treatment" (NCT00890929)
Timeframe: 28 days
| Intervention | percentage of subjects remaining alive (Number) |
|---|
| Azacitidine Followed by Lenalidomide | 83 |
Compete Remission (CR) Rate
Compete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood. (NCT00890929)
Timeframe: 12 months
| Intervention | percentage of subjects (Number) |
|---|
| Azacitidine Followed by Lenalidomide | 28 |
Time to PR
Responses were assessed according to the ELN guidelines. (NCT00890929)
Timeframe: 36 weeks
| Intervention | weeks (Median) |
|---|
| Azacitidine Followed by Lenalidomide | 6 |
Percentage of Participants With GVHD (Graft Versus Host Disease)
Acute grade 2 to 4 Graft versus host disease( GVHD )for patients who were able to be analyzed by measuring the T cell counts for increased CD3+ before and after lenalidomide. (NCT00899431)
Timeframe: Up to 6 months after allotransplant
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 | 0 |
| Group 2 | 3 |
| Group 3 | 1 |
Phase 2 - Number of Subjects Who Are Progression-Free and Alive
"Progression is defined as:~At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s)." (NCT00903630)
Timeframe: 3 months after starting treatment
| Intervention | participants (Number) |
|---|
| Lenalidomide With Liposomal Doxorubicin | 8 |
Phase 1 - Maximum Tolerated Dose (MTD) of Lenalidomide When Combined With Fixed Dose Liposomal Doxorubicin in Women With Recurrent Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
The maximum tolerated dose (MTD) reflects the highest dose of Lenalidomide when combined with fixed dose Liposomal Doxorubicin at which no more than one out of 6 participants experiences a dose limiting toxicity (DLT). (NCT00903630)
Timeframe: 1 cycle (28 days)
| Intervention | milligrams (mg) (Number) |
|---|
| Lenalidomide With Liposomal Doxorubicin | 10 |
Phase 1 - Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLT is defined as the inability to complete cycle 1 and/or begin cycle 2 within 7 days of the planned start due to a grade 4 or greater hemtologic toxicity or a grade 3 or greater non-hematologic toxicity. Grading was based on Common Toxicity Criteria (CTC) Version 4. (NCT00903630)
Timeframe: within 5 weeks of starting treatment
| Intervention | participants (Number) |
|---|
| Phase 1 - Dose Level 1 | 0 |
| Phase I - Dose Level 2 | 2 |
Phase 2 - Number of Subjects Achieving a Partial or Complete Response
"Partial response is defined as:~At least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. To be assigned a status of partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met.~Complete response is defined as:~The disappearance of all target lesions. To be assigned a status of complete response, changes in tumor measurements must be confirmed by repeat assessments performed no less than four weeks after the criteria for response are first met." (NCT00903630)
Timeframe: 3 months after starting treatment
| Intervention | participants (Number) |
|---|
| Phase 2 | 1 |
Phase 2 - Number of Subjects Who Are Progression-Free and Alive
"Progression is defined as:~At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurement, or the appearance of one or more new lesion(s)." (NCT00903630)
Timeframe: 6 months after starting treatment
| Intervention | participants (Number) |
|---|
| Lenalidomide With Liposomal Doxorubicin | 5 |
Overall Survival
Is defined as the time interval from start of treatment to the date of death due to any cause. In the absence of confirmation of death (including subjects lost to follow-up), survival time will be censored at the last date the subject is known to be alive (NCT00908232)
Timeframe: At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy. Further follow up by monthly phone call until the last patient was treated and followed for 1 year
| Intervention | days (Median) |
|---|
| Complete to Partial Response: Bortezomib + Dexamethasone | NA |
| Stable Disease After 4 Cycles: VD, VDC, VDL | NA |
Time to Progression
Is calculated as the time from start of treatment to the date of the first observation of disease progression or relapse from CR. Deaths owing to causes other than progression not counted, but censored. Subjects who withdraw from the study or die will be censored at the time of last disease assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). (NCT00908232)
Timeframe: At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR), Median Follow-up of 16.9 months
| Intervention | days (Median) |
|---|
| Complete to Partial Response: Bortezomib + Dexamethasone | 366.0 |
| Stable Disease After 4 Cycles: VD, VDC, VDL | 214.0 |
Progression Free Survival
"Time from start of treatment to date of disease progression, relapse from CR or death. Estimated using the kaplan-meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as accurate and appropriate." (NCT00908232)
Timeframe: At Day 1 of each treatment cycle, at the End of Treatment visit until there is evidence of Progressive Disease or relapse from Complete Response (CR). Median Follow-Up of 16.9 months
| Intervention | days (Median) |
|---|
| Complete to Partial Response: Bortezomib + Dexamethasone | 311.0 |
| Stable Disease After 4 Cycles: VD, VDC, VDL | 214.0 |
One Year Survival
Percent Probability of Survival at 1 year from the start of treatment, estimated using Kaplan-Meier analysis. (NCT00908232)
Timeframe: At each visit from baseline to end of treatment. After treatment, monthly visit until progression or relapse or until the start of alternative MMY therapy, up to 1 year
| Intervention | percent probability (Number) |
|---|
| Complete to Partial Response: Bortezomib + Dexamethasone | 80 |
| Stable Disease After 4 Cycles: VD, VDC, VDL | 89 |
Overall Best Confirmed Response
Overall Best Confirmed Response is the best Overall Response Rate with borezomib-dexamathasone (+/-cyclophosphamide or lenalidomide) recorded between baseline and end of treatment. Response was assessed using the International Myeloma working Group (IMWG) Uniform Response Criteria and validated by an Independent Monitoring Committee. (NCT00908232)
Timeframe: Prior to treatment at day 1 of each cycle and at the end of treatment (day 21 of cycle 8), up to 168 days
| Intervention | number of participants (Number) |
|---|
| Complete to Partial Response: Bortezomib + Dexamethasone | 101 |
| Stable Disease After 4 Cycles: VD, VDC, VDL | 6 |
PK Phase: Area-under-the Concentration-time Curve (AUC0-24) for Lenalidomide
Area under the plasma concentration-time curve from Time 0 to 24 hours post-dose for lenalidomide after a single dose, calculated using the log-linear trapezoidal method. (NCT00910858)
Timeframe: On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| 10 mg Lenalidomide | 817 |
Monotherapy Phase: Area-under-the Concentration-time Curve (AUC0-5) for Lenalidomide
Area under the plasma concentration-time curve from Time 0 to 5 hours postdose for lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days, calculated using the log-linear trapezoidal method. (NCT00910858)
Timeframe: On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 563 | 315 | 248 |
Monotherapy Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)
The Maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after multiple dosing for 14 days. (NCT00910858)
Timeframe: On Day 14 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, and 5 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 185 | 104 | 80.7 |
Percentage of Participants Overall With Erythroid Response by Baseline Erythropoietin Level
To evaluate the predictive value of pretreatment serum erythropoietin (EPO) concentration for erythroid response to lenalidomide, the percentage of erythroid responders versus non-responders were stratified by Baseline EPO levels (≤ 500 mIU/mL versus > 500 mIU/mL). Response includes participants with either a major or minor response. (NCT00910858)
Timeframe: Assessed every 28 days until study discontinuation (up to 1218 days)
| Intervention | percentage of participants (Number) |
|---|
| Baseline EPO ≤ 500 mIU/mL | Baseline EPO > 500 mIU/mL |
|---|
| Non-responders | 47.8 | 39.1 |
,| Overall | 53.8 | 38.5 |
,| Responders | 62.5 | 37.5 |
Percentage of Participants With a Erythroid Response Across All Phases
Erythroid response was categorized as either a major response or a minor response. A major response was defined as red blood cell (RBC) transfusion independence during any consecutive 56-day period and an increase in hemoglobin of at least 1.5 g/dL. A minor response was defined as a ≥ 50% or ≥ 4 unit decrease in RBC transfusions from pretreatment requirements (the number of RBC transfusions required over an 8-week period before the start of study drug treatment). (NCT00910858)
Timeframe: Assessed every 28 days until study discontinuation (up to 1218 days).
| Intervention | percentage of participants (Number) |
|---|
| Major response | Minor response |
|---|
| 10 mg Del 5q | 85.7 | 0 |
,| 10 mg Non-del 5q | 17.6 | 5.9 |
,| 15 mg Non-del 5q | 40.0 | 0 |
PK Phase: Maximum Plasma Concentration of Lenalidomide (Cmax)
The maximum observed plasma concentration (Cmax) of lenalidomide (its R- and S- enantiomers and the enantiomers combined) after a single dose on day -7. (NCT00910858)
Timeframe: On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 179 | 101 | 78.3 |
PK Phase: Percent of Administered Lenalidomide Excreted Over 24 Hours After a Single, Oral Dose
"Percent of the administered dose of lenalidomide excreted unchanged in urine over 24 hours postdose after a single dose on Day -7, calculated as:~(amount excreted unchanged in urine over 24 hours postdose / Dose) * 100.~The dose was 10 mg for total lenalidomide and 5 mg for the enantiomers." (NCT00910858)
Timeframe: On Day -7 at predose and over the intervals of 0-5, 5-8, 8-12, and 12-24 hours postdose.
| Intervention | percent of administered dose (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 65.1 | 67.9 | 62.2 |
PK Phase: Terminal Half-life (t1/2)
The apparent terminal half-life is the time required for plasma concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached, and calculated as the natural logarithm of 2 (0.693) / Apparent terminal rate constant (λz). (NCT00910858)
Timeframe: On Day -7 blood samples were taken at predose (0 hour), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 3.72 | 4.14 | 3.58 |
Monotherapy Phase: Percent of Lenalidomide Excreted Over 5 Hours Post Day 14 Dose
"Percent of the administered lenalidomide dose excreted unchanged in urine over 5 hours postdose after multiple dosing for 14 days, calculated as:~(amount excreted unchanged in urine over the first 5 hours postdose / Dose) * 100.~The dose was 10 mg for total lenalidomide and 5 mg for the enantiomers." (NCT00910858)
Timeframe: On Day 14, at predose and over the interval of 0-5 hours postdose.
| Intervention | percent of administered dose (Geometric Mean) |
|---|
| Total Lenalidomide | S-Lenalidomide | R-Lenalidomide |
|---|
| 10 mg Lenalidomide | 34.0 | 35.4 | 32.5 |
Time to Grade 4 Neutropenia or Thrombocytopenia
Time to the first event of grade 4 neutropenia or thrombocytopenia, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0, was calculated as date of first event - date of first dose + 1. (NCT00910858)
Timeframe: From the date of first dose until 30 days after the last dose (up to 1218 days)
| Intervention | days (Median) |
|---|
| Grade 4 Neutropenia | Grade 4 Thrombocytopenia |
|---|
| Del 5q | 28.0 | 29.0 |
,| Non-del 5q | 69.0 | 53.0 |
Number of Participants With Adverse Events With a Later Cut-off Date of 31 March 2014
AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death (NCT00910910)
Timeframe: From randomization to the data cut-off date of 31 March 2014; Up to 53 months; maximum duration of exposure for Lenalidomide was 1140 days and 406 days for Chlorambucil
| Intervention | participants (Number) |
|---|
| ≥ 1 TEAE | ≥ 1 TEAE related to study drug | ≥ 1 NCI CTC Grade 3-4 TEAE | Grade 3-4 adverse event related to any study drug | ≥ 1 NCI CTC Grade 5 TEAE | ≥ Grade 5 adverse event related to any study drug | ≥ 1 Serious TEAE | ≥ 1 Serious TEAE related to any study drug | ≥1 TEAE leading to stopping either study drug | ≥1 Related TEAE leading to stopping either drug |
|---|
| Chlorambucil | 202 | 155 | 131 | 90 | 11 | 1 | 90 | 53 | 42 | 23 |
,| Lenalidomide | 216 | 194 | 188 | 157 | 21 | 6 | 148 | 107 | 70 | 46 |
Number of Participants With Adverse Events (AEs)
AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death (NCT00910910)
Timeframe: From randomization up to data cut-off of 18 Feb 2013; Up to approximately 39 months; maximum duration of exposure for Lenalidomide was 1086 days and 406 days for Chlorambucil
| Intervention | participants (Number) |
|---|
| ≥ 1 TEAE | ≥ 1 TEAE related to study drug | ≥ 1 NCI CTC Grade 3-4 TEAE | Grade 3-4 adverse event related to any study drug | ≥ 1 NCI CTC Grade 5 TEAE | ≥ Grade 5 adverse event related to any study drug | ≥ 1 Serious TEAE | ≥ 1 Serious TEAE related to any study drug | ≥1 TEAE leading to stopping either study drug | ≥1 Related TEAE leading to stopping either drug |
|---|
| Chlorambucil | 186 | 139 | 117 | 82 | 9 | 1 | 76 | 46 | 34 | 19 |
,| Lenalidomide | 202 | 183 | 173 | 143 | 21 | 6 | 129 | 95 | 61 | 39 |
Number of Participants and Types of Subsequent Anti-cancer Therapies Received Post Treatment
Subsequent anti-cancer therapies administered to participants following the discontinuation of study drug (either Lenalidomide or Chlorambucil) (NCT00910910)
Timeframe: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
| Intervention | participants (Number) |
|---|
| Participants receiving additional CLL therapy | Participants receiving alkylating agents | Participants receiving antineoplastic aents | Participants receiving antimetabolites | Participants receiving corticosteroids | Participants receiving plant alkaloids | Participants receiving cytotoxic antibiotics | Participants receiving immunosuppressants | Participants receiving therapeutic products | Participants receiving other unspecified products | Antihistamine For Systemic Use | Drugs for Peptic ulcer and Gastric Reflex | Immunoglobulins | Other Analgesics and Antipyretics | Specific Antirheumatic Agents | Antiemetics and Antinauseants | Corticosteriods for Systemic Use | Immunostimulants |
|---|
| Chlorambucil | 120 | 106 | 86 | 24 | 16 | 11 | 3 | 2 | 3 | 2 | 1 | 0 | 2 | 1 | 0 | 1 | 1 | 1 |
,| Lenalidomide | 125 | 107 | 93 | 34 | 27 | 22 | 10 | 3 | 4 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 |
Time to Response
Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines (NCT00910910)
Timeframe: Up to data cut-off of 18 Feb 2013; up to approximately 39 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 8.6 |
| Chlorambucil | 8.1 |
Percentage of Participants With the Best Overall Response Based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines
"A best overall response rate is a CR, CRi, nPR or PR and is defined as:~Complete Remission (CR):~No lymphadenopathy~No hepatomegaly or splenomegaly~Absence of constitutional symptoms~Polymorphonuclear leukocytes ≥ 1500/ul~No circulating clonal B-lymphocytes~Platelets > 100,000/ul~Hemoglobin > 11.0 g/dl~Normocellular <30% lymphocytes, no B-lymphoid nodules;~Incomplete Clinical Response (CRi):~• CR without bone marrow biopsy confirmation.~Nodular Partial Response (nPR):~• CR with the presence of residual clonal nodules.~Partial Response (PR) requires:~≥ 50% decrease in peripheral blood lymphocyte count~≥ 50% reduction in lymphadenopathy~≥ 50% reduction in size of liver and/or spleen~1 or more of the following:~Polymorphonuclear leukocytes ≥ 1500/ul~Platelets >100,000/ul" (NCT00910910)
Timeframe: Up to data cut-off date of 18 Feb 2013; approximately 39 months
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 51.9 |
| Chlorambucil | 62.3 |
Percentage of Participants With a Best Overall Response Based on IWCLL Guidelines With a Later Cut-off Date of 31 March 2014
"A best overall response rate is a CR, CRi, nPR or PR and is defined as:~Complete Remission (CR):~No lymphadenopathy~No hepatomegaly or splenomegaly~Absence of constitutional symptoms~Polymorphonuclear leukocytes ≥ 1500/ul~No circulating clonal B-lymphocytes~Platelets > 100,000/ul~Hemoglobin > 11.0 g/dl~Normocellular <30% lymphocytes, no B-lymphoid nodules;~Incomplete Clinical Response (CRi):~• CR without bone marrow biopsy confirmation.~Nodular Partial Response:~• CR with the presence of residual clonal nodules.~Partial Response requires:~≥ 50% decrease in peripheral blood lymphocyte count~≥ 50% reduction in lymphadenopathy~≥ 50% reduction in size of liver and/or spleen~1 or more of the following:~Polymorphonuclear leukocytes ≥ 1500/ul~Platelets >100,000/ul" (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; approximately 53 months
| Intervention | percentage of participants with response (Number) |
|---|
| Lenalidomide | 60.9 |
| Chlorambucil | 70.2 |
Kaplan Meier Estimate of Overall Survival
Overall Survival is defined as the time between randomization and death from any cause. (NCT00910910)
Timeframe: Up to data cut off of 31 March 2014; median follow-up for all participants was 18.8 months
| Intervention | Months (Median) |
|---|
| Lenalidomide | NA |
| Chlorambucil | 44.0 |
Kaplan-Meier Estimate for Duration of Response
Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had withdrawn consent or were lost to follow-up prior to documentation of progression (NCT00910910)
Timeframe: Up to data cut-off of 18 Feb 2013; up to approximately 39 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide | NA |
| Chlorambucil | 105.3 |
Time to Response for a Later Cut-off Date of 31 March 2014
Time to response was calculated as the time from randomization to the first nPR, PR, CRi or CR based on IWCLL guidelines (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; up to approximately 53 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 10.4 |
| Chlorambucil | 8.1 |
Kaplan-Meier Estimate for Duration of Response With a Later Cut-off Date of 31 March 2014
Duration of response was defined as the time from first nPR, PR, CRi, or CR to PD. Duration of response was censored at the last date that the patient was known to be progression-free for: 1) patients who had not progressed at the time of analysis; 2) patients who had withdrawn consent or were lost to follow-up prior to documentation of progression (NCT00910910)
Timeframe: Up to data cut-off of 31 March 2014; up to approximately 53 months
| Intervention | weeks (Median) |
|---|
| Lenalidomide | NA |
| Chlorambucil | 87.1 |
Kaplan-Meier Estimate of Progression Free Survival (PFS)
Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression (NCT00910910)
Timeframe: From first dose of study drug to date of data cut-off of 18 Feb 2013; up to approximately 39 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 30.8 |
| Chlorambucil | 23.0 |
Kaplan Meier Estimate for Overall Survival at the Final Analysis
Overall Survival is defined as the time between randomization and death from any cause. Overall survival was censored at the last date that the subject was known to be alive for participants who were alive as of the data cutoff date and for participants who were lost to follow-up before death was documented. (NCT00910910)
Timeframe: Up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
| Intervention | Months (Median) |
|---|
| Lenalidomide | 74.3 |
| Chlorambucil | 70.5 |
Kaplan-Meier Estimate of Progression Free Survival (PFS) With a Later Cut-off Date of 14 March 2014
Progression-free survival was defined as the time from randomization to the first documented progression confirmed per investigator's assessment or death due to any cause on study, whichever occurred first. Progressive disease included lymphadenopathy, an appearance of any new lesion such as enlarged lymph nodes (> 1.5 cm), splenomegaly, hepatomegaly or other organ infiltrates, an increase by 50% or more in greatest determined diameter of any previous site or an increase by 50% or more in the sum of the product of diameters of multiple nodes. The progression date was assigned to the earliest time when any progression was observed without prior missing assessments. If withdrawal of consent or lost to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00910910)
Timeframe: From randomization to data cut off date of 31 March 2014; median follow up time for all participants was 12.6 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 30.8 |
| Chlorambucil | 21.4 |
Number of Participants Deaths During the Treatment and Survival Follow-Up Phase
The number of study participants deaths during the treatment and follow-up phase (NCT00910910)
Timeframe: From the first dose of study drug up to the last patient last visit date of 19 May 2018; median follow-up for all participants was 46.7 months
| Intervention | Participants (Number) |
|---|
| Lenalidomide | 101 |
| Chlorambucil | 95 |
Kaplan-Meier Estimates of Duration of Response (DoR)
Duration of response was defined as the time from the first observation of a response (CR, RR or PR) to the first documented disease progression or relapse. For participants who did not progress during the study, duration of response was censored at the last adequate response assessment showing evidence of no disease progression. Disease progression is defined as an increase in M-protein serum monoclonal paraprotein and/or urine paraprotein or evidence of bone marrow plasmacytosis and plasma cells, an appearance of new or existing soft tissue plasmacytomas, an appearance of new or existing lytic bone lesions and/or hypercalcemia >11.5mg/dL (NCT00928486)
Timeframe: From the time of the first dose of study drug to study completion; the median duration on study was 42.1 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide and Dexamethasone | NA |
Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
A TEAE was defined as any AE that started on or after the first dose of study drug, and within End of Study (EOS) (28 days after the last dose of study drug received). A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; or constitutes an important medical event. The intensity of AEs were graded 1 to 5 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild grade (Grade 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4) or death (grade 5) (NCT00928486)
Timeframe: Day 1 of study drug through 28 days after the last dose of study drug; maximum treatment duration was 60.3 weeks
| Intervention | participants (Number) |
|---|
| Any Adverse Event (AE) | Drug-Related AE | Grade 3-4 Adverse Event | Drug-Related Grade 3-4 AE | Serious Adverse Event (SAE) | Drug-Related SAE | AE Leading to Study Drug Discontinuation | Related AE Leading to Len/Dex Discontinuation | AE leading to dose reduction or interruption | Related AE leading to dose reduction/interruption |
|---|
| Lenalidomide and Dexamethasone | 25 | 25 | 22 | 21 | 12 | 9 | 4 | 2 | 17 | 16 |
Myeloma Response Rate
Overall myeloma response rate was determined by the investigator using the Myeloma Response Determination Criteria adapted from Bladé criteria. A responder is any patient who showed at least a partial response. Overall myeloma response rate is defined as the percentage of participants who achieved a Complete Response (CR), plus a Remission Response (RR), plus a Partial Response (PR). A CR is the disappearance of monoclonal paraprotein and maintained for ≥ 6 weeks. RR is a 75-99% reduction in the level of the serum monoclonal paraprotein compared to baseline; 90-99% reduction in 24-hr urinary light chain excretion. PR is a 50-74% reduction in the level of monoclonal paraprotein compared to baseline; 50-89% reduction in 24-hr urinary light chain excretion. (NCT00928486)
Timeframe: From the time of the first dose of study drug to study completion; median duration on study was 42.1 weeks
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Dexamethasone | 62.5 |
RECIST-defined Measurable Disease
Patients who have a response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by RECIST criteria. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of SD, follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6-8 weeks (NCT00939510)
Timeframe: every 8 weeks and at end of treatment
| Intervention | participants (Number) |
|---|
| Number of patients with stable disease (SD) | Number of patients with partial response (PR) | Number of patients with progressive disease |
|---|
| Lenalidomide (Revlimid) and Sargramostim (GM-CSF) | 4 | 2 | 5 |
Number of Patients With Statistically Significant Change in Immune Response From Baseline to End of Study
The change in mean T cell immunohistochemical markers and dendritic cells over time will be evaluated using analysis of variance methods for repeated measures with additional main factors included in the analysis for subset comparisons. The pattern of immune response will be evaluated based upon overall clinical response using these same techniques. (NCT00939510)
Timeframe: every 28 days for first 3 cycles, end of study
| Intervention | participants (Number) |
|---|
| Lenalidomide (Revlimid) and Sargramostim (GM-CSF) | 0 |
Number of Patients With a PSA Response
Number of patients with a PSA Response defined as a PSA decline greater or equal to 50% compared with baseline value. (NCT00939510)
Timeframe: reevaluated for response every eight weeks
| Intervention | participants (Number) |
|---|
| PSA response | PSA no response |
|---|
| Lenalidomide (Revlimid) and Sargramostim (GM-CSF) | 4 | 27 |
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT00942578)
Timeframe: Date treatment consent signed to date off study, approximately 93 months and 22 days.
| Intervention | Participants (Count of Participants) |
|---|
| 15 mg Dose Lenalidomide | 14 |
| 20 mg Dose Lenalidomide | 3 |
| 25 mg Dose Lenalidomide | 46 |
Count of Participants With a Radiologic Response
Radiologic response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Confirmed radiologic PR | Complete Response | Stable Disease |
|---|
| 15 mg Lenalidomide | 3 | 0 | 1 |
,| 20 mg Lenalidomide | 2 | 2 | 0 |
,| 25 mg Lenalidomide | 20 | 0 | 3 |
Recommended Phase 2 Dose (RP2D)
The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide). (NCT00942578)
Timeframe: 3 weeks
| Intervention | mg (Number) |
|---|
| Single Arm - 4 Drug Combination | 25 |
Count of Participants With Dose-Limiting Toxicities (DLT)
DLT is defined as a ≥grade 3 non-hematological toxicity related to lenalidomide. (NCT00942578)
Timeframe: First 28 days of treatment.
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm - 4 Drug Combination | 0 |
Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells
Expression of TIM-3 on CD8 + T cells was evaluated by flow cytometry. (NCT00942578)
Timeframe: 46.5 months
| Intervention | Months (Median) |
|---|
| Low expression | High expression |
|---|
| 15 mg Lenalidomide | 23.6 | NA |
,| 20 mg Lenalidomide | NA | NA |
,| 25 mg Lenalidomide | 20.2 | 12.7 |
Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells
Expression of PD-1 on CD8 + T cells was evaluated by flow cytometry. High and low expression are based on the median values. Patients with a low expression of PD-1 proteins had better survival than those with a high expression. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Months (Median) |
|---|
| Low expression | High expression |
|---|
| 15 mg Dose Lenalidomide | 21.4 | 22.4 |
,| 20 mg Dose Lenalidomide | 17.8 | 26.1 |
,| 25 mg Dose Lenalidomide | 28.9 | 14.8 |
Count of Participants With Prostatic Antigen-Specific (PSA) Declines
PSA decline is defined as a ≥50% decline in measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as ≥10 mm with computed tomography, or ≥10 mm with calipers by clinical exam. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Participants with PSA>30% | Participants with PSA>50% | Participants with PSA>90% | Not Evaluable |
|---|
| 15 mg Lenalidomide | 13 | 12 | 5 | 1 |
,| 20 mg Lenalidomide | 3 | 3 | 1 | 0 |
,| 25 mg Lenalidomide | 41 | 40 | 27 | 1 |
Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration
The definition of an increase is any increase (any number greater than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. The definition of a decrease is any decrease (any number less than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. (NCT00942578)
Timeframe: After drug administration, an average of 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Increase in CAEC after 3 months | decrease in CAEC after 3 months |
|---|
| Single Arm - 4 Drug Combination | 30 | 20 |
Overall Response Rate (ORR)
ORR was defined as the percentage of patients with a complete response (CR), CR with incomplete bone marrow (BM) recovery (CRi) or partial response (PR) during treatment. Response was assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines. Per the guidelines, a CR required peripheral blood lymphocytes below 4 x 10^9/L, absence of lymphadenopathy, no hepatomegaly or splenomegaly, absence of disease and blood counts neutrophils >1.5 x 10^9/L, platelets >100 x 10^9/L, hemoglobin (hgb) >11g/dL) and BM at least normocellular for age. CRi = CR with incomplete BM recovery. PR = required at least 2 months from end of treatment, a ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value and either a ≥ 50% reduction in lymphadenopathy or ≥50% reduction of liver enlargement or ≥50% reduction of spleen enlargement plus neutrophils >1.5 x 10^9/ or ≥50% increase, platelets >100 x 10^9/L or ≥50% increase, hgb 11 g/dL. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide 5 mg | 47.1 |
| Lenalidomide 10 mg | 37.1 |
| Lenalidomide 15 mg | 40.0 |
Kaplan-Meier Estimate of Progression Free Survival
Progression-free survival (PFS) was calculated as the time from randomization to the first documented progression or death due to any cause during or after the treatment period, whichever occurred first. The progression date was assigned to the earliest time when any progression is observed without prior missing assessments. If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 31.4 |
| Lenalidomide 10 mg | 45.1 |
| Lenalidomide 15 mg | 66.3 |
Kaplan-Meier Estimate of Event-Free Survival
Event-free survival (EFS) is the interval between the start of treatment to the first sign of disease progression, or treatment for relapse or death (whichever occurred first). If withdrawal of consent or loss to follow-up occurred before documented progression or death, then these observations were censored at the date when the last complete tumor assessments determined a lack of progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 25.6 |
| Lenalidomide 10 mg | 31.9 |
| Lenalidomide 15 mg | 24.1 |
Kaplan-Meier Estimate of Duration of Response
Duration of response (DOR) was defined as the time from the first visit where PR, CRi, or CR was documented to progressive disease (PD). Duration of response was censored at the last date that the participant was known to be progression-free for participants who had not progressed at the time of analysis or who withdrew consent or were lost to follow-up prior to documentation of progression. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 101.1 |
| Lenalidomide 10 mg | 35.1 |
| Lenalidomide 15 mg | 88.8 |
Kaplan-Meier Estimate of Time to Progression
Time to progression (TTP) was defined as the time from randomization to the first documented progression. For participants who did not progress during the study, TTP was censored at the last adequate response assessment showing evidence of no disease progression. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 96.3 |
| Lenalidomide 10 mg | 47.6 |
| Lenalidomide 15 mg | 66.3 |
Kaplan-Meier Estimate of Overall Survival
Overall survival (OS) was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who had withdrawn consent or were lost to follow-up before death was documented. (NCT00963105)
Timeframe: From randomization until the end of the study; maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 161.0 |
| Lenalidomide 10 mg | 106.7 |
| Lenalidomide 15 mg | 154.6 |
Number of Participants With Treatment-emergent Adverse Events
Adverse events (AEs) were graded for severity by the investigator according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 with the exceptions of hematologic toxicities and tumor lysis syndrome, according to the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening or disabling AE Grade 5 = Death The investigator determined the relationship of each AE to study drug based on the timing of the AE and whether other medications, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the observed event. (NCT00963105)
Timeframe: From first dose of study drug to 30 days after the last dose; the maximum duration of treatment was 251, 265, and 267 weeks in the 5 mg, 10 mg, and 15 mg treatment groups respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Any adverse events | Treatment-related adverse events (TRAE) | Grade 3/4 adverse events | Treatment-related Grade 3/4 adverse events | Grade 5 adverse events | Treatment-related Grade 5 adverse events | Serious adverse events | Treatment-related serious adverse events | AE leading to discontinuation of study drug | TRAE leading to discontinuation of study drug | AE leading to study drug dose reduction only | AE leading to study drug dose interruption only | AE leading to study drug interruption & reduction |
|---|
| Lenalidomide 10 mg | 34 | 34 | 32 | 32 | 4 | 2 | 24 | 13 | 17 | 14 | 6 | 24 | 26 |
,| Lenalidomide 15 mg | 35 | 32 | 34 | 30 | 3 | 0 | 27 | 20 | 16 | 13 | 5 | 25 | 19 |
,| Lenalidomide 5 mg | 34 | 33 | 33 | 31 | 4 | 2 | 24 | 15 | 21 | 16 | 8 | 25 | 18 |
Time to Response
Time to response (TTR) was calculated as the time from randomization to the first documented date of response (PR, CRi or CR) based on iwCLL guidelines for participants with an objective response during the treatment period. (NCT00963105)
Timeframe: Response was assessed after 3 cycles of therapy (Week 12) and every 4 weeks thereafter until disease progression. Maximum time on study was 91 months.
| Intervention | weeks (Median) |
|---|
| Lenalidomide 5 mg | 16.9 |
| Lenalidomide 10 mg | 12.6 |
| Lenalidomide 15 mg | 12.7 |
Complete Response(CR) and Very Good Partial Response(VGPR)
To determine the best overall response (CR+VGPR+PR) of the lenalidomide, thalidomide, dexamethasone combination based on IMWG criteria at nadir. (NCT00966693)
Timeframe: Evaluated each 28-day cycle and nadir of criteria is considered best overall response (median time to best response for this study was 2 cycles (range for best overall response was 1-21 cycles).
| Intervention | Participants (Count of Participants) |
|---|
| Partial Remission | Progressive Disease | Very Good Partial Remission | Minimal Residual Disease | Stringent Complete Remission | Non Evaluable | Stable Disease |
|---|
| RTD (Cohort 1, Phase 1) | 2 | 0 | 0 | 0 | 0 | 1 | 0 |
,| RTD (Cohort 2, Phase 1) | 0 | 2 | 3 | 0 | 0 | 0 | 0 |
,| RTD (Cohort 2, Phase 2) | 13 | 6 | 8 | 9 | 3 | 7 | 7 |
,| RTD (Cohort 3, Phase 1) | 2 | 2 | 1 | 1 | 0 | 3 | 0 |
Incidence of Adverse Events
Linear regression was utilized to assess the effect of patient prognostic factors on the toxicity rate. (NCT00966693)
Timeframe: Up to 9 years
| Intervention | Participants (Count of Participants) |
|---|
| RTD (Cohort 1, Phase 1) | 0 |
| RTD (Cohort 2, Phase 1) | 0 |
| RTD (Cohort 3, Phase 1) | 2 |
| RTD (Cohort 2, Phase 2) | 10 |
Progression Free Survival
Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes. (NCT00966693)
Timeframe: Up to 9 years
| Intervention | Months (Mean) |
|---|
| RTD (Cohort 1, Phase 1) | 32.74 |
| RTD (Cohort 2, Phase 1) | 9.04 |
| RTD (Cohort 3, Phase 1) | 14.61 |
| RTD (Cohort 2, Phase 2) | 10.02 |
Number of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
To determine the dose limitations toxicities of the combination of lenalidomide and thalidomide and dexamethasone (LTD) in patients with relapsed/refractory multiple myeloma (RRMM). (NCT00966693)
Timeframe: After one 28-day cycle
| Intervention | Participants (Count of Participants) |
|---|
| RTD (Cohort 1, Phase 1) | 1 |
| RTD (Cohort 2, Phase 1) | 0 |
| RTD (Cohort 3, Phase 1) | 3 |
| RTD (Cohort 2, Phase 2) | 0 |
Time to Best Response
Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes. (NCT00966693)
Timeframe: Up to 9 years
| Intervention | months (Mean) |
|---|
| RTD (Cohort 1, Phase 1) | 19 |
| RTD (Cohort 2, Phase 1) | 5 |
| RTD (Cohort 3, Phase 1) | 5.16 |
| RTD (Cohort 2, Phase 2) | 3.3 |
Time to Progression
Time to Progression was estimated using Kaplan Meier analysis. (NCT00966693)
Timeframe: Up to 9 years
| Intervention | Months (Mean) |
|---|
| RTD (Cohort 1, Phase 1) | 32.74 |
| RTD (Cohort 2, Phase 1) | 9.04 |
| RTD (Cohort 3, Phase 1) | 14.61 |
| RTD (Cohort 2, Phase 2) | 10.02 |
Time to Next Therapy
Estimated using the method of Kaplan and Meier. (NCT00966693)
Timeframe: Up to 4.5 years
| Intervention | months (Median) |
|---|
| RTD (Cohort 1, Phase 1) | 52.4 |
| RTD (Cohort 2, Phase 1) | 14.3 |
| RTD (Cohort 3, Phase 1) | 10.5 |
| RTD (Cohort 2, Phase 2) | 6.47 |
Progression Free Survival
The primary endpoint of this study was progression-free survival (PFS), defined as the number of days from the day of first study drug administration to the day the patient experienced disease progression or death from any cause. Response and progression in cases of small lymphocytic lymphoma(SLL) were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of chronic lymphocytic leukemia (CLL) were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). (NCT00974233)
Timeframe: 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
| Intervention | months (Median) |
|---|
| Induction/Maintenance Chemotherapy | 18.3 |
Overall Survival
Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause. (NCT00974233)
Timeframe: 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
| Intervention | months (Median) |
|---|
| Overall Study Population | 42.8 |
Toxicities Observed With Induction Chemotherapy and Maintenance Therapy
Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0. (NCT00974233)
Timeframe: 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
| Intervention | participants (Number) |
|---|
| Grade 3 leukopenia | Grade 4 leukopenia | Grade 3 neutropenia | Grade 4 neutropenia | Grade 3 anemia | Grade 3 thrombocytopenia | Grade 4 thrombocytopenia | Grade 3 febrile neutropenia | Grade 3 infection | Grade 4 infection | Grade 5 infection | Grade 3 fatigue | Grade 4 fatigue | Grade 3 nausea/emesis | Grade 3 serum transaminase levels (Gr 3/Gr 4) |
|---|
| Induction Chemoimmunotherapy | 5 | 5 | 6 | 14 | 1 | 5 | 2 | 4 | 10 | 1 | 1 | 2 | 0 | 3 | 4 |
,| Maintenance | 6 | 1 | 7 | 2 | 0 | 1 | 0 | 1 | 4 | 1 | 0 | 0 | 1 | 0 | 0 |
Progression-free Survival
Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months. (NCT00974233)
Timeframe: 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
| Intervention | Proportion of participants (Median) |
|---|
| 1-year progression-free survival | 2-year progression-free survival | 3-year progression-free survival |
|---|
| Induction/Maintenance Chemotherapy | 0.62 | 0.35 | 0.23 |
Objective Response Rate (Complete + Partial Responses)
Response and progression in cases of SLL were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of CLL were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow. Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count. Progressive disease defined as 50% or more increase in the combined measurements of at least 2 lymph nodes as measured on CT scans or the appearance of new enlarged lymph nodes; 50% of more increase in the size of the spleen or liver; 50% or more increase in blood lymphocyte count. (NCT00974233)
Timeframe: 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up)
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | 7 |
| Partial Response (PR) | 12 |
| Stable Disease | 9 |
| Overall Response Rate | 19 |
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Lenalidomide and Sunitinib
Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participants health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 4.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death (NCT00975806)
Timeframe: First day of study drug to within 28 days after the last dose of the last study drug; The duration of exposure to lenalidomide and sunitinib was 7.0 to 327 and 7.0 to 328 days respectively
| Intervention | participants (Number) |
|---|
| Participants with at least 1 TEAE | Participants with at least 1 serious TEAE | ≥ 1 TEAE leading to stopping lenalidomide | ≥ 1 TEAE leading to stopping sunitinib | ≥ 1 TEAE -> dose reduction/interrruption of Len | ≥ 1 TEAE dose reduction/interrruption of Sunitinib | Participants with ≥1 TEAE related to lenalidomide | Participants with ≥1 TEAE related to Sunitinib | ≥ 1 NCI CTC Gr 3 or higher TEAE | ≥ 1 NCI CTC Gr 3 or higher related to lenalidomide | ≥ 1 NCI CTC Gr 3 or higher related to Sunitinib | ≥ 1 serious TEAE related to lenalidomide | ≥ 1 serious TEAE related to sunitinib |
|---|
| Cohort A: Lenalidomide 10mg and Sunitinib 37.5 mg | 5 | 3 | 2 | 2 | 5 | 5 | 5 | 5 | 5 | 4 | 4 | 2 | 1 |
,| Cohort F: Lenalidomide 10mg and Sunitinib 37.5mg | 7 | 4 | 2 | 2 | 6 | 5 | 7 | 7 | 6 | 5 | 5 | 2 | 2 |
,| Cohort G: Lenalidomide 15mg and Sunitinib 37.5mg | 4 | 2 | 2 | 2 | 4 | 3 | 4 | 4 | 4 | 4 | 4 | 0 | 2 |
Phase 1 : Tumor Response Rate According to RECIST 1.1
"Tumor response was evaluated every 3 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response was evaluated using the Response Criteria Evaluation in Solid Tumors (RECIST 1.1) criteria:~Treatment response includes both complete response and partial response~Complete response-disappearance of all lesions~Partial response-30% decrease in the sum of diameters of target lesions from baseline~Stable disease-neither shrinkage nor increase of lesions~Progressive Disease-20% increase in the sum of diameters of target lesions from nadir" (NCT00975806)
Timeframe: Every 3 cycles; up to month 25
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease |
|---|
| Cohort A: Lenalidomide 10mg and Sunitinib 37.5 mg | 0 | 1 | 1 |
,| Cohort F: Lenalidomide 10mg and Sunitinib 37.5mg | 0 | 0 | 3 |
,| Cohort G: Lenalidomide 15mg and Sunitinib 37.5mg | 0 | 0 | 3 |
Phase 1: Maximum Tolerated Dose (MTD)
"The MTD of lenalidomide in combination with sunitinib was defined as the highest dose level at which no more than 1 out of 6 participants experienced a dose limiting toxicity (DLT). Dose limiting toxicities were:~• Inability to deliver Lenalidomide in Cycle 1 due to a drug-related toxicity resulting in:~Grade (GR) 3 or 4 non-hematological toxicity lasting for ≥ 14 days~Febrile neutropenia~Gr 4 neutropenia lasting for ≥ 7 days~Gr 4 thrombocytopenia The occurrence of one of the above drug-related toxicities resulting in a clinical and/or laboratory assessment being done within 7 days following the initial finding to examine the participants for resolution of the toxicity. Lack of resolution of the toxicities was considered a DLT.~If ≤ 7 doses of lenalidomide or Sunitinib were missed in Cycle 1 due to non-drug related event, the participant data was to be included in the evaluation of dose escalation." (NCT00975806)
Timeframe: Within 21 days of first dose of treatment
| Intervention | mg (Number) |
|---|
| Cohort F: Lenalidomide 10mg and Sunitinib 37.5mg | 10 |
Progression-Free Survival (PFS)
PFS was the time from randomization to disease progression, or death, whatever occurred first. Progression criteria was met by analysis of target and non-target lesions as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters while on study or the appearance of one or more new lesions; an increase of at least 5mm as a total sum. Lymph nodes identified as target lesions (≥ 15 mm diameter in short axis) will be followed and reported by changes in diameter of short axis; or the unequivocal progression of a non-target lesion defined as an increase in the overall disease burden based on the change in non-measurable disease that is comparable in scope to the increase required to declare PD for measurable disease; Two or more new bone lesions as detected by bone scan (NCT00988208)
Timeframe: From randomization until disease progression or death from any cause; up to the cut-off date of 13 Jan 2012; maximum time on study was approximately 26 months
| Intervention | Weeks (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 46 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 45 |
Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria
Objective response (OR) is defined as having complete response (CR) or partial response (PR) as best overall response based on RECIST Criteria 1.1 and defines a CR = Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to <10mm; PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions taking as a reference the smallest sum of diameters and an absolute increase of ≥5 mm; the appearance of ≥1 new lesions; Stable Disease (SD)= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size <10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones (NCT00988208)
Timeframe: From day 1 to data cut-off 13 January 2012; maximum time on study was approximately 26 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 24.3 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 22.1 |
Percentage of Participants Who Received Post-Study Therapies
Percentage of Participants Who Received Post-Study Therapies for advanced Prostate Cancer. (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection;up to 5 years; up to the date of the final data analysis date of 20 April 2017
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 70.8 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 69.0 |
Overall Survival (OS)
Overall survival (OS) was the time from the date of randomization to the date of death from any cause. If no death was reported for a participant before the cut-off date for OS analysis, OS was censored at the last date at which the participant was alive. The median OS was calculated based on Kaplan-Meier estimates and corresponding 95% confidence interval (CI) was calculated using the method provided by Brookmeyer and Crowley. (NCT00988208)
Timeframe: From randomization until death from any cause up to the cut-off date of 13 January 2012; up to approximately 26 months
| Intervention | weeks (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | NA |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 77 |
Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial
Second primary malignancies were monitored as events of interest and reported as serious adverse events throughout the course of the trial. (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days
| Intervention | percentage of participants (Number) |
|---|
| Invasive Secondary Primary Malignancies | Non-invasive Secondary Primary Malignancies |
|---|
| Docetaxel/Prednisone/Lenalidomide (DPL) | 1.7 | 1.0 |
,| Docetaxel/Prednisone/Placebo (DP) | 1.3 | 0.4 |
Number of Participants With Treatment Emergent Adverse Events (AEs)
A TEAE is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; (NCT00988208)
Timeframe: From the time from of first dose of study drug administration to 28 days after the last dose of study drug and up to the data cut off date of 13 January 2012; the maximum duration of study drug was 93 weeks for DP and 90.6 weeks for DPL
| Intervention | participants (Number) |
|---|
| Any TEAE | Any TEAE related to lenalidomide or placebo | Any TEAE related to docetaxel/prednisone | Any severity grade 3-4 TEAE | Any serious AE (SAE) | Any SAE related to lenalidomide or placebo | Any SAE related to docetaxel/prednisone | Any AE causing discontinuation of lenalidomide/PBO | Any AE causing withdrawal of docetaxel/prednisone | Any TEAE leading to death |
|---|
| Docetaxel/Prednisone/Lenalidomide (DPL) | 517 | 412 | 481 | 381 | 279 | 167 | 182 | 150 | 169 | 24 |
,| Docetaxel/Prednisone/Placebo (DP) | 512 | 379 | 475 | 303 | 171 | 62 | 86 | 82 | 127 | 16 |
Time to Onset of Secondary Primary Malignancies
Time of Onset of Secondary Primary Malignancies was considered an event of interest (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days
| Intervention | months (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 29.7 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 19.7 |
Change in Childhood Autism Rating Scale (CARS)Value From Baseline to 6 Weeks
Change in CARS value from baseline to 6 weeks. Total CARS scores range from a fifteen to 60, with a minimum score of thirty serving as the cutoff for a diagnosis of autism on the mild end of the autism spectrum. (NCT00996931)
Timeframe: Baseline and 6 weeks
| Intervention | mean change in units on scale (Mean) |
|---|
| Lenalidomide | -2.08 |
Change in TNF-alpha Levels
Change in CSF-TNF-α from baseline to 12 weeks. (NCT00996931)
Timeframe: Baseline and 12 weeks
| Intervention | mean % change (Mean) |
|---|
| Lenalidomide | 57 |
Overall Response Rate
A Simon's two-stage minmax design will be used. Includes complete remission (CR) and partial remission (PR). Complete Response Requires the absence of disease signs and symptoms, and normalization of Peripheral blood and bone marrow. Partial Response it at lease a 50% reduction in disease signs and symptoms and normalization of peripheral blood. (NCT01002755)
Timeframe: Up to 8 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide, Ofatumumab) | 24 |
Number of Participants With Tolerance of the Medication Combination
Incidence of grade 3 and 4 non-hematological toxicity in more than 50 percent of the participants. Will be monitored based on the Bayesian model (beta-binomial). (NCT01002755)
Timeframe: Up to 8 years
| Intervention | participants (Number) |
|---|
| Treatment (Lenalidomide, Ofatumumab) | 0 |
Progression Free Survival
The time from the start of therapy to death, disease progression, or the initiation of the next therapy. Disease progression is the loss of response or transformation to a more aggressive histology. (NCT01002755)
Timeframe: Up to 8 years
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide, Ofatumumab) | 16 |
Best Response
The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Complete Response (CR): Absence of lymphadenopathy, hepatomegaly or splenomegaly by physical examination and appropriate radiographic techniques (if abnormal pre-treatment), No constitutional symptoms, ANC >/= 1,500/ul, platelets> 100,000/ul, Hgb>11gm/dl (untransfused); Partial Response (PR): >50% decrease in peripheral blood lymphocyte count from the pre-treatment baseline value, reduction in lymphadenopathy, reduction in size of the liver and/or the spleen; Progressive Disease (PD): Characterized by at least one of the following: > 50% increase in the sum of the products of at least 2 lymph nodes on at least 2 consecutive exams at least 2 weeks apart. At least 1 node must be >/= to 2cm in size, Appearance of new palpable LN, > 50% increase in size of liver or spleen determined by measurement below the respective costal (NCT01011894)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Participants Receiving Lenalidomide | 20 | 3 | 3 |
Morphologic Leukemia-free State
Defined as < 5% blasts on the BM aspirate with spicules and a count of >200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease. (NCT01016600)
Timeframe: Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]
| Intervention | participants (Number) |
|---|
| Cohort 1 | 2 |
| Cohort 2 | 1 |
| Cohort 3 | 2 |
| Phase II | 2 |
Partial Remission Rate (PR)
Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission. (NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 2 |
| Cohort 2 | 0 |
| Cohort 3 | 2 |
| Phase II | 5 |
Phase I Only - Maximum Tolerated Dose (MTD) as Measured by Dose-limiting Toxicities (DLTs)
"The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle.~Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle.~Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy." (NCT01016600)
Timeframe: Completion of the phase I portion of study (approximately 1 year and 4 months)
| Intervention | dose-limiting toxicities (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 0 |
| Cohort 3 | 0 |
Phase II Only - Complete Remission Rate (CRm + CRi) in Participants With Untreated AML ≥60 Years of Age
"Morphologic complete remission (CRm): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment.~Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul." (NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Phase II | 22 |
Phase I Only - Maximum Tolerated Dose (MTD)
"The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle.~Hematologic DLT is as a persistent bone marrow aplasia with ≤ 10 % cellularity, which persists for > 60 days from the start of a chemotherapy cycle.~Non-hematologic DLT is defined as any Grade 3 or Grade 4 non-hematologic toxicity that occurs during the first cycle with the specific exceptions of nausea, vomiting, anorexia, weight loss, infections or electrolyte abnormalities attributable to any other cause. Grade 3 triglycerides will be considered a DLT only for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy." (NCT01016600)
Timeframe: Completion of the phase I portion of study (approximately 1 year and 4 months)
| Intervention | mg/m^2 (Number) |
|---|
| Phase I Cohort | 75 |
Relapse Free Survival (RFS)
This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. (NCT01016600)
Timeframe: Until death - median follow-up 4.6 months (full range (0.3-31.4 months))
| Intervention | months (Median) |
|---|
| Cohort 1 | 12.0 |
| Cohort 2 | 1.4 |
| Cohort 3 | 4.9 |
| Phase II | 12.2 |
Time to Progression (TTP)
Defined as the interval from the date of the first dose of study drug to the date of progressive disease. (NCT01016600)
Timeframe: Until progressive disease - median follow-up 4.6 months (full range (0.3-31.4 months))
| Intervention | months (Median) |
|---|
| Cohort 1 | 5.7 |
| Cohort 2 | 3.4 |
| Cohort 3 | 7.8 |
| Phase II | 3.7 |
Response Rate (CRm + CRc + CRi + PR)
"Response rate (CRm + CRc + CRi + PR)~CRm = morphologic complete remission~CRc = cytogenetic complete remission~CRi = morphologic complete remission with incomplete blood count recovery~PR = partial remission" (NCT01016600)
Timeframe: Median number of cycles completed [3 cycles (12 weeks) full range (1 (4 weeks)-17 (68 weeks))]
| Intervention | participants (Number) |
|---|
| CRm | CRc | CRi | PR |
|---|
| Cohort 1 | 1 | 1 | 1 | 2 |
,| Cohort 2 | 0 | 0 | 1 | 0 |
,| Cohort 3 | 1 | 0 | 1 | 2 |
,| Phase II | 1 | 0 | 1 | 5 |
Toxicity Profile (Grade 3/4 Toxicities)
AML ≥18 years or untreated AML ≥60 years (NCT01016600)
Timeframe: 30 days after completion of treatment (median follow-up was 12 weeks (range 8-72 weeks))
| Intervention | participants (Number) |
|---|
| Anemia | Febrile neutropenia | Otitis mastoditis - worsening | Diarrhea | Nausea | Vomiting | Dental carries | Fatigue | Sepsis | Bronchial infection | Bacteremia | Lung infection | Skin infection | Activated partial thromboplastin time prolonged | Blood bilirubin increased | Creatinine increased | Neutrophil count decreased | Platelet count decreased | White blood cell count decreased | Lymphocyte count decreased | Dehydration | Hypernatremia | Hypocalcemia | Hypophosphatemia | Back pain | Generalized muscle weakness | Pain in extremity | Leukemia vasculitis left calf | Acute kidney injury | Dyspnea | Epistaxis | Productive cough | Pulmonary edema | Rash maculo-papular | Skin ulceration | Hypotension | Constipation | Edema limbs | Catheter related infection | Alanine aminotransferase increased | INR increased | Hyperglycemia | Hematuria | Cough | Wheezing | Cardiac arrest | Perianal hemorrhage | Cyst infection | Incarcerated hernia | Hypoalbuminemia | Hypokalemia | Respiratory failure | Pruritus | Hypertension | Atrial fibrillation | Chest pain cardiac | Left ventricular systolic dysfunction | Supraventricular tachycardia | Dysphagia | Esophagitis | Lower gastrointestinal hemorrhage | Pain | Otitis media | Scrotal infection | Upper respiratory infection | Urinary tract infection | Wound infection | Fall | Fracture | Weight loss | Anorexia | Hyponatremia | Neck pain | Polyarthropathy | Syncope | Pleuritic pain |
|---|
| Cohort 1 | 3 | 4 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 2 | 3 | 1 | 1 | 2 | 1 | 7 | 4 | 7 | 5 | 2 | 1 | 1 | 4 | 1 | 2 | 1 | 1 | 1 | 3 | 1 | 1 | 1 | 1 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 3 | 0 | 3 | 0 | 2 | 0 | 0 | 0 | 4 | 2 | 0 | 1 | 2 | 2 | 0 | 2 | 1 | 2 | 3 | 4 | 1 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Phase II | 4 | 8 | 0 | 0 | 1 | 2 | 0 | 4 | 1 | 0 | 0 | 9 | 2 | 0 | 3 | 0 | 2 | 6 | 10 | 2 | 3 | 0 | 0 | 6 | 0 | 2 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 5 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 1 | 2 | 2 |
Overall Survival
Defined as the date of first dose of study drug to the date of death from any cause. (NCT01016600)
Timeframe: Until death - median follow-up 4.6 months (full range (0.3-31.4 months))
| Intervention | months (Median) |
|---|
| Cohort 1 | 4.2 |
| Cohort 2 | 4.5 |
| Cohort 3 | 8.9 |
| Phase II | 4.3 |
CR With Incomplete Blood Counts Rate
Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. (NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 1 |
| Cohort 3 | 1 |
| Phase II | 1 |
Cytogenetic CR (CRc) Rate
Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). (NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 0 |
| Cohort 3 | 0 |
| Phase II | 0 |
Duration of CR for Complete Responders
(NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | months (Median) |
|---|
| Cohort 1 | 10.9 |
| Cohort 2 | 1.4 |
| Cohort 3 | 4.95 |
| Phase II | 12.15 |
Event Free Survival
Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. (NCT01016600)
Timeframe: Until death - median follow-up 4.6 months (full range (0.3-31.4 months))
| Intervention | months (Median) |
|---|
| Cohort 1 | 3.8 |
| Cohort 2 | 3.4 |
| Cohort 3 | 7.8 |
| Phase II | 2.9 |
Morphologic Complete Remission Rate (CRm)
Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. (NCT01016600)
Timeframe: Completion of treatment (median follow-up was 8 weeks) (range 4-68 weeks)
| Intervention | participants (Number) |
|---|
| Cohort 1 | 1 |
| Cohort 2 | 0 |
| Cohort 3 | 1 |
| Phase II | 1 |
Participants With Treatment Emergent Adverse Events (TEAEs)
"Participants with treatment-emergent adverse events (TEAEs) during the treatment period plus 30 days. A participant with multiple occurrences of an adverse event within a category is counted only once in that category. Adverse events were evaluated by the investigator.~The National Cancer Institute (NCI)'s Common Toxicity Criteria for AEs (NCI CTC) was used to grade AE severity. Severity grade 3= severe and undesirable AE. Severity grade 4= life-threatening or disabling AE." (NCT01021423)
Timeframe: up to 9 months
| Intervention | participants (Number) |
|---|
| At least one TEAE | At least one TEAE related to study drug | At least one NCI CTC grade 3-4 TEAE | At least one NCI CTC grade 3-4 related to drug | At least one serious TEAE | At least one serious TEAE related to drug | TEAE leading to discontinuation of drug | Related TEAE leading to discontinuation of drug | TEAE leading to dose reduction or interruption | Related TEAE - dose reduction or interruption |
|---|
| Lenalidomide | 4 | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
,| Placebo | 4 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
The Maximum Tolerated Dose (MTD) of Carfilzomib
Determine the MTD of Carfilzomib when combined with Lenalidomide and Dexamethasone. The estimated time to determine the MTD is 6 months. (NCT01029054)
Timeframe: 6 Months
| Intervention | mg/m^2 (Number) |
|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | 36 |
The Percentage of Patients Alive Without Progression
"The Progression Free Survival (PFS) rate will be determined at 12 and 24 months post treatment.~Progressive Disease (PD) is defined as an increase of greater than or equal to 25% from lowest response level in serum M-component and/ or urine M-component and/ or the difference between involved or uninvolved SFLC levels and/ or bone marrow % plasma cells. PD may also be the development of new bone lesions or soft tissue plasmacytomas or the increase in size of existing lesions. PD may also be the development of hypercalcemia." (NCT01029054)
Timeframe: 12 Months and 24 Months Post Treatment
| Intervention | percentage of patients (Number) |
|---|
| Percentage of Patients Without Progression at 12 m | Percentage of Patients Without Progression at 24 m |
|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | 97 | 92 |
The Percentage of Patients That Achieve a Response to Treatment
"The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined.~sCR is defined as:~Negative immunofixation on the serum and urine and~Disappearance of any soft tissue plasmacytomas and~< 5% plasma cells in bone marrow and~Normal SFLC ratio and~Absence of clonal cells in bone marrow~VGPR is defined as:~Serum and urine M-protein detectable by immunofixation but not on electrophoresis or~≥ 90% reduction in serum M-component with urine M-component < 100 mg per 24 hours~PR is defined as:~≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours~If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required" (NCT01029054)
Timeframe: 4 Months After Treatment Start
| Intervention | percentage of patients (Number) |
|---|
| % of patients that achieve at least a sCR | % of patients that achieve at least a VGPR | % of patients that achieve at least a PR |
|---|
| Carfilzomib, Lenalidomide w/Dexamethasone | 42 | 81 | 98 |
Mean Change From Baseline in the Emotional Functioning Domain Associated With the EORTC QLQ-C30 Scale at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -1.876 | -1.129 |
,| Placebo | 1.458 | -6.746 |
Healthcare Resource Utilization (HRU): Duration of Hospitalizations Due to Adverse Events
Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | Days (Median) |
|---|
| Placebo | 9.0 |
| Lenalidomide | 11.0 |
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Emotional Functioning Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | percentage of participants (Number) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 20.5 | 21.7 |
,| Placebo | 25.0 | 17.0 |
Number of Participants With Treatment Emergent Adverse Events (TEAE)
"A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.~A serious adverse event (SAE) is any:~Death;~Life-threatening event;~Any inpatient hospitalization or prolongation of existing hospitalization;~Persistent or significant disability or incapacity;~Congenital anomaly or birth defect;~Any other important medical event~The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 3.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death." (NCT01029262)
Timeframe: From the first dose of study drug through 28 days after discontinuation from the study treatment; up to the final data cut-off date of 03 July 2018; maximum exposure was 2100 days in the lenalidomide arm and 529 days in the placebo arm.
| Intervention | Participants (Count of Participants) |
|---|
| At least 1 TEAE | ≥ 1 Treatment Related AE (TEAE) | ≥ 1 Treatment related TEAE Causing Discontinuation | ≥ 1 TEAE Leading to Dose Reduction | ≥ 1 TEAE Leading to Dose Interruption | ≥ 1 TEAE Leading to Dose Interruption & Reduction | ≥ 1 TEAE Leading to Discontinuation of Study Drug | ≥ 1 Serious TEAE | ≥1 Treatment-Related Serious TEAE | ≥1 Serious TEAE Leading to Dose Reduction | ≥1 serious TEAE leading to dose interruption | ≥1 SAE Causing Dose Interruption & reduction | ≥1 Serious TEAE Leading to Stopping of Study Drug | ≥1 Grade (GR) 3-4 TEAE | ≥ 1 GR 3-4 Related TEAE | ≥ 1 GR 3-4 Leading to Dose Reduction | ≥ 1 GR 3-4 TEAE Leading to Dose Interruption | ≥ 1 GR 3-4 TEAE dose Interruption &reduction | ≥ 1 GR 3-4 TEAE Leading to Stopping of Study Med | ≥ 1 GR 5 TEAE | ≥1 GR Treatment Related 5 TEAE |
|---|
| Lenalidomide | 160 | 144 | 40 | 10 | 89 | 68 | 51 | 62 | 25 | 1 | 21 | 3 | 24 | 139 | 127 | 8 | 80 | 64 | 41 | 6 | 3 |
,| Placebo | 74 | 42 | 3 | 1 | 11 | 5 | 9 | 16 | 3 | 0 | 4 | 1 | 4 | 35 | 16 | 1 | 9 | 4 | 6 | 2 | 1 |
Mean Change From Baseline in the Physical Functioning Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Physical Functioning was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -2.919 | -1.484 |
,| Placebo | 0.732 | -5.451 |
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline Within the Physical Functioning Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | percentage of participants (Number) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 16.4 | 24.1 |
,| Placebo | 26.8 | 12.8 |
Percentage of Participants Who Achieved an Erythroid Response Based on the Modified International Working Group (IWG) 2006 Criteria
"A participant was considered as having achieved an erythroid response if the participant either:~- had a hemoglobin (Hgb) increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that also increased ≥1.5 g/dL. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe could be less <1.5 g/dL) OR - had a 50% reduction in the number of the RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden.~The baseline transfusion burden is the number of units over 112 days by the randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9 g/dL or less were used in this response assessment." (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 30.4 |
| Lenalidomide | 38.8 |
Mean Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -2.1 | -0.4 |
,| Placebo | -1.4 | -5.7 |
Mean Change From Baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life (QOL) Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -1.4 | -2.4 |
,| Placebo | -2.1 | -4.1 |
Mean Change From Baseline in the EORTC QLQ-C30 Fatigue Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). (NCT01029262)
Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 2.4 | -1.5 |
,| Placebo | 0.6 | 7.6 |
Mean Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Domain was scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -1.4 | 0.8 |
,| Placebo | 1.2 | -7.1 |
Mean Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain at Week 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). (NCT01029262)
Timeframe: Baseline and Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 2.2 | 1.2 |
,| Placebo | 0.6 | 4.3 |
Mean Change From Baseline in the Global Health Status/QoL Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | -2.690 | -2.441 |
,| Placebo | -1.201 | -4.502 |
Mean Change From Baseline in the Dyspnea Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 3.374 | -0.206 |
,| Placebo | 1.696 | 5.998 |
Mean Change From Baseline in Fatigue Domain Associated With the EORTC QLQ-C-30 Scale at Week 12 and Week 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 3.497 | 0.196 |
,| Placebo | -0.464 | 7.376 |
Compliance Rates Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) From Baseline to Week 48
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A participant was considered compliant at a visit if at least 15 out of the QLQ-C30 items in the questionnaire were checked. (NCT01029262)
Timeframe: Baseline, Week 12, (±3 days), Week 24, (±3 days), Week 36, (±3 days), and Week 48 (±3 days); up to data cut-off of 17 Mar 2014
| Intervention | percentage of participants (Number) |
|---|
| Baseline | Week 12 | Week 24 | Week 36 | Week 48 |
|---|
| Lenalidomide | 90 | 83.8 | 85.8 | 80.5 | 71.9 |
,| Placebo | 88.6 | 78.5 | 80.6 | 100 | 50 |
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Dyspnea Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom). Improvement means at least 10 points better compared to baseline. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | percentage of participants (Number) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 21.3 | 20.5 |
,| Placebo | 19.6 | 12.8 |
Percentage of Participants Who Achieved an Erythroid Response Based on Original IWG 2006 Criteria
"A participant was considered as having achieved an erythroid response when:~- a Hgb increase ≥1.5 g/dL compared to baseline and confirmed by another central laboratory hemoglobin value at 4 to 8 weeks after the first Hgb measurement that had also increased ≥1.5 g/dL for at least 8 weeks. All Hgb values during this time interval must have had a ≥ 1.5 g/dL increase (ie, no central laboratory Hgb increase during this timeframe can be less than a 1.5 g/dL) OR - had an absolute reduction of 4 RBC transfusion units over any consecutive 56 days period compared to the baseline transfusion burden.~The baseline transfusion burden is the number of units over the 112 days prior to randomization divided by 2. Only transfusions given for a pre-transfusion Hgb value of 9.5 g/dL or less may be used in this response assessment." (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 20.3 |
| Lenalidomide | 35.6 |
Percentage of Participants With a Erythroid Gene Signature Who Achieved RBC Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
"The percentage of participants who achieved the 56-day RBC TI response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). A participant who achieved at least a 56-day RBC-transfusion-independent response was considered a 56-day RBC-TI responder." (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 0.0 |
| Lenalidomide | 7.1 |
Percentage of Participants With a Clinically Meaningful Improvement in HRQOL Associated With the EORTC QLQ-C-30 Scale From Baseline in the Global Health Status/QOL Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered clinically meaningful. (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | percentage of participants (Number) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 22.1 | 26.5 |
,| Placebo | 19.6 | 14.9 |
Percentage of Participants With a Clinically Meaningful Improvement in QOL (EORTC QLQ-C-30 Scale) From Baseline in Fatigue Domain at Weeks 12 and 24
The European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) was a 30-item oncology-specific questionnaire. The questionnaire was developed to assess the quality of life of cancer patients. It contains 30 questions, 24 of which form 9 multi-item scales representing various aspects of HRQOL: 1 global scale, 5 functional scales (Physical, Role, Emotional, Cognitive and Social), and 3 symptom scales (Fatigue, Pain, and Nausea). The remaining 6 items are intended to be mono-item scales describing relevant cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, financial difficulties). Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Improvement means at least 10 points better compared to baseline (NCT01029262)
Timeframe: Baseline, Week 12, ±3 days and Week 24, ±3 days
| Intervention | percentage of participants (Number) |
|---|
| Week 12 | Week 24 |
|---|
| Lenalidomide | 39.3 | 38.6 |
,| Placebo | 30.4 | 29.8 |
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days as Determined by an Independent Review Committee (IRC)
"The percentage of participants who achieved the 56-day RBC transfusion independent (TI) response was defined as the absence of any RBC transfusions during any consecutive rolling 56-day interval within the double-blind treatment phase (ie, Days 2 (Day 1 is the first study drug day) to 57, Days 3 to 58, etcetera). The double-blind treatment phase was defined as the period between the 1st dosing up until 28 days after the last study drug dose" (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 2.5 |
| Lenalidomide | 26.9 |
Kaplan Meier Estimates for Progression to Acute Myeloid Leukemia (AML)
Progression to AML is part of the natural course of MDS and is a manifestation of disease progression. The time to progress to AML was calculated from the day of randomization to the first day when AML was diagnosed. Participants who died without AML were censored at the date of death. The participants who were lost to follow-up were censored at the last known day when participants did not have AML. Participants who did not progress to AML at the last follow-up contact were censored at the day of the last follow-up contact. (NCT01029262)
Timeframe: From randomization to final data cut-off date of 03 Jul 2018; median follow up time for progression to AML was 2.3 years (range = 0 to 5.0 years) in the placebo arm and 2.6 years (range = 0 to 6.4 years) in the lenalidomide arm.
| Intervention | years (Median) |
|---|
| Placebo | NA |
| Lenalidomide | NA |
Kaplan Meier Estimate for Overall Survival (OS)
Overall survival was assessed using the time between randomization and the date of death or date of censoring. Participants who were alive at a data cutoff date and participants who were lost to follow-up were censored at the last date when participants were known to be alive. (NCT01029262)
Timeframe: From randomization to final data cut-off date of 03 July 2018; maximum survival follow up was 6.4 years
| Intervention | years (Median) |
|---|
| Placebo | 3.0 |
| Lenalidomide | 3.8 |
Healthcare Resource Utilization (HRU): Number of Days of Hospitalization Due to Adverse Events Per Person-Years
Hospitalizations due to adverse events exclude those for transfusions, elective procedures or protocol-driven procedures. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient (NCT01029262)
Timeframe: From first dose of study drug until 28 days after the last dose, as of the data cut-off date of 17 March 2014; median (minimum, maximum) duration of treatment was 168 (14, 449) and 164 (7, 1158) days in each treatment group respectively.
| Intervention | Days per person-years (Number) |
|---|
| Placebo | 6.37 |
| Lenalidomide | 8.92 |
Best Overall Response Assessed by an Independent Review Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) During the Proof of Concept Period Prior to Early Study Termination
"Tumor response was evaluated every 2 cycles beginning with Cycle 3 Day 1 and at treatment discontinuation. Response and progression were evaluated using the RECIST 1.1 criteria (Eisenhauer, 2009).~Complete response-disappearance of all lesions~Partial response-30% decrease in the sum of diameters of target lesions from baseline~Stable disease-neither shrinkage nor increase of lesions.~Progressive Disease-20% increase in the sum of diameters of target lesions from nadir.~Participants with evidence of objective tumor response have the response confirmed with repeat assessments performed at the next scheduled scan." (NCT01032291)
Timeframe: Week 9 up to week 24
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Response Not Evaluable |
|---|
| Lenalidomide (Proof of Concept) | 0 | 0 | 3 | 13 | 5 |
,| Lenalidomide Plus Cetuximab (Proof of Concept) | 0 | 0 | 5 | 13 | 3 |
Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle of the Safety Lead-In Period
"The number of participants with DLTs determines the maximum tolerated dose of the combination therapy used in the Proof of Concept (POC) period:~If <2 of the initial 6 participants experience a DLT, then the POC will start with lenalidomide at 25 mg.~If ≥2 of the initial 6 participants experienced a DLT, then 6 more subjects were to be enrolled at 20 mg lenalidomide.~If <2 of the additional 6 subjects experienced a DLT, then the lenalidomide starting dose for the POC was to be 20 mg.~If ≥2 of the additional 6 subjects experienced a DLT, then 6 more subjects were to be enrolled at 15 mg lenalidomide.~If <2 of the additional 6 subjects experienced a DLT, then the POC was to start with lenalidomide at 15 mg.~If ≥2 of the additional 6 subjects experienced a DLT, the dosing for the study was to be reassessed by Celgene Corporation and the investigators." (NCT01032291)
Timeframe: Up to Day 28 (Cycle 1)
| Intervention | participants (Number) |
|---|
| Lenalidomide Plus Cetuximab (Safety Lead-in) | 1 |
Participants With Treatment-Emergent Adverse Events (TEAE)
TEAEs are any adverse event occurring or worsening on or after the first treatment of any study drug and within 28 days after the last dose of the last study drug received. Relation to study drug was determined by the investigator. Severity of AE is graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.0. Severity is a 5-point scale: 3= severe or medically significant but not life-threatening 4=life-threatening, urgent intervention required 5=death related to AE. (NCT01032291)
Timeframe: up to week 28
| Intervention | participants (Number) |
|---|
| >=1 TEAE | Serious TEAE | TEAE leading to discontinuing lenalidomide | TEAE leading to discontinuing cetuximab | TEAE leading to reduction/interruption of lenalido | TEAE leading to reduction/interruption of cetuxima | TEAE related to lenalidomide | TEAE related to cetuximab | TEAE NCI CTC grade 3 or higher | TEAE NCI CTC grade 3+ related to lenalidomide | TEAE NCI CTC grade 3+ related to cetuximab | Serious TEAE related to lenalidomide | Serious TEAE related to cetuximab |
|---|
| Lenalidomide (Proof of Concept) | 20 | 9 | 7 | NA | 6 | NA | 9 | NA | 13 | 4 | NA | 0 | NA |
,| Lenalidomide Plus Cetuximab (Proof of Concept) | 21 | 9 | 5 | 6 | 9 | 7 | 13 | 19 | 12 | 4 | 7 | 2 | 2 |
,| Lenalidomide Plus Cetuximab (Safety Lead-In) | 8 | 5 | 3 | 3 | 2 | 1 | 5 | 8 | 4 | 3 | 2 | 2 | 2 |
Duration of Response
The response duration was measured from the last of the consecutive 56 days during which the subject was free of red blood cells (RBC) transfusions to the date of the first RBC transfusion after the 56-day RBC-transfusion-free period. (NCT01034592)
Timeframe: 6 months
| Intervention | days (Median) |
|---|
| Lenalidomide | 0 |
Hemoglobin Concentration
The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL. (NCT01034592)
Timeframe: 6 months
| Intervention | g/dL (Median) |
|---|
| Lenalidomide | 0.4 |
Red Blood Cell (RBC) Transfusion Independence
"Red blood cell (RBC) transfusion independence is reported as the number of subjects who achieve a continuous absence of the intravenous infusion of any RBC transfusion during any consecutive rolling 56 days during the treatment period." (NCT01034592)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Lenalidomide | 0 |
Platelet Response
The effect on platelet levels as assessed as the change in platelet count from baseline. (NCT01034592)
Timeframe: 6 months
| Intervention | 1000/uL (Median) |
|---|
| Lenalidomide | 25.5 |
Toxicity
Toxicity was assessed as the number of adverse events related to lenalidomide. (NCT01034592)
Timeframe: 6 months
| Intervention | Related Adverse Events (Number) |
|---|
| Lenalidomide | 1 |
Red Blood Cell (RBC) Transfusions
The effect on red blood cell (RBC) transfusions was assessed as the number of participants that achieved a greater than 50% decrease in RBC transfusion requirements. (NCT01034592)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide | 0 |
Neutrophil Response
The effect on neutrophil levels was assessed as the change in neutrophil count from baseline. (NCT01034592)
Timeframe: 6 months
| Intervention | 1000/uL (Median) |
|---|
| Lenalidomide | 0.50 |
Overall Survival
The Kaplan-Meier method will be used to estimate the overall survival distribution. This outcome only reports data as it pertains to overall survival at one year. All-cause mortality includes survival for follow up for all subjects on the study. (NCT01035463)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| All Phase I Participants | 100 |
| All Phase II Participants | 95 |
Maximum Tolerated Dose of Lenalidomide (Phase I)
The Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 3 out of 6 subjects experience dose limiting toxicities during cycle 1. Dose limiting toxicities graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCT01035463)
Timeframe: Cycle 1, 28 days
| Intervention | milligrams PO daily (Number) |
|---|
| Treatment (Stem Cell Transplantation) | 10 |
Event-free Survival
The Kaplan-Meier method will be used to estimate the event-free survival distribution. (NCT01035463)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| All Phase I Participants | 84 |
| All Phase II Participants | 87 |
Overall Response: Number of Participants With CR or CRi Response
Response defined as complete remission (CR) or complete remission with incomplete platelet recovery (CRi) for AML or any response for myelodysplastic syndrome (MDS) using international working group (IWG)-06 criteria. Complete response (CR) requires normalization of peripheral counts (absolute neutrophil count 10^9/L or more, platelet count 100 x 10^9/L or more), and a bone marrow with 5% or less marrow blasts. A hematologic improvement (HI) is defined as a CR with a platelet count above 30 x 10^9/L, without the need for transfusion of Platelets. (NCT01038635)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Complete Remission (CR) | Incomplete Count Recover (CRi) |
|---|
| Overall Study: 5-AZA + LEN MTD | 15 | 16 |
Overall Response Rate (ORR) of Lenalidomide in Combination With 5-azacytidine (5-AZA) in Participants With Leukemia
Response defined as complete remission (CR) or complete remission with incomplete platelet recovery (CRi) for AML or any response for myelodysplastic syndrome (MDS) using international working group (IWG)-06 criteria. Complete response (CR) requires normalization of peripheral counts (absolute neutrophil count 10^9/L or more, platelet count 100 x 10^9/L or more), and a bone marrow with 5% or less marrow blasts. A hematologic improvement (HI) is defined as a CR with a platelet count above 30 x 10^9/L, without the need for transfusion of Platelets. (NCT01038635)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Phase I: 5-AZA + LEN MTD | 14 |
| Phase II: 5-AZA + LEN | 45 |
Number of Dose Limiting Toxicities for Determining Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With 5-azacytidine (5-AZA)
DLT determined only during first course of therapy, at least 28 days from treatment of last participant before a new dose level initiated. All severe (Grade 3-4) non-hematological toxicities that are drug related considered for DLT determination. If 1 participant develops grade III-IV non-hematological toxicity, 3 more will be accrued at that particular dose level. If 2 or more participants develop grade III-IV non-hematologic toxicity, the doses of the combination at which this occurs will be considered too toxic. A total of 10 patients will be treated at the maximally tolerated dose (MTD) of the combination (the dose level below that considered to be too toxic) to confirm its tolerability. (NCT01038635)
Timeframe: 3-8 week cycles, up to 24 weeks
| Intervention | participants (Number) |
|---|
| 5-AZA + 5 Days LEN 10 mg | 0 |
| 5-AZA + 5 Days LEN 15 mg | 0 |
| 5-AZA + 5 Days LEN 20 mg | 0 |
| 5-AZA + 5 Days LEN 25 mg | 0 |
| 5-AZA + 5 Days LEN 50 mg | 0 |
| 5-AZA + 5 Days LEN 75 mg | 0 |
| 5-AZA + 10 Days LEN 75 mg 75 mg | 0 |
Progression Free Survival (Phase II)
The progression-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone or death due to any cause, whichever comes first. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria. (NCT01049945)
Timeframe: Up to 2 years from study completion
| Intervention | months (Median) |
|---|
| Maximum Tolerated Dose, Dose Level 4 | 11.8 |
Overall Survival (Phase II)
The overall survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. The overall survival rate at 6 months is defined as the percentage of participants who are alive at 6 months. (NCT01049945)
Timeframe: at 6 months
| Intervention | percentage of participants (Number) |
|---|
| Maximum Tolerated Dose, Dose Level 4 | 87 |
Event Free Survival (Phase II)
The event-free survival time is defined as the time from registration to disease progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma. The distribution of event-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria. (NCT01049945)
Timeframe: Up to 2 years from study completion
| Intervention | months (Median) |
|---|
| Maximum Tolerated Dose, Dose Level 4 | 5.6 |
Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)
"The Maximum Tolerated Dose (MTD) is the dose level below that at which a dose limiting toxicity (DLT) is observed in ≥ 33% (i.e., ≥ 2 of 6) subjects in a cohort. A dose limiting toxicity is defined as one of the following adverse events in the Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 deemed at least possibly related to treatment:~Grade 2 neuropathy with pain~Any grade 3 Non-Hematologic toxicity~Any grade Non-Hematologic event requiring a dose reduction in cycle 1 or delaying the next cycle by >14 days.~Grade 4 neutropenia~Febrile neutropenia~Grade 4 thrombocytopenia~Grade 3 thrombocytopenia associated with bleeding~Any Hematologic event requiring a dose reduction in cycle 1 or a delay in the next cycle of treatment by >14 days.~We are reporting the results of this endpoint as the number of DLTs per dose level." (NCT01049945)
Timeframe: One cycle of treatment
| Intervention | Dose Limiting Toxic Events (Number) |
|---|
| Phase I, Dose Level 1 | 0 |
| Phase I, Dose Level 2 | 1 |
| Phase I, Dose Level 3 | 0 |
| Phase I, Dose Level 4 | 0 |
| Phase I, Dose Level 5 | 2 |
Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR).
"Complete response (CR)~- Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.~Stringent complete response (sCR) - A CR plus normal FLC ratio and no clonal cells in bone marrow~Near complete response (nCR) A CR, with the persistence of original monoclonal protein~Very good partial response (VGPR)~- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h~Partial response (PR)~≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.~a ≥50% decrease in the difference between involved and uninvolved FLC levels~or a ≥50% reduction in plasma cells is required in place of M-protein, if ≥30% at baseline." (NCT01049945)
Timeframe: Up to 6 cycles of treatment
| Intervention | percentage of participants (Number) |
|---|
| Maximum Tolerated Dose, Dose Level 4 | 44 |
Duration of Response (DOR) (Phase II)
DOR is the time from the date the patient's objective status is first noted to be PR or better to the earliest date of progression (PD=Increase of > 25% from lowest response value in Serum/Urine M-component) is documented. Treatment response was assessed using the International Myeloma Working Group uniform criteria. Complete response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Stringent complete response (sCR)=A CR plus normal FLC ratio and no clonal cells in bone marrow. Near complete response (nCR)=A CR, with the persistence of original monoclonal protein. Very good partial response (VGPR) =Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h, Partial response (PR)=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h. (NCT01049945)
Timeframe: Up to 2 years from study completion
| Intervention | months (Median) |
|---|
| Maximum Tolerated Dose, Dose Level 4 | 24.4 |
Complete Response Rate at 6 Months
16 of 17 patients proceeded to transplant. 6 month CR rate post transplant was 8/16 (50%). (NCT01050790)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 50 |
Time to Progression Post Transplant
Time to progression post transplant: For patients not in Complete Response (CR), progressive disease requires one or more: >25% increase in the level of the serum monoclonal paraprotein(absolute increase of at least 0.5 g/dL); > 25% increase in 24-hour urinary light chain excretion(absolute increase of at least 200m/24 hours). Increase plasma cells in a bone marrow aspirate( absolute increase of at least 10%). Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum Ca > 11.5 mg/dL or > 2.65 mmol/L) not attributable to any other cause. All relapse categories require two consecutive assessments made any time before classification as relapse or progressive disease. (NCT01050790)
Timeframe: 28 months
| Intervention | months (Median) |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 14.9 |
CTA Expression Before and After Azacitidine Therapy
Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. (NCT01050790)
Timeframe: 3 months
| Intervention | participants (Number) |
|---|
| CTA up-regulation | CD138+ cells | unfractionated bone marrow | CTA (CTAG1B)-specific T cell response |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 6 | 2 | 4 | 3 |
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment
Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment. (NCT01050790)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| mobilize lymphocytes | lymphocytes infused post transplant | not able to mobilize stem cells/no transplant |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 17 | 16 | 1 |
Progression-free and Overall Survival
"Survival and event-free survival curves (any event of fatality, relapse, acute or chronic GVHD) with Kaplan-Meier curves. The incidence curve for relapse - accounting for the competing risk of fatality - is plotted with step-wise curves. The R statistical software (version 2.15) was used for all time-to-event analyses, with the survival package used for survival curves, and the cmprsk package used for all competing risk curves.~Results: The one-year survival rate is 93.3% (SE = 0.4%), and the two-year survival rate is 86.1% (SE = 0.9%)." (NCT01050790)
Timeframe: 1 year to 2 years
| Intervention | percentage of participants (Number) |
|---|
| one- year survival rate | two-year survival rate | one-year relapse rate | two-year relapse rate | one-year event free survival rate | two-year event free survival rate |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 93.3 | 86.1 | 12.5 | 19.2 | 87.5 | 67.3 |
Toxicity as Assessed by NCI CTCAE v3.0
Time frame includes after stem cell transplant engraftment. Toxicity post ALI infusion: 1 patient grade 1 hypertension 90 min post infusion. Toxicity post Rev maintenance: 1 patient not tolerated, 1 patient dose decreased due to counts. (NCT01050790)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Toxicity post ALI infusion | Toxicity post Rev maintenance |
|---|
| 5-azacytidine + Lenalidomide -> Auto Stem Cell Transplant | 1 | 2 |
Number of Participants With 1 Year Overall Survival (OS)
The 1 year overall survival of older adults with mildly symptomatic multiple myeloma treated on this response adapted approach (NCT01054144)
Timeframe: 1 Year
| Intervention | participants (Number) |
|---|
| Response Adapted Therapy | 27 |
Number of Participants With Serious Adverse Events
Number of participants with serious adverse events (NCT01054144)
Timeframe: Day 1 through Off Study Date, an average of 48 months
| Intervention | participants (Number) |
|---|
| Response Adapted Therapy | 20 |
Response Rate
Response rate in older adults with mildly symptomatic multiple myeloma to single agent lenalidomide, lenalidomide prednisone and lenalidomide low dose dexamethasone in patients with suboptimal responses to lenalidomide monotherapy. The study used the uniform response assessment of the International Myeloma Working Group with the addition of MR (minimal response) (Durie et al, 2006; Kumar et al, 2016). MR was defined as a 25-49% decrease in serum M spike, and a 50-89% improvement in urine M spike. For patients without a measurable serum or urine M spike, a 25-49% decrease in the difference between the involved and uninvolved free light chains was required. The response in this trial is defined as complete remission (CR), stringent complete remission (SRC), very good partial remission (VGPR) and partial remission (PR) and minimal response (MR). (NCT01054144)
Timeframe: Every 8 weeks up to 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response & Stringent Complete Response | Very Good Partial Response (VGPR) | Partial Response (PR) | Minimal Response (MR) | Stable Disease | Overall Response >/= PR |
|---|
| Response Adapted Therapy | 1 | 1 | 2 | 5 | 0 | 4 |
,| Single Agent Lenalidomide | 4 | 3 | 12 | 4 | 3 | 19 |
Tumor Response Rate
"Percentage of patients who achieve a partial or complete response Complete response was defined as the absence of any detectable residual disease, including tumor-associated edema, that persisted for at least 4 weeks.~Partial response was defined as no new lesions (skin or oral), or new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions), and a 50% or greater decrease in the number of all previously existing lesions that lasted for at least 4 weeks, or complete flattening of at least 50% of all previously raised lesions, or a 50% or greater decrease in the sum of the products of the largest perpendicular diameters of the marker lesions." (NCT01057121)
Timeframe: Up to 30 days after completion of study treatment
| Intervention | percent of participants who responded (Number) |
|---|
| Phase I - 10 mg/Day (Lenalidomide) | 0 |
| Phase I - 15 mg/Day (Lenalidomide) | 0 |
| Phase I: 20 mg/Day Lenalidomide | 50 |
| Phase I: 25 mg/Day Lenalidomide | 80 |
| Phase II: 25 mg/Day Lenalidomide | 53 |
Maximum Tolerated Dose of Lenalidomide Defined as the Dose Level at Which 0/6 or 1/6 Subjects Experience Dose Limiting Toxicity (DLT) With the Next Higher Dose Having at Least 2/3 or 2/6 Subjects Encountering DLT (Phase I)
Maximum tolerated dose (MTD) of lenalidomide defined as the dose level at which 0/6 or 1/6 subjects experience dose limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 subjects encountering DLT (Phase I). Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Using a 3+3 design, the MTD is defined as the level at which 0/6 or 1/6 patients experiences at dose-limiting toxicity in the first cycle. (NCT01057121)
Timeframe: 28 days
| Intervention | mg per day of lenalidomide (Number) |
|---|
| Phase I - Treatment (Lenalidomide) | 25 |
Time to Death
Percentage of patients who died (NCT01057121)
Timeframe: Up to 30 days after completion of study treatment
| Intervention | percentage of participants who died (Number) |
|---|
| Phase I - 10 mg/Day Lenalidomide | 0 |
| Phase I - 15 mg/Day Lenalidomide | 0 |
| Phase I: 20 mg/Day Lenalidomide | 0 |
| Phase I: 25 mg/Day Lenalidomide | 0 |
| Phase II: 25 mg/Day Lenalidomide | 0 |
Time to Response
"time from enrollment to first response (complete or partial) as defined below: Complete response is defined as the absence of any detectable residual disease, including tumor-associated edema, persisting for at least 4 weeks.~Partial response is defined as no new lesions (skin or oral), or new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions), and a 50% or greater decrease in the number of all previously existing lesions lasting for at least 4 weeks, or complete flattening of at least 50% of all previously raised lesions, or a 50% or greater decrease in the sum of the products of the largest perpendicular diameters of the marker lesions." (NCT01057121)
Timeframe: Up to 30 days after completion of study treatment
| Intervention | weeks (Median) |
|---|
| Phase I: 20 mg/Day Treatment (Lenalidomide) | 8 |
| Phase I: 25 mg/Day Treatment (Lenalidomide) | 20.5 |
| Phase II: 25 m/Day Treatment (Lenalidomide) | 13 |
Phase I: Maximum Tolerated Dose (MTD) of Lenalidomide
The maximum tolerated dose (MTD) will be defined as the next lowest dose cohort below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1. (NCT01060384)
Timeframe: 7 months
| Intervention | milligrams (Number) |
|---|
| Phase 1 | 10 |
Phase I and Phase II: Event Free Survival and Overall Survival
"Event free survival is defined as the time from start of treatment to disease progression or death from any cause. Overall survival (OS) is defined as the time from start of treatment to death from any cause. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy.~A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A non-evaluable subject will be one who receives less than one complete cycle of therapy (ie. 4 infusions of ofatumumab and 21 days of lenalidomide). A non-evaluable subject will also be one that has no documented response prior to treatment withdrawal." (NCT01060384)
Timeframe: 2 years from start of treatment
| Intervention | percent of participants (Number) |
|---|
| Estimated 1 year Event Free Survival | Estimated 1 year Overall Survival | Estimated 2 year Event Free Survival | Estimated 2 year Overall Survival |
|---|
| Phase II: Lemalidomide at MTD and Ofatumumab | 38 | 53 | 20 | 44 |
Overall Survival for All Eligible Patients
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT01075321)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| All Patients (Everolimus and Lenalidomide) | 20.3 |
Progression-Free Survival For All Eligible Patients
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier. (NCT01075321)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| All Patients (Everolimus and Lenalidomide) | 5.3 |
Time to Treatment Failure for All Eligible Patients
Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier. (NCT01075321)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| All Patients (Everolimus and Lenalidomide) | 4.7 |
Number of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I)
The number of dose-limiting toxic events (DLT) for this combination of drug treatment will determine the Maximum Tolerated Dose (MTD) in subsequent phases of this study. The following events were defined as a DLT: a grade 4+ Neutropenia or platelet count decrease, a grade 4 infection, or any grade 3+ non-hematologic event as assessed using Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. Here, the number of patients reporting a DLT are reported (NCT01075321)
Timeframe: After one 28 day cycle
| Intervention | Participants (Count of Participants) |
|---|
| Phase I: Dose Level -1 | 1 |
| Phase I: Dose Level 0 | 2 |
| Phase I: Dose Level 1 | 3 |
| Phase II: Dose Level 0 | 0 |
Duration of Response for All Eligible Patients
Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest objective status is first noted to be either a CR or PR to the earliest date progression is documented. (NCT01075321)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| All Patients (Everolimus and Lenalidomide) | 14.7 |
Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only
Incidence of dose-limiting toxicity (DLT) defined as any grade 3 or 4 adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) (NCT01076543)
Timeframe: 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I, All Histologies, Lenalidomide 15 mg | 1 |
| Phase I, All Histologies, Lenalidomide 20 mg | 0 |
| Phase I, All Histologies, Lenalidomide 25 mg | 3 |
| Phase II, Diffuse Large B-Cell Subtype | 0 |
| Phase II, Follicular Subtype | 0 |
| Phase II, Lymphoma NOS | 0 |
Complete Response (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; (NCT01076543)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Phase I, All Histologies, Lenalidomide 15 mg | 0 |
| Phase I, All Histologies, Lenalidomide 20 mg | 0 |
| Phase I, All Histologies, Lenalidomide 25 mg | 0 |
| Phase II, Diffuse Large B-Cell Subtype | 5 |
| Phase II, Follicular Subtype | 5 |
| Phase II, Lymphoma NOS | 7 |
Overall Response Rate (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01076543)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Phase I, All Histologies, Lenalidomide 15 mg | 0 |
| Phase I, All Histologies, Lenalidomide 20 mg | 0 |
| Phase I, All Histologies, Lenalidomide 25 mg | 0 |
| Phase II, Diffuse Large B-Cell Subtype | 10 |
| Phase II, Follicular Subtype | 7 |
| Phase II, Lymphoma NOS | 25 |
Overall Survival (OS) (Phase II)
Kaplan-Meier curves will be generated for OS stratified by histology; median OS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley. (NCT01076543)
Timeframe: Time from study entry until death from any cause, assessed up to 6 years
| Intervention | Months (Median) |
|---|
| Phase II, Diffuse Large B-Cell Subtype | 9.1 |
| Phase II, Follicular Subtype | 35.8 |
| Phase II, Lymphoma NOS | 25.5 |
Progression-free Survival (PFS) (Phase II)
Kaplan-Meier curves will be generated for PFS stratified by histology; median PFS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley. (NCT01076543)
Timeframe: Time from study entry until disease progression or death from any cause, assessed up to 5 years
| Intervention | Months (Median) |
|---|
| Phase II, Diffuse Large B-Cell Subtype | 7.0 |
| Phase II, Follicular Subtype | 27.7 |
| Phase II, Lymphoma NOS | 7.0 |
Participants With Grade 3 =/> Adverse Events
Number of participants experiencing adverse events above a Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 2. (NCT01079936)
Timeframe: Day 90 after stem cell transplant
| Intervention | participants (Number) |
|---|
| 25 Mg Lenalidomide | 3 |
| 50 mg Lenalidomide | 5 |
| 75 mg Lenalidomide | 15 |
| 100 mg Lenalidomide | 17 |
Number of Participants With Response (CR at Day 90)
Response is defined as the event that the participant is alive with complete response (CR) at day 90 (+/-30 days). CR defined as: A) Absence of monoclonal protein in urine and serum when analyzed by immunofixation electrophoresis. B) The bone marrow should be normal by morphological examination with <5% plasma cells. There should be < 1% aneuploid light chain restricted population by flow cytometry for DNA/cIg. C) While healing of bone lesions not required, no new lytic lesion should appear. Further compression fracture of spine will be not considered as progressive disease. (NCT01079936)
Timeframe: Day 90 after stem cell transplant
| Intervention | participants (Number) |
|---|
| 25 Mg Lenalidomide | 0 |
| 50 mg Lenalidomide | 0 |
| 75 mg Lenalidomide | 4 |
| 100 mg Lenalidomide | 4 |
Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II)
Dose limiting toxicity (DLT) was defined as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. (NCT01079936)
Timeframe: Day 30 following transplant
| Intervention | participants (Number) |
|---|
| 25 Mg Lenalidomide | 0 |
| 50 mg Lenalidomide | 0 |
| 75 mg Lenalidomide | 2 |
| 100 mg Lenalidomide | 0 |
Maximum Tolerated Dose (MTD) of Lenalidomide
There were 4 doses of lenalidomide in the dose escalation phase: 25 mg, 50 mg, 75 mg, and 100 mg. The first 12 patients were treated at these dose levels (3 patients per level) and safety assessed at each level. The MTD dose level was to be the level at which participants at each lenalidomide dose level had no dose limiting toxicity (DLT). DLT defined as as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. Each participant received a fixed dose of Melphalan plus one of the four doses 25, 50, 75 or 100 mg of Lenalidomide orally for each of 7 days, -8 to -2 pre transplant. (NCT01079936)
Timeframe: Assessed at 21-28 Day Cycle
| Intervention | mg/day (Number) |
|---|
| Lenalidomide + High-Dose Melphalan | 100 |
Overall Response Rate
Overall response rate is defined as the percentage of participants who achieved either a confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as their best response based on the Independent Review Committee (IRC) assessed response outcome. Response was determined using the International Myeloma Working Group - Uniform Response Criteria (IMWG-URC). (NCT01080391)
Timeframe: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 66.7 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 87.1 |
Duration of Response
Duration of response (DOR) was calculated for participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). Duration of response was defined as the time in months from the initial start of response (PR or better) to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for PFS. (NCT01080391)
Timeframe: From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 42 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 21.2 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 28.6 |
Duration of Disease Control
Duration of disease control (DDC) was calculated for participants who achieved disease control. DDC was defined as the time in months from randomization to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for PFS. (NCT01080391)
Timeframe: From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 46 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 18.9 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 28.7 |
Disease Control Rate
Disease control rate was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), or stable disease (SD) lasting ≥ 8 weeks according to International Myeloma Working Group - Uniform Response Criteria (IMWG-URC) (MR was determined using European Group for Blood and Marrow Transplantation criteria). (NCT01080391)
Timeframe: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 87.1 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 92.7 |
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores
Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life. (NCT01080391)
Timeframe: Cycle 1 Day 1 (Baseline), Day 1 of Cycles 3, 6, 12, 18
| Intervention | scores on a scale (Mean) |
|---|
| Cycle 1 Day 1 (Baseline) | Cycle 3, Day 1 | Cycle 6, Day 1 | Cycle 12, Day 1 | Cycle 18, Day 1 |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 58.3 | 59.9 | 62.5 | 62.7 | 64.3 |
,| Lenalidomide and Dexamethasone (Rd) | 58.1 | 56.8 | 58.9 | 57.3 | 59.9 |
Progression-free Survival (PFS)
Kaplan-Meier estimate of median time from randomization to progressive disease (PD) or all-cause death. PD was assessed using International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). One or more conditions were required to meet PD: 2 consecutive rising serum or urine M-protein from central lab; documented new bone lesion(s) or soft tissue plasmacytoma(s) or increased size of existing bone lesion(s) or plasmacytoma(s); or confirmed hypercalcemia due solely to plasma cell proliferative disorder (local lab greater than 11.5 mg/dL on 2 separate occasions). Censoring conditions (censoring dates) were: no post-baseline disease assessment (DA) (randomization date); started non-protocol systemic anticancer treatment before PD or death (last DA date before such treatment); died or had PD after more than 1 missed DA (last DA date without PD before the first missed visit); or were alive and without documentation of PD, including lost to follow-up without PD (last DA date). (NCT01080391)
Timeframe: From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
| Intervention | months (Median) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 17.6 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 26.3 |
Overall Survival
Overall survival (OS) was defined as the duration from randomization to death due to any cause. Participants who were still alive were censored at the date when the participant was last known to be alive or the data cutoff date, whichever occurred earlier. (NCT01080391)
Timeframe: From randomization through the data cutoff date of 28 April 2017 for the final analysis of overall survival; median follow up time was 67.1 months in each treatment group.
| Intervention | months (Median) |
|---|
| Lenalidomide and Dexamethasone (Rd) | 40.4 |
| Carfilzomib, Lenalidomide, and Dexamethasone (CRd) | 48.3 |
Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
(NCT01088048)
Timeframe: pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose | 0.5 hr post-dose | 1.0 hr post-dose | 1.5 hr post-dose | 2.0 hr post-dose | 3.0 hr post-dose | 4.0 hr post-dose | 6.0 hr post-dose |
|---|
| Idelalisib 100 mg (Cohort 1a, 1b) | 1.5 | 437.6 | 1022.4 | 1264.7 | 1282.7 | 1001.0 | 788.4 | 523.7 |
,| Idelalisib 150 mg (Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b) | 0.0 | 1222.1 | 1723.1 | 1599.2 | 1646.2 | 1238.5 | 879.8 | 489.3 |
Plasma Concentration of IDELA (Cohort 7)
(NCT01088048)
Timeframe: Predose, 1.5 hours postdose at Weeks 0, 5 and 13
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | 1.5 hr post-dose (Week 0) | Pre-dose (Week 5) | 1.5 hr post-dose (Week 5) | Pre-dose (Week 13) | 1.5 hr post-dose (Week 13) |
|---|
| Idelalisib 150 mg (Cohort 7) | NA | 1603.1 | 20.7 | 1621.3 | 354.8 | 592.7 |
Plasma Concentration of IDELA (Cohort 6)
(NCT01088048)
Timeframe: Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | 1.5 hr post-dose (Week 0) | Pre-dose (Week 4) | 1.5 hr post-dose (Week 4) | Pre-dose (Week 12) | 1.5 hr post-dose (Week 12) | Pre-dose (Week 24) | 1.5 hr post-dose (Week 24) |
|---|
| Idelalisib 150 mg (Cohort 6) | 0.0 | 1930.7 | 530.8 | 1869.8 | 677.9 | 1733.0 | 346.8 | 1710.7 |
Time to Response
Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR. (NCT01088048)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Idelalisib + Rituximab | 1.9 |
| Idelalisib + Bendamustine | 1.9 |
| Idelalisib + Everolimus | 1.9 |
| Idelalisib + Bortezomib | 1.9 |
| Idelalisib + Rituximab + Bendamustine | 1.9 |
| Idelalisib + Ofatumumab | 1.9 |
| Idelalisib + Fludarabine | 1.9 |
| Idelalisib + Chlorambucil | 1.9 |
| Idelalisib + Rituximab + Chlorambucil | 1.9 |
| Idelalisib + Rituximab + Lenalidomide | 3.0 |
Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
(NCT01088048)
Timeframe: Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | 0.5 hr post-dose (Week 0) | 1.0 hr post-dose (Week 0) | 1.5 hr post-dose (Week 0) | 2.0 hr post-dose (Week 0) | 3.0 hr post-dose (Week 0) | 4.0 hr post-dose (Week 0) | 6.0 hr post-dose (Week 0) | Pre-dose (Week 4) | 1.5 hr post-dose (Week 4) | Pre-dose (Week 12) | 1.5 hr post-dose (Week 12) | Pre-dose (Week 24) | 1.5 hr post-dose (Week 24) |
|---|
| Idelalisib 100 mg (Cohort 1) | 0.4 | 437.6 | 1022.4 | 1434.0 | 1282.7 | 1001.0 | 788.4 | 523.7 | 416.5 | 1297.2 | 361.9 | 1309.5 | 369.9 | 1061.6 |
,| Idelalisib 150 mg (Cohort 5) | 0.0 | 1380.0 | 1600.0 | 1564.7 | 1400.0 | 1170.0 | 795.0 | 517.0 | 408.0 | 1877.9 | 433.9 | 1426.8 | 549.1 | 885.6 |
,| Idelalisib 150 mg (Cohorts 2 and 3) | 68.8 | 1231.4 | 1789.3 | 2017.3 | 1732.8 | 1296.1 | 910.0 | 486.0 | 364.1 | 1808.1 | 351.4 | 1883.0 | 419.7 | 1840.1 |
Progression-free Survival
"Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause.~The response definitions were based on the following standard criteria established for each indication:~CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008~iNHL & MCL: Cheson, 2007" (NCT01088048)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Idelalisib + Rituximab | NA |
| Idelalisib + Bendamustine | NA |
| Idelalisib + Everolimus | 4.3 |
| Idelalisib + Bortezomib | 8.1 |
| Idelalisib + Rituximab + Bendamustine | NA |
| Idelalisib + Ofatumumab | NA |
| Idelalisib + Fludarabine | NA |
| Idelalisib + Chlorambucil | NA |
| Idelalisib + Rituximab + Chlorambucil | NA |
| Idelalisib + Rituximab + Lenalidomide | NA |
Overall Survival
Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause. (NCT01088048)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Idelalisib + Rituximab | NA |
| Idelalisib + Bendamustine | NA |
| Idelalisib + Everolimus | NA |
| Idelalisib + Bortezomib | NA |
| Idelalisib + Rituximab + Bendamustine | NA |
| Idelalisib + Ofatumumab | NA |
| Idelalisib + Fludarabine | NA |
| Idelalisib + Chlorambucil | NA |
| Idelalisib + Rituximab + Chlorambucil | NA |
| Idelalisib + Rituximab + Lenalidomide | NA |
Overall Response Rate
"Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR).~The response definitions were based on the following standard criteria established for each indication:~CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008~iNHL & MCL: Cheson, 2007" (NCT01088048)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Idelalisib + Rituximab | 78.4 |
| Idelalisib + Bendamustine | 84.3 |
| Idelalisib + Everolimus | 44.4 |
| Idelalisib + Bortezomib | 61.1 |
| Idelalisib + Rituximab + Bendamustine | 81.8 |
| Idelalisib + Ofatumumab | 71.4 |
| Idelalisib + Fludarabine | 91.7 |
| Idelalisib + Chlorambucil | 66.7 |
| Idelalisib + Rituximab + Chlorambucil | 93.3 |
| Idelalisib + Rituximab + Lenalidomide | 71.4 |
Duration of Response
Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause. (NCT01088048)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Idelalisib + Rituximab | NA |
| Idelalisib + Bendamustine | NA |
| Idelalisib + Everolimus | 5.6 |
| Idelalisib + Bortezomib | 9.3 |
| Idelalisib + Rituximab + Bendamustine | NA |
| Idelalisib + Ofatumumab | NA |
| Idelalisib + Fludarabine | NA |
| Idelalisib + Chlorambucil | NA |
| Idelalisib + Rituximab + Chlorambucil | NA |
| Idelalisib + Rituximab + Lenalidomide | NA |
Plasma Concentration of Bendamustine
(NCT01088048)
Timeframe: Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | 0.25 hr post-dose (Week 0) | 0.5 hr post-dose (Week 0) | 0.75 hr post-dose (Week 0) | 1.0 hr post-dose (Week 0) | 1.25 hr post-dose (Week 0) | 1.5 hr post-dose (Week 0) | 2.0 hr post-dose (Week 0) | 3.0 hr post-dose (Week 0) | 4.0 hr post-dose (Week 0) | 5.0 hr post-dose (Week 0) | 6.0 hr post-dose (Week 0) |
|---|
| Bendamustine (Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c) | NA | 3484.1 | 4694.7 | 3433.2 | 2847.2 | 1916.4 | 1211.2 | 514.0 | 463.4 | 78.5 | 15.3 | 4.4 |
Plasma Concentration of IDELA (Cohort 4)
(NCT01088048)
Timeframe: Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | Pre-dose (Week 4) | 0.5 hr post-dose (Week 4) | 1.0 hr post-dose (Week 4) | 1.5 hr post-dose (Week 4) | 2.0 hr post-dose (Week 4) | 3.0 hr post-dose (Week 4) | 4.0 hr post-dose (Week 4) | 6.0 hr post-dose (Week 4) | Pre-dose (Week 12) | 1.5 hr post-dose (Week 12) | Pre-dose (Week 24) | 1.5 hr post-dose (Week 24) |
|---|
| Idelalisib 150 mg (Cohort 4) | 0.0 | 0.0 | 1119.5 | 994.5 | 1758.2 | 737.0 | 605.0 | 547.0 | 524.0 | 401.9 | 2018.2 | 752.5 | 2251.1 |
Duration of Exposure to IDELA
Duration of exposure to IDELA was summarized using descriptive statistics. (NCT01088048)
Timeframe: First dose date up to 12 months
| Intervention | months (Mean) |
|---|
| Idelalisib + Rituximab | 8.1 |
| Idelalisib + Bendamustine | 7.6 |
| Idelalisib + Everolimus | 4.2 |
| Idelalisib + Bortezomib | 5.1 |
| Idelalisib + Rituximab + Bendamustine | 8.0 |
| Idelalisib + Ofatumumab | 8.3 |
| Idelalisib + Fludarabine | 8.9 |
| Idelalisib + Chlorambucil | 8.8 |
| Idelalisib + Rituximab + Chlorambucil | 8.7 |
| Idelalisib + Rituximab + Lenalidomide | 7.7 |
Plasma Concentration of Lenalidomide
(NCT01088048)
Timeframe: Predose, 1.5 hours postdose at Week 1 and predose at Week 5
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 1) | 1.5 hr post-dose (Week 1) | Pre-dose (Week 5) |
|---|
| Lenalidomide (Cohort 7a, 7b, 7c) | NA | 51.6 | NA |
Plasma Concentration of Everolimus
(NCT01088048)
Timeframe: Predose, 1.5 hours postdose at Weeks 0 and 4
| Intervention | ng/mL (Mean) |
|---|
| Pre-dose (Week 0) | 1.5 hr post-dose (Week 0) | Pre-dose (Week 4) | 1.5 hr post-dose (Week 4) |
|---|
| Everolimus (Cohort 5a) | NA | 93.0 | 3.0 | 56.3 |
Toxicity of Administration of IDELA
Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02 (NCT01088048)
Timeframe: First dose date up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Idelalisib + Rituximab | 100.0 |
| Idelalisib + Bendamustine | 100.0 |
| Idelalisib + Everolimus | 100.0 |
| Idelalisib + Bortezomib | 83.33 |
| Idelalisib + Rituximab + Bendamustine | 100.0 |
| Idelalisib + Ofatumumab | 100.0 |
| Idelalisib + Fludarabine | 100.0 |
| Idelalisib + Chlorambucil | 100.0 |
| Idelalisib + Rituximab + Chlorambucil | 100.0 |
| Idelalisib + Rituximab + Lenalidomide | 100.0 |
Proportion of Patients Achieving CR
(NCT01093183)
Timeframe: At 4 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide and Cyclophosphamide) | 0 |
Overall Survival
(NCT01093183)
Timeframe: Up to 4 years
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide and Cyclophosphamide) | 20 |
Number of Patients Achieving Objective PSA Response (50% Decrease in PSA Levels Sustained for at Least 4 Weeks) as Defined by PSA Working Group Criteria
(NCT01093183)
Timeframe: 4 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide and Cyclophosphamide) | 7 |
Maximum Tolerated Dose of Lenalidomide Administered in Combination With Oral Cyclophosphamide (Phase I)
Defined to be the dose cohort below which 2 of 3 or 3 of 6 patients experience dose-limiting toxicities in course 1 or the highest dose cohort of 25 mg. (NCT01093183)
Timeframe: 28 days
| Intervention | mg (Number) |
|---|
| Treatment (Lenalidomide and Cyclophosphamide) | 25 |
Percentage of Participants With Overall Survival (OS)
Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization. (NCT01109004)
Timeframe: 38 months post-randomization
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 81.8 |
| RVD Consolidation | 85.4 |
| Lenalidomide Maintenance | 83.7 |
Percentage of Participants With Disease Progression
"Disease Progression is defined as progression of multiple myeloma, including one or more of the following:~A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL~24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours~Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in the serum and urine~At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy~Definite increase in the size of existing bone lesions or soft tissue plasmacytomas~Development of new bone lesions or soft tissue plasmacytomas~Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause~To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk." (NCT01109004)
Timeframe: 38 months post-randomization
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 39.8 |
| RVD Consolidation | 41.0 |
| Lenalidomide Maintenance | 45.6 |
MOS SF-36 Physical Component Summary
The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being. (NCT01109004)
Timeframe: Up to 3 years post-randomization
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 1 Year | 2 Years | 3 Years |
|---|
| Lenalidomide Maintenance | 38 | 42 | 43 | 43 |
,| RVD Consolidation | 39 | 43 | 44 | 42 |
,| Tandem Auto Transplant | 37 | 43 | 44 | 42 |
Number of Participants With Treatment Response
"The number of participants with very good partial response (VGPR) or better [complete response (CR), near CR (nCR), and stringent CR (sCR)] according to the International Uniform Response Criteria will be calculated. The Worse than VGPR group includes PR, stable disease, and progressive disease.~sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: < 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR >=90% reduction in serum PPN plus urine PPN <100 mg/24hrs, >= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either >= 90% or to <200 mg/24 hours in light chain disease, >= 50% reduction in the size of soft tissue plasmacytomas" (NCT01109004)
Timeframe: 1 and 2 years post-randomization
| Intervention | Participants (Count of Participants) |
|---|
| 1 Year72572685 | 1 Year72572686 | 1 Year72572687 | 2 Years72572685 | 2 Years72572687 | 2 Years72572686 |
|---|
| Worse than VGPR | CR or sCR | VGPR or nCR |
|---|
| Tandem Auto Transplant | 97 |
| RVD Consolidation | 122 |
| Lenalidomide Maintenance | 98 |
| Tandem Auto Transplant | 56 |
| RVD Consolidation | 50 |
| Lenalidomide Maintenance | 60 |
| Tandem Auto Transplant | 39 |
| Lenalidomide Maintenance | 50 |
| Tandem Auto Transplant | 98 |
| RVD Consolidation | 117 |
| Lenalidomide Maintenance | 93 |
| RVD Consolidation | 37 |
| Lenalidomide Maintenance | 41 |
| Tandem Auto Transplant | 20 |
| RVD Consolidation | 21 |
| Lenalidomide Maintenance | 26 |
FACT-G Total Score
The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being. (NCT01109004)
Timeframe: Up to 3 years post-randomization
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 1 Year | 2 Years | 3 Years |
|---|
| Lenalidomide Maintenance | 77 | 83 | 85 | 85 |
,| RVD Consolidation | 79 | 84 | 84 | 84 |
,| Tandem Auto Transplant | 79 | 84 | 84 | 85 |
MOS SF-36 Mental Component Summary
The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being. (NCT01109004)
Timeframe: Up to 3 years post-randomization
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 1 Year | 2 Years | 3 Years |
|---|
| Lenalidomide Maintenance | 48 | 50 | 50 | 51 |
,| RVD Consolidation | 48 | 51 | 50 | 50 |
,| Tandem Auto Transplant | 49 | 50 | 50 | 51 |
FACT-BMT Score
The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being. (NCT01109004)
Timeframe: Up to 3 years post-randomization
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 1 Year | 2 Years | 3 Years |
|---|
| Lenalidomide Maintenance | 105 | 113 | 115 | 115 |
,| RVD Consolidation | 107 | 115 | 115 | 114 |
,| Tandem Auto Transplant | 107 | 113 | 114 | 115 |
Percentage of Participants With Progression-free Survival (PFS)
Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization. (NCT01109004)
Timeframe: 38 months post-randomization
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 58.5 |
| RVD Consolidation | 57.8 |
| Lenalidomide Maintenance | 53.9 |
FACT-BMT Trial Outcome Index
The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being. (NCT01109004)
Timeframe: Up to 3 years post-randomization
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 1 Year | 2 Years | 3 Years |
|---|
| Lenalidomide Maintenance | 63 | 71 | 73 | 73 |
,| RVD Consolidation | 65 | 72 | 73 | 71 |
,| Tandem Auto Transplant | 64 | 70 | 73 | 73 |
Overall Response
"Number of patients with a complete or partial response using Cheson criteria for lymphoma.~A complete response is defined as a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy. A partial response is defined as a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Patients who have been on study drug for at least 2 months will be considered evaluable for response as long as they have had repeat imaging to assess response or clear progression based on physical exam." (NCT01121757)
Timeframe: Response will be assessed after at least 4 months on first study drug.
| Intervention | participants (Number) |
|---|
| 1a-Azacitidine Followed by Lenalidomide | 1 |
| 1b-Lenalidomide Followed by Azacitidine | 0 |
Response Predicted by Molecular Signatures Compared to True Response
"The predicted response (response to therapy vs. no response to therapy) using gene sequencing will be compared to the overall true response (reported in Primary Outcome 2)." (NCT01121757)
Timeframe: approximately one year
| Intervention | participants (Number) |
|---|
| Predicted: Response; Actual: Response | Predicted: No Response; Actual: No Response | Predicted: Response; Actual: No Response |
|---|
| 1a-Azacitidine Followed by Lenalidomide | 1 | 2 | 3 |
,| 1b-Lenalidomide Followed by Azacitidine | 0 | 3 | 0 |
Number of Participants With Grade 3 and 4 Toxicities
Evaluate the safety of lenalidomide, azacitidine and the combination of azacitidine + lenalidomide in patients with lymphoma; grading the adverse events using Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 (NCT01121757)
Timeframe: While taking the study drug and 30 days after the last dose
| Intervention | participants (Number) |
|---|
| Grade 3 | Grade 4 |
|---|
| 1a-Azacitidine Followed by Lenalidomide | 5 | 1 |
,| 1b-Lenalidomide Followed by Azacitidine | 3 | 1 |
Overall Response
"Number of patients with a complete or partial response using Cheson criteria for lymphoma.~A complete response is defined as a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy. A partial response is defined as a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Patients who have been on study drug for at least 2 months will be considered evaluable for response as long as they have had repeat imaging to assess response or clear progression based on physical exam." (NCT01121757)
Timeframe: Response will be assessed after at least 4 months on second drug.
| Intervention | participants (Number) |
|---|
| 1a-Azacitidine Followed by Lenalidomide | 2 |
| 1b-Lenalidomide Followed by Azacitidine | 0 |
Frequency of Adverse and Severe Adverse Events
Frequency of adverse and severe adverse events (NCT01123356)
Timeframe: 30 weeks
| Intervention | participants (Number) |
|---|
| Number of SAEs | Neutropenia | grade 3/4 neutropenia | thrombocytopenia | grade 3/4 thrombocytopenia | tumor flare reaction | grade 3 tumor flare reaction |
|---|
| Oratumumab and Lenalidomide | 4 | 19 | 10 | 15 | 4 | 9 | 1 |
Dose Reductions Due to Adverse Events.
Number of dose reductions due to toxicity. (NCT01123356)
Timeframe: 30 weeks
| Intervention | dose reductions (Number) |
|---|
| Oratumumab and Lenalidomide | 17 |
Frequency of Adverse Events
Number of adverse events occuring in greater than 20% of subjects (NCT01123356)
Timeframe: 30 weeks
| Intervention | events (Number) |
|---|
| Oratumumab and Lenalidomide | 15 |
Overall Response Rate
"Obtain early assessment of the efficacy of the intracycle sequential administration of ofatumumab and lenalidomide in the treatment of chronic lymphocytic leukemia (CLL) after prior use of rituximab. Response was categorized according to the IW-CLL criteria which includes the following: Complete remission (CR), CR with incomplete marrow recovery (CRi)Partial remission (PR), Progressive disease (PD), Stable disease (SD).~Overall response rate was defined as those who experienced a response of CR, CRi or PR." (NCT01123356)
Timeframe: 30 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Oratumumab and Lenalidomide | 53 |
Time to Response
Measured from time of study drug administration to initial response (partial or complete), measured in months. (NCT01125176)
Timeframe: From date of study drug initiation to date of initial response, assessed up to 12 months.
| Intervention | months (Median) |
|---|
| All Subjects | 10 |
Overall Survival
Measured from time of study drug administration to death, measured in months. (NCT01125176)
Timeframe: From date of study drug initiation to date of death, assessed through study completion up to 105 months.
| Intervention | months (Median) |
|---|
| All Subjects | 97 |
Progression Free Survival
Measured from time of study drug administration to progression or death, measured in months. (NCT01125176)
Timeframe: From date of study drug initiation until date of progression or death, whichever occurs first, assessed through study completion up to 100 months.
| Intervention | months (Median) |
|---|
| All Subjects | 48 |
Overall Response Rate as Defined as the Number of Patients Who Experience a Response (Complete or Partial) to Treatment at the Time of Best Response
Response will be evaluated in this study using the International Workshop on CLL (IWCLL) update of the 1996 NCI-Working Group criteria for CLL, which includes assessment of the following: clonal lymphocytes in the peripheral blood by flow cytometry, blood tests for neutrophil count, hemoglobin, and platelet count, CT examination for lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms, bone marrow assessment via biopsy/aspirate, and evaluation for disease transformation. (NCT01125176)
Timeframe: From date of study drug initiation until date of best response, assessed up to 6 years.
| Intervention | Participants (Count of Participants) |
|---|
| All Subjects | 12 |
Duration of Response
Measured from end of treatment to progression or death, measured in months. (NCT01125176)
Timeframe: From date of end of treatment to progression or death, whichever occurs first, assessed through study completion up to 100 months.
| Intervention | months (Median) |
|---|
| All Subjects | 70 |
Number of Participants With Erythroid Response
The rate of erythroid response to treatment with the lenalidomide/prednisone combination in non-del (5q) low and int-1 risk Myelodysplastic Syndrome (MDS) with symptomatic anemia. Hematological improvement erythroid response (HI-E) according to International Working Group (IWG) 2006 criteria. (NCT01133275)
Timeframe: Up to 7 months
| Intervention | participants (Number) |
|---|
| Lenalidomide and Prednisone Therapy | 5 |
Correlate the Presence of Specific Fc RIIIa Polymorphisms With Progression-free Survival in Subjects Receiving Cetuximab and Lenalidomide for SCCHN.
Progression-free survival (PFS) was defined as time from date of the first treatment dose administered to the earlier of disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01133665)
Timeframe: 24 months
| Intervention | months (Median) |
|---|
| Cetuximab and Lenalidomide | 1.8 |
Phase I: Number of Patients With Dose Limiting Toxicity
The number of patients who had a DLT during the dose finding portion (Phase I) of the trial for the safety of lenalidomide when used in combination with high dose melphalan in the setting of autologous stem cell transplantation in patients with multiple myeloma. (NCT01142232)
Timeframe: up to 1 month
| Intervention | Participants (Count of Participants) |
|---|
| Phase I, Dose Level 1 | 0 |
| Phase I, Dose Level 2 | 0 |
| Phase I, Dose Level 3 | 0 |
| Phase I, Dose Level 4 | 0 |
Phase II: Overall Response Rate
Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better (CR+sCR+VGPR+PR). The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the response criteria determined by the International Working Group for Multiple Myeloma (CR= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow; sCR=CR as defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunoflurorescence; VGPR=Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component<100 mg per 24 h; PR=>=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by >=90% or to <200mg per 24 h). (NCT01142232)
Timeframe: up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Phase II | 87.5 |
Number of Participants Who Achieved a Complete Response
Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. (NCT01145495)
Timeframe: At 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide, Rituximab) | 47 |
Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Data will be summarized using frequency tables. (NCT01145495)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1-2 Fatigue | Grade 1-2 Diarrhea | Grade 1-2 Rash | Grade 1-2 Febrile neutropenia | Grade 3-4 Neutropenia | Grade 3-4 Lymphopenia | Grade 3-4 Thrombocytopenia | Grade 3-4 Infection | Grade 3-4 Rash |
|---|
| Treatment (Lenalidomide, Rituximab) | 51 | 24 | 21 | 1 | 14 | 6 | 1 | 7 | 5 |
Disease Progression
Kaplan-Meier method will be used. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01145495)
Timeframe: Up to 5 years
| Intervention | proportion of participants (Number) |
|---|
| 2 Years PFS | 3 Years PFS | 4 Years PFS | 5 Years PFS |
|---|
| Treatment (Lenalidomide, Rituximab) | 0.86 | 0.81 | 0.74 | 0.72 |
Percent of Participants With Clinical Benefit and Response According to International Response Criteria
Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. (NCT01155583)
Timeframe: at 6 months
| Intervention | percentage of participants (Number) |
|---|
| international response criteria (>= PR) | clinical benefit response (>= minor response) |
|---|
| Overall Study - (Azacitidine/Lenalidomide/Dexamethasone) | 20 | 32 |
,| Participants Who Received HTLD/HTLD-CKD | 23 | 32 |
Percent of Participants With Clinical Benefit and Response According to International Response Criteria
Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. (NCT01155583)
Timeframe: at 12 months
| Intervention | percentage of participants (Number) |
|---|
| International response criteria (>= PR) | clinical benefit response (>= minor response) |
|---|
| Overall Study - (Azacitidine/Lenalidomide/Dexamethasone) | 22 | 32 |
,| Participants Who Received HTLD/HTLD-CKD | 23 | 32 |
Phase I: Highest Tolerated Low Dose (HTLD)
Azacitidine given at low but increasing doses up to 50mg/m2 twice a week. Maximum tolerated dose reported. (NCT01155583)
Timeframe: During the first 28-day cycle
| Intervention | mg/m^2 (Number) |
|---|
| Arm A - Azacitidine/Lenalidomide/Dexamethasone | 50 |
| Arm B - CKD Azacitidine/Lenalidomide/Dexamethasone | 50 |
Overall Survival
Overall survival will be measured from study entry to death from any cause - median months survival will be reported (NCT01155583)
Timeframe: up to 3 years
| Intervention | months (Median) |
|---|
| Overall Study - (Azacitidine/Lenalidomide/Dexamethasone) | 18.6 |
Follow-up Time
time that patients were monitored for disease progression and overall survival (NCT01160484)
Timeframe: Follow-up visits for disease progression and overall survival every 3 months after study discontinuation. After progression, follow-up visits for survival status every 6 months or until alternate therapy needs to be started or death intervenes
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 11 |
Progression-free Survival
(NCT01160484)
Timeframe: Time from the start of treatment to progressive disease or until death
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 9 |
Duration of Response
(NCT01160484)
Timeframe: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 12 |
Time to Best Response
(NCT01160484)
Timeframe: Up to 7.5 months (eight 28-day cycles)
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 2 |
Time to First Response
(NCT01160484)
Timeframe: Up to 7.5 months (eight 28-day cycles)
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 1 |
Time to Progression
(NCT01160484)
Timeframe: Time from the start of treatment to progressive disease
| Intervention | months (Median) |
|---|
| DVD-R Single Arm | 9 |
International Myeloma Working Group (IMWG) Response Criteria
The investigator will evaluate each patient for response to therapy according to criteria augmented from those developed by Bladé et al., 1998 presented below (Table 7-1). Assessment of disease response will be performed prior to drug administration on Day 1 of Cycles 2 8 and at the End of Study Treatment visit. If a patient is determined to have complete response (CR), very good partial response (VGPR), partial response (PR), or minor response (MR), then assessment of disease response is to be performed 4 weeks later to confirm the response. (NCT01160484)
Timeframe: Up to 7.5 months (eight 28-day cycles)
| Intervention | participants (Number) |
|---|
| CR | VGPR | PR | Objective Response (CR+VGPR+PR) | MR | Clinical Benefit (CR+VGPR+PR+MR) | Estable disease | Progressive disease |
|---|
| DVD-R Single Arm | 8 | 4 | 7 | 19 | 14 | 33 | 4 | 2 |
Proportion of Participants With Response (Phase III Secondary Endpoint)
"Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR).~CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours~PR:~≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours~If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels~If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30%~If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas" (NCT01169337)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase III) | 0.50 |
| Arm B (Observation; Phase III) | 0 |
Proportion of Patients With Grade 3 Adverse Events That Effect Vital Organ Function or Any Grade 4 or Higher Non-hematologic Adverse Events (Phase II Primary Endpoint)
Proportion of patients with grade 3 adverse events that effect vital organ function (such as cardiac, hepatic or thromboembolic) or any grade 4 or higher non-hematologic adverse events (NCT01169337)
Timeframe: Assessed every 4 weeks while on treatment up to 24 weeks
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase II) | 0.056 |
1-year Progression-free Survival (PFS) Rate (Phase III Secondary Endpoint)
"PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 1-year PFS rate.~Any of the following:~Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as progression~Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as progression~Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%)~Any of the following felt related to the underlying clonal plasma cell proliferative disorder:~Hypercalcemia (> 11 mg/dL)~Decrease in hemoglobin of ≥ 2 gms/dL~Serum creatinine level ≥ 2mg/dL~Development of myeloma bone lesions or soft tissue plasmacytoma" (NCT01169337)
Timeframe: Assessed every 3 months for one year
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase III) | 0.98 |
| Arm B (Observation; Phase III) | 0.89 |
2-year Overall Survival (OS) Rate (Phase III Secondary Endpoint)
Overall survival is defined as the time from randomization to death or date last known alive among all randomized patients in the phase III part of the study. Kaplan-Meier method was used to estimate the 2-year OS rate. (NCT01169337)
Timeframe: Assessed every 3 months for 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase III) | 0.98 |
| Arm B (Observation; Phase III) | 1.00 |
2-year Progression-free Rate (Phase III Secondary Endpoint)
"TTP is defined as the time from randomization to progression. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year progression-free rate.~Any of the following:~Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as progression~Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as progression~Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%)~Any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder:~Hypercalcemia (> 11 mg/dL)~Decrease in hemoglobin of ≥ 2 gms/dL~Serum creatinine level ≥ 2mg/dL~Development of myeloma bone lesions or soft tissue plasmacytoma" (NCT01169337)
Timeframe: Assessed every 3 months for 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase III) | 94.3 |
| Arm B (Observation; Phase III) | 75.8 |
2-year Progression-free Survival (PFS) Rate (Phase III Primary Endpoint)
"PFS is defined as time from randomization to progression or death, whichever occurs first. Patients are considered to have progression if both of the following criteria are met. Kaplan-Meier method was used to estimate 2-year PFS rate.~Any of the following:~Increase in serum M-protein to ≥ 25% above the lowest response level with an absolute increase of at least 0.5g/dl to qualify as progression~Increase in urine M-protein to ≥ 25% above the lowest response level for 24-hour excretion with an absolute increase of at least 200mg/24 hours of urine M-protein to qualify as progression~Increase in bone marrow plasma cell percentage to ≥ 25% from lowest response value (the absolute % increase must be ≥ 10%)~Any of the following felt related to the underlying clonal plasma cell proliferative disorder:~Hypercalcemia (> 11 mg/dL)~Decrease in hemoglobin of ≥ 2 gms/dL~Serum creatinine level ≥ 2mg/dL~Development of myeloma bone lesions or soft tissue plasmacytoma" (NCT01169337)
Timeframe: Assessed every 3 months for 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase III) | 0.93 |
| Arm B (Observation; Phase III) | 0.76 |
Proportion of Participants With Response (Phase II Secondary Endpoint)
"Response is defined as complete response (CR), very good partial response (VGPR) or partial response (PR).~CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-component plus urine M-component < 100 mg per 24 hours~PR:~≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours~If followed by free light chain (FLC) only, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels~If unmeasurable disease by serum M-protein, urine M-protein, and serum FLC at baseline, a ≥50% reduction in plasma cells provided baseline bone marrow percentage was ≥ 30%~If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas" (NCT01169337)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then annually for years 6-10
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide; Phase II) | 0.477 |
Stage 1: Percentage of Participants With an Overall Response According to the IWG Response Criteria Based on the Investigators Assessment at the Final Data Cut During the Core Treatment Phase
Response was defined as having a CR, CRu or PR, based on IWG 1999 Response Criteria for NHL as evaluated by the investigators. CR = complete disappearance of disease and disease related symptoms. All lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical exam, normal size by imaging, and absence of nodules related to lymphoma. If BM was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new disease. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Percentage of participants (Number) |
|---|
| Lenalidomide | 29.4 |
| Investigators Choice (IC) | 13.7 |
Stage 1: Percentage of Participants With a Complete Response According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
A complete response was defined as participants with a complete response (CR), or unconfirmed complete response (CRu) based on IWG 1999 Response Criteria for NHL as assessed by the investigator. A CR is a complete disappearance of all disease with the exception of nodes. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRu) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 13.7 |
| Investigators Choice (IC) | 3.9 |
Stage 1: Kaplan Meier Estimates of Overall Survival As Assessed by the Investigators at the Final Data Cut During The Core Treatment Phase
Overall survival was defined as time from randomization until death of any cause. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 31.0 |
| Investigators Choice (IC) | 24.6 |
Number of Participants With Treatment Emergent Events (TEAEs) in the Overall Treatment Phase by Initial Treatment Assignment
"A TEAE was defined as an AE that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.~A serious adverse event (SAE) is any:~Death;~Life-threatening event;~Any inpatient hospitalization or prolongation of existing hospitalization;~Persistent or significant disability or incapacity;~Congenital anomaly or birth defect;~Any other important medical event The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event.The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death" (NCT01197560)
Timeframe: From first dose of study drug to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAEs | Any Treatment Related TEAE | Any TEAE Grade ≥ 3 | Any TEAE Grade ≥ 4 | Any TEAE Grade 5 | Any TEAE Grade 3 or 4 | Any Treatment Related TEAE Grade ≥ 3 | Any Treatment Related TEAEs Grade ≥ 4 | Any Treatment Related TEAE Grade 5 | Any Treatment Related TEAE Grade 3 or 4 | Any Serious Adverse Events (SAEs) | Any Treated Related SAEs | Any AE leading to stopping of study drug | Any drug related AE leading to halt of study drug | Any AE leading to dose interruption/reduct | Any drug related AE leading to interruption/reduct |
|---|
| Investigators Choice (IC) | 55 | 45 | 53 | 36 | 18 | 52 | 39 | 21 | 2 | 39 | 42 | 21 | 17 | 4 | 34 | 30 |
,| Lenalidomide | 54 | 49 | 43 | 29 | 9 | 42 | 30 | 15 | 0 | 30 | 31 | 14 | 11 | 5 | 32 | 27 |
Stage 1: Percentage of Participants With an Overall Response According to the International Working Group (IWG) Response Criteria for Non Hodgkin's Lymphoma (NHL), Cheson 1999 and Evaluated by the Independent Response Adjudication Committee (IRAC)
An overall response is a complete response (CR), unconfirmed complete response (CRu) or partial response (PR) and was evaluated by the IRAC. A CR = complete disappearance of disease and related symptoms. Lymph nodes and nodal masses regressed on computed tomography to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on exam, normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter;no new disease. (NCT01197560)
Timeframe: From the date of randomization to the data cut-off of 4 July 2013; when all patients reached the scheduled 16-week assessment or had progressed/died before the scheduled 16-week assessment); the median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | percentage of participants (Number) |
|---|
| ORR for All Participants | GCB Subtype | Non-GCB |
|---|
| Investigators Choice (IC) | 11.8 | 12.0 | 11.5 |
,| Lenalidomide | 27.5 | 26.1 | 28.6 |
Stage 1: Percentage of Participants With a Durable Overall Response (dORR) According to the IWG Response Criteria as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Durable overall response rate was defined as the percentage of participants who maintained a response for at least 16 weeks after initial response. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | percentage of participants (Median) |
|---|
| Lenalidomide | 23.5 |
| Investigators Choice (Control Arm) | 9.8 |
Stage 1: Kaplan Meier Estimates of Progression-Free Survival As Assessed By The Investigators At The Final Data Cut During The Core Treatment Phase
Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 9.6 |
| Investigators Choice (IC) | 7.1 |
Stage 1: Kaplan Meier Estimates of Duration of Overall Response (DoR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Duration of overall response was calculated as the time of initial response (CR+CRu+PR) until documented disease progression determinted by computerized scan CT scan or MRI or death due to lymphoma, whichever occurred earlier, for participants who responded. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 64.7 |
| Investigators Choice (Control Arm) | 63.1 |
Stage 1: Kaplan Meier Estimates of Duration of Complete Response (DoCR) as Assessed by the Investigators at the Final Data Cut During the Core Treatment Phase
Duration of complete response was defined as the time from the first documented complete response (CR + CRu) until the first disease progression or death for participants who had a CR. (NCT01197560)
Timeframe: From the date of randomization to the final data cut-off date of 18 May 2018; median study duration was 27.0 and 19.7 weeks, respectively.
| Intervention | Weeks (Median) |
|---|
| Lenalidomide | 66.4 |
| Investigators Choice (Control Arm) | 179.3 |
Overall Response Rate (ORR)
(NCT01199575)
Timeframe: nine months
| Intervention | Participants (Count of Participants) |
|---|
| Revlimid + Rituximab | 25 |
Adverse Events to Study Treatment
(NCT01199575)
Timeframe: one year
| Intervention | Participants (Count of Participants) |
|---|
| Revlimid + Rituximab | 25 |
Overall Survival (Final Results After Crossover)
Time from randomization to death from any cause. Patients who have not died are censored as of the date last known alive. (NCT01208051)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| Dose Level 0 | NA |
| Dose Level +1 | 60.0 |
| Dose Level +2 | 100 |
| Phase II Arm A (Cediranib Maleate) | 64.8 |
| Phase II Arm B (Cediranib Maleate Plus Lenalidomide) | 75.3 |
Percent Change in Tumor Size (Phase II)
The percent change in tumor size from baseline to the end of cycle 2 (two months). The post-treatment total sum of lengths for a patient with a new lesion at cycle 2 will be scored as 1.2*max(pre-sum, post-sum) to ensure that the appearance of new lesions corresponds to a disease progression per Response Evaluation Criteria in Solid Tumors criteria. In the event of any early deaths prior to cycle 2, a nonparametric rank sum test will be used with deaths ranked at the extreme end of the distribution. (NCT01208051)
Timeframe: From baseline to 2 months
| Intervention | percent change (Median) |
|---|
| Phase II Arm A (Cediranib Maleate) | -12.5 |
| Phase II Arm B (Cediranib Maleate Plus Lenalidomide) | -4.2 |
Progression-free Survival (Final Results After Crossover)
Time from study enrollment until disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01208051)
Timeframe: Assessed up to 3 years
| Intervention | months (Median) |
|---|
| Dose Level 0 | NA |
| Dose Level +1 | 14.8 |
| Dose Level +2 | 23.6 |
| Phase II Arm A (Cediranib Maleate) | 14.8 |
| Phase II Arm B (Cediranib Maleate Plus Lenalidomide) | 11.3 |
Progression-free Survival (Phase II Futility Analysis)
Time from enrollment on study to disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This analysis corresponds to the planned futility analysis after 40 events. (NCT01208051)
Timeframe: Assessed up to 3 years
| Intervention | months (Median) |
|---|
| Phase II Arm A (Cediranib Maleate) | 20.9 |
| Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015) | 10.6 |
Dose Limiting Toxicity
"Dose limiting toxicity was defined as any of the following occurring during the first cycle (28 days) of therapy:~Hematological toxicities:~Any grade 4 neutropenia (ANC < 500) lasting more than 5 days~Any grade 4 neutropenia with concomitant fever (temperature > 38.5)~Any grade 4 neutropenia and sepsis or other severe infection~Any grade 4 thrombocytopenia~Any other grade 3-4 non-hematological adverse drug reactions, except untreated nausea/vomiting, or hypersensitivity reactions.~Grade 4 hypertension~Grade 4 proteinuria Delay in the administration of a subsequent dose of cediranib and lenalidomide exceeding 2 weeks, due to an adverse drug reaction" (NCT01208051)
Timeframe: 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Dose Level 0 | 0 |
| Phase I Dose Level +1 | 1 |
| Phase I Dose Level +2 | 2 |
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01208051)
Timeframe: Assessed up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Dose Level 0 | 0 |
| Dose Level +1 | 2 |
| Dose Level +2 | 4 |
| Phase II Arm A (Cediranib Maleate) | 17 |
| Phase II Arm B (Cediranib Maleate Plus Lenalidomide) | 30 |
5-Year Overall Survival (OS)
OS was estimated using the KM method and defined as time from randomization to death due to any cause. Patients alive were censored at date last known alive. The 5-year OS endpoint is a probability. (NCT01208662)
Timeframe: In long-term follow-up, survival follow-up every 2 months until death. Median (maximum) OS follow-up was 76 and 129 months.The probability estimate is at 5 years.
| Intervention | percent probability (Number) |
|---|
| RVD Alone | 79.2 |
| RVD Plus ASCT | 80.7 |
Partial Response (PR) Rate
The PR rate is the percentage of participants achieving PR or better on treatment and was evaluated based on the IMWG criteria. PR was defined as > 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by > 90% or to < 200mg per 24 hours. If the serum and urine M-protein are unmeasurable, a > 50% decrease in the difference between involved and uninvolved free light chain levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was > 30%. In addition to the above listed criteria, if present at baseline, a > 50% reduction in the size of soft tissue plasmacytomas was also required. Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes. (NCT01208662)
Timeframe: Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 133.5 months in this study cohort.
| Intervention | percentage of participants (Number) |
|---|
| RVD Alone | 95 |
| RVD Plus ASCT | 97.5 |
5-Year Time to Progression (TTP)
TTP was estimated using the KM method and defined as time from randomization to time of documented IMWG disease progression or censoring time (time of last disease evaluation for those alive, time to death among those who died). Patients initiating non-protocol therapy prior to progression or death were censored at the date of non-protocol therapy in the TTP analysis. The 5-year TTP endpoint is a probability. (NCT01208662)
Timeframe: On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median TTP follow-up was 70 months. The probability estimate is at 5 years.
| Intervention | percent probability (Number) |
|---|
| RVD Alone | 41.6 |
| RVD Plus ASCT | 58.4 |
Change From Baseline on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX)
The FACT/GOG-NTX assessment consists of 11 questions that are all used to construct 1 subscale to summarize symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. (https://www.facit.org/measures/FACT-GOG-NTX) Each question has 4 possible responses from 0 (Not at all) to 4 (Very Much) which are reverse-scored and summed. This sum is then scaled by the number of questions answered by multiplying by 11 and then dividing by the number of questions that are non-blank, in order to keep all final scores proportional to one another even if some questions are left blank. The aggregate score ranges from 0 to 44, with higher scores indicating less neurotoxicity and lower scores indicating more neurotoxicity. Change from baseline is the difference (NCT01208662)
Timeframe: Cycle 1 (Baseline), Cycle 2, Pre-Mobilization, Cycle 5 Arm A / Post Auto-HSCT Arm B, Cycle 8 Arm A /Cycle 5 Arm B, Maintenance Day 1, 2 years from baseline, 3 years from baseline
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2 | Pre-Mobilization | Cycle 5 Arm A / Post Auto-HSCT Arm B | Cycle 8 Arm A /Cycle 5 Arm B | Maintenance Day 1 | 2 years from baseline | 3 years from baseline |
|---|
| RVD Alone | -1.8 | -3.9 | -4.4 | -4.7 | -3.7 | -4.9 | -4.6 |
,| RVD Plus ASCT | -1.3 | -3.5 | -4.4 | -2.5 | -2.3 | -2.6 | -3.2 |
Median Maintenance Treatment Duration
Maintenance treatment duration estimated using the KM method is defined as the time from start of maintenance to the time off maintenance (event) or censored at date of last maintenance treatment. (NCT01208662)
Timeframe: Up to 128 months
| Intervention | months (Median) |
|---|
| RVD Alone | 36.4 |
| RVD Plus ASCT | 41.5 |
Quality-Adjusted Life Years (QALYs)
QALYs were estimated with a model beginning at initiation of first-line therapy by arm. A lifetime horizon, as well as subsequent lines of therapy, was examined using open-source Amua 0.3.0 software. Base case analysis was performed using 10,000 first-order Monte Carlo simulations. Conditional probabilities were extracted from Kaplan-Meier curves from pivotal clinical trials using WebPlotDigitizer. Costs were estimated from RED BOOK and DFCI charge reporting in US Dollars ($) after inflation adjustment to 2022 and 3% discounting, and QALYs effects were measured using EQ-5D data from Hatswell et al. (NCT01208662)
Timeframe: Maximum observation of survival for this study cohort was 129.4 months.
| Intervention | years gained (Mean) |
|---|
| RVD Alone | 5.67 |
| RVD Plus ASCT | 6.10 |
5-year Cumulative Incidence of Second Primary Malignancy (SPM)
Second primary malignancy (SPM) is defined as the development of another new, unrelated cancer, regardless of treatment for previous malignancy attribution. The cumulative incidence of SPMs was estimated with death as a competing risk. SPMs were collected using an SAE form or MEDWATCH 3500A form, with intensity determined by using the NCI CTCAE version 4 as a guideline. (NCT01208662)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| RVD Alone | 4.9 |
| RVD Plus ASCT | 6.5 |
Subsequent Therapy Rate
Subsequent therapy rate was the percentage of participants who discontinued treatment and initiated subsequent non-protocol therapy. (NCT01208662)
Timeframe: Up to 129 months
| Intervention | Participants (Count of Participants) |
|---|
| RVD Alone | 222 |
| RVD Plus ASCT | 192 |
Very Good Partial Response (VGPR) Rate
The VGPR rate is the percentage of participants achieving VGPR or better on treatment and was evaluated based on IMWG criteria. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hours. (NCT01208662)
Timeframe: Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.
| Intervention | percentage of patients (Number) |
|---|
| RVD Alone | 79.6 |
| RVD Plus ASCT | 82.7 |
Change From Baseline on the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30): Global Health Status/Quality of Life (QoL) Sub-scale
The EORTC QLQ-C30 assessment consists of 30 questions that are used to construct 15 distinct sub-scales (five function scales, nine symptom scales, and a global health status/QoL scale). The global health status/QoL scale is comprised of two questions each with a range of 6 (1=Very Poor to 7=Excellent). Scores on all sub-scales range from 0 to 100 after linear transformation of the raw scores, with higher scores representing better global health status and quality of life. (NCT01208662)
Timeframe: Cycle 1 (Baseline), Cycle 2, Pre-Mobilization, Cycle 5 Arm A / Post Auto-HSCT Arm B, Cycle 8 Arm A /Cycle 5 Arm B, Maintenance Day 1, 2 years from baseline, 3 years from baseline
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2 | Pre-Mobilization | Cycle 5 Arm A / Post Auto-HSCT Arm B | Cycle 8 Arm A /Cycle 5 Arm B | Maintenance Day 1 | 2 years from baseline | 3 years from baseline |
|---|
| RVD Alone | 0.1 | 0.4 | 3.0 | 1.2 | 5.3 | 5.1 | 3.5 |
,| RVD Plus ASCT | 4.3 | 4.4 | -11.1 | 8.3 | 9.9 | 11.1 | 12.7 |
Next Generation Sequencing (NGS) Minimal Residual Disease Negative (MRD-) Rate at Maintenance Start
Bone marrow aspirate samples were obtained from patients prior to the start of lenalidomide maintenance. NGS MRD- rate is the percentage of evaluable participants with MRD level of <1 x 10-5 (indicating detection of 1 malignant plasma cell in 100,000 bone marrow cells) using the validated, US Food and Drug Administration approved clonoSEQ® NGS platform (Adaptive Biotechnologies) with a minimum sensitivity of 1 x 10-5. (NCT01208662)
Timeframe: Maintenance treatment occurred after induction, up to 11.5 months.
| Intervention | percentage of participants (Number) |
|---|
| RVD Alone | 39.8 |
| RVD Plus ASCT | 54.4 |
Complete Response (CR) Rate
The CR rate is the percentage of participants achieving CR or better on treatment and was evaluated based on IMWG criteria. CR was defined as the negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Confirmation with repeat bone marrow biopsy was not needed. (NCT01208662)
Timeframe: Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.
| Intervention | percentage of patients (Number) |
|---|
| RVD Alone | 42.0 |
| RVD Plus ASCT | 46.8 |
The Percent of Patients With Minimal Residual Disease (MRD) Status Changing to Negative at Day 100 (Post-AHCT), Among Patients With MRD Positive at the End of Induction (EOI).
Patients were treated with induction therapy (VRD) followed by autologous hematopoietic cell transplant (AHCT). MRD status of a patient with at least partial response was evaluated at the end of induction (EOI) and day 100 (post-AHCT). MRD of a patient is measured by seven-color flow cytometry. (NCT01215344)
Timeframe: 6-months post ASCT
| Intervention | percentage of participants (Number) |
|---|
| VELCADE, Lenalidomide, Dexamethasone (VRD) | 30 |
Progression Free Survival by MRD Status at Day 100.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT01215344)
Timeframe: up to 7 years
| Intervention | years (Median) |
|---|
| MRD Negative at Day 100 | 2.64 |
| MRD Status Positive at Day 100 (Post-AHCT) | NA |
3-year Progression-free Survival Rate
"Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.~Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis." (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | proportion of participants (Number) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 0.77 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 0.82 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 0.76 |
1-year Post-induction Disease-free Survival (DFS) Rate
"1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.~The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis." (NCT01216683)
Timeframe: Assessed at 1 year post-induction, approximately 1.5 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 0.85 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 0.67 |
1-year Disease-free Survival (DFS) Rate
"1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.~This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients disease-free and alive at 1 year post induction treatment was compared between patients with CIRS <10 and patients with CIRS >=10. Higher CIRS scores indicate higher severity with max score of 56 points." (NCT01216683)
Timeframe: Assessed at 1 year post-induction, approximately 1.5 years
| Intervention | proportion of participants (Number) |
|---|
| CIRS <10 | 0.62 |
| CIRS >=10 | 0.65 |
1-year Disease-free Survival (DFS) Rate
"1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.~This analysis was conducted among 203 evaluable patients in the continuation treatment portion of the study. The 1-year post induction disease-free survival rate was compared between patients with FLIPI of 3-5 and patients with FLIPI of 0-2/unknown.~The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis." (NCT01216683)
Timeframe: Assessed at 1 year post-induction, approximately 1.5 years
| Intervention | proportion of participants (Number) |
|---|
| FLIPI 0-2/Unknown | 0.84 |
| FLIPI 3-5 | 0.74 |
Complete Remission (CR) Rate
"Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.~This analysis was conducted among 222 evaluable patients. The proportion of patients with complete remission was compared between patients with Follicular Lymphoma International Prognostic Index (FLIPI) of 3-5 and patients with FLIPI of 0-2/unknown.~The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis." (NCT01216683)
Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
| Intervention | proportion of participants (Number) |
|---|
| FLIPI 0-2/Unknown | 0.71 |
| FLIPI 3-5 | 0.64 |
Complete Remission (CR) Rate
"Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.~This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients with complete remission was compared between patients with CIRS <10 and patients with CIRS >=10. Higher CIRS scores indicate higher severity with max score of 56 points." (NCT01216683)
Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
| Intervention | proportion of participants (Number) |
|---|
| CIRS <10 | 0.70 |
| CIRS >=10 | 0.70 |
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Baseline
The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at baseline
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 83.9 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 84.7 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 86.0 |
Complete Remission (CR) Rate
"Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.~This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine)." (NCT01216683)
Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A and Arm C (Induction With Bendamustine + Rituximab) | 0.62 |
| Arm B (Induction With Bendamustine + Rituximab + Bortezomib) | 0.75 |
Proportion of Patients With Grade 3 or Higher Peripheral Neuropathy
Peripheral neuropathy was assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Proportion of patients with grade 3 or higher peripheral neuropathy was compared between patients with subcutaneous bortezomib and patients with intravenous bortezomib. (NCT01216683)
Timeframe: Assessed every cycle during treatment and for 30 days after discontinuation of treatment, up to 15 years
| Intervention | proportion of participants (Number) |
|---|
| Subcutaneous Bortezomib | 0.06 |
| Intravenous Bortezomib | 0.12 |
5-year Overall Survival Rate
Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier. (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | proportion of participants (Number) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 0.87 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 0.86 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 0.83 |
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at the End of Induction Treatment
The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at end of induction treatment (cycle 6), approximately 6 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 39.8 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 36.1 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 39.0 |
Progression-free Survival
"Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.~The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis." (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | years (Median) |
|---|
| FLIPI 0-2/Unknown | 6.1 |
| FLIPI 3-5 | 6.2 |
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Mid-induction Treatment
"The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.~FACIT-Fatigue subscale score at cycle 3 is considered as mid-treatment score. If FACIT-Fatigue subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score." (NCT01216683)
Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 39.2 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 34.5 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 36.3 |
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at End of Induction Treatment
The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at cycle 6, approximately 6 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 39.9 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 39.1 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 36.3 |
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at End of Induction Treatment
The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at cycle 6, approximately 6 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 86.0 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 86.5 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 84.9 |
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Baseline
The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at baseline
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 43.8 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 44.3 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 44.9 |
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at End of Induction Treatment
The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at cycle 6, approximately 6 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 48.9 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 48.4 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 47.2 |
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Baseline
The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at baseline
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 38.6 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 37.9 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 38.1 |
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Mid-induction Treatment
"The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.~FACT-Lym subscale score at cycle 3 is considered as mid-treatment score. If FACT-Lym subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score." (NCT01216683)
Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 47.9 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 46.8 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 46.5 |
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Baseline
The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at baseline
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 39.9 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 38.7 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 38.8 |
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Mid-induction Treatment
The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life. (NCT01216683)
Timeframe: Assessed at cycle 3, approximately 3 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 40.0 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 38.6 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 39.1 |
5-year Overall Survival Rate
"Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.~The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis." (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | proportion of participants (Number) |
|---|
| FLIPI 0-2/Unknown | 0.90 |
| FLIPI 3-5 | 0.81 |
5-year Overall Survival Rate
"Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.~The 5-year overall survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (<10 vs. >=10). Higher CIRS scores indicate higher severity with max score of 56 points." (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | proportion of participants (Number) |
|---|
| CIRS <10 | 0.87 |
| CIRS >=10 | 0.80 |
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Mid-treatment
"The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.~FACT-G total score at cycle 3 is considered as mid-treatment score. If FACT-G total score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score." (NCT01216683)
Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
| Intervention | score on a scale (Mean) |
|---|
| Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) | 85.5 |
| Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) | 84.2 |
| Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) | 85.2 |
3-year Progression-free Survival Rate
"Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.~Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.~The 3-year progression-free survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (<10 vs. >=10). Higher CIRS scores indicate higher severity with max score of 56 points." (NCT01216683)
Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
| Intervention | proportion of participants (Number) |
|---|
| CIRS <10 | 0.83 |
| CIRS >=10 | 0.68 |
Phase 2: 1 Year Survival Rate
1-year survival rate is defined as the percentage of participants still alive at year after the first dose of stud drug. (NCT01217957)
Timeframe: 1 year after first dose of study drug
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 92 |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 92 |
Phase 2: Duration of Response (DOR)
DOR was measured as the time in months from the date of first documentation of a confirmed response (CR + PR+ VGPR) to the date of the first documented disease progression (PD). Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Up to 787 days
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | NA |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | NA |
Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone
ORR was defined as the percentage of participants with Complete (CR) + Very Good Partial Response (VGPR) assessed by the investigatory using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or; 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 59 |
| Phase 2: Ixazomib 4.0mg/2.23 + Lenalidomide + Dexamethasone | 62 |
Phase 2: Overall Response Rate (ORR)
ORR was defined as the percentage of participants with CR, VGPR and Partial Response (PR) assessed by the investigator using IMWG criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: Up to 787 days
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 88 |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 88 |
Phase 2: Overall Survival (OS)
OS was measured as the time in months from the first dose of study treatment to the date of death + 1 day. (NCT01217957)
Timeframe: From the first dose of study treatment to the date of death (up to 787 days)
| Intervention | participants (Median) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | NA |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | NA |
Phase 2: Progression Free Survival (PFS)
PFS was measured as the time in months from the first dose of study treatment to the date of the first documented PD or death. (NCT01217957)
Timeframe: Up to 787 days
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 14.98 |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | NA |
Phase 2: Time to Best Response
Time to Best Response was measured as the time in months from the first dose of study treatment to the date of first documented documentation of a confirmed response of partial response (PR) or better. (NCT01217957)
Timeframe: Up to 787 days
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 2.96 |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 3.01 |
Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone
MTD of ixazomib will be determined by assessing adverse events and serious adverse events, clinical laboratory values, neurotoxicity grading, and vital sign measurements. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1: Ixazomib + Lenalidomide + Dexamethasone | 2.97 |
Phase 1: Rac: Accumulation Ratio of Ixazomib
The accumulation ratio (Rac) was estimated as the ratio of AUC(0-168) on Day 15 to the AUC(0-168) on Day 1. AUC(0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose for ixazomib. (NCT01217957)
Timeframe: Cycle 1, Day 15
| Intervention | Ratio (Geometric Mean) |
|---|
| Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | NA |
| Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | 1.849 |
| Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | 2.051 |
Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
Tmax: Time to reach the first maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax, obtained directly from the plasma concentration-time curve. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15
| Intervention | hours (Median) |
|---|
| Day 1 (n=1, 3, 4, 1) | Day 15 (n=2, 3, 4, 1) |
|---|
| Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | 1.020 | 4.165 |
,| Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | 1.520 | 1.000 |
,| Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | 1.060 | 1.015 |
,| Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | 0.250 | 2.000 |
Phase 2: Time to Progression (TTP)
TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD). (NCT01217957)
Timeframe: From the first dose of study treatment to the date of first documented progressive disease (Up to 787 days)
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | NA |
| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | NA |
Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
AUC(0-168) is a measure of the area under the plasma concentration-time curve from time 0 to 168 hours postdose for Ixazomib. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Day 1 (n=1, 3, 4, 1) | Day 15 (n=2, 3, 3, 1) |
|---|
| Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | NA | 834.608 |
,| Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | 587.667 | 1083.998 |
,| Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | 923.484 | 1831.324 |
,| Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | NA | NA |
Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Cmax: Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of ixazomib obtained directly from the plasma concentration-time curve. (NCT01217957)
Timeframe: Cycle 1, Days 1 and 15
| Intervention | ng/mL (Geometric Mean) |
|---|
| Day 1 (n=1, 3, 4, 1) | Day 15 (n=2, 3, 4, 1) |
|---|
| Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | NA | 11.999 |
,| Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | 22.303 | 31.368 |
,| Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | 94.779 | 53.517 |
,| Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | NA | NA |
Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
| Intervention | participants (Number) |
|---|
| Any AE | SAE |
|---|
| Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone | 3 | 2 |
,| Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone | 3 | 3 |
,| Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone | 6 | 1 |
,| Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone | 3 | 2 |
Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR)
Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT01217957)
Timeframe: After Cycles 3, 6 and 9 (Up to 787 days)
| Intervention | percentage of participants (Number) |
|---|
| After 3 cycles | After 6 cycles | After 9 cycles |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 35 | 47 | 57 |
,| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 37 | 48 | 58 |
Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR)
Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. CR=Negative immunofixation on the serum and urine + Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR= CR + Normal free light chain (FLC) ratio and Absence of clonal cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to < 200 mg per 24 hours. VGPR= Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. nCR=Positive immunofixation analysis of serum or urine as the only evidence of disease. Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. MR=25% to 49% reduction in serum paraprotein and 50% to 89% reduction in urine light chain excretion for 6 weeks. (NCT01217957)
Timeframe: Cycles 3, 6, 9 and 12 (Up to 787 days)
| Intervention | percentage of participants (Number) |
|---|
| CR | sCR | VGPR | nCR | PR | MR |
|---|
| Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 20 | 6 | 39 | 2 | 67 | 6 |
,| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 23 | 10 | 38 | 2 | 65 | 6 |
Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 787 days)
| Intervention | percentage of participants (Number) |
|---|
| Grade 3 or Higher AEs | SAEs | AEs Resulting in Treatment Discontinuation |
|---|
| Phase 2 :Ixazomib 4.0 mg + Lenalidomide + Dexamethasone | 76 | 40 | 8 |
,| Phase 2: Ixazomib 4.0 mg/2.23 + Lenalidomide + Dexamethasone | 75 | 43 | 8 |
Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone
RP2D will be determined based on number and type of adverse event and serious adverse events, assessments of clinical laboratory values, neurotoxicity grading, and treatment discontinuation. (NCT01217957)
Timeframe: Until occurrence of progressive disease or unacceptable toxicity (Up to 336 days)
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1: Ixazomib + Lenalidomide + Dexamethasone | 2.23 |
Number of Patients With a Transfusion Independence Response
Response defined as transfusion independence (no red blood cell transfusions) for at least 8 weeks, anytime during the six 28-day cycles of therapy. (NCT01222195)
Timeframe: Over six 28-day cycles (approximately 168 days)
| Intervention | participants (Number) |
|---|
| Lenalidomide + Darbepoetin Alfa | 0 |
Objective Response Rate (ORR)
Objective response rate (ORR) defined as the percentage of participants with a best response on-study of partial response (PR) or better (stringent CR [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]) based on the Independent Review Committee (IRC) assessment of best response using the European Group for Blood and Bone Marrow Transplant (EBMT) assessment criteria. Participants were censored at the last adequate assessment prior to the start of any subsequent systemic-therapy or at the last adequate assessment prior to 2 missing assessments (> 10 weeks). Participants who died more than 10 weeks after the randomization date and had no on-treatment assessment were censored at the randomization date. Clinical deterioration was not considered progression. Assessments were made every 4 weeks. (NCT01239797)
Timeframe: From randomization up to approximately 38 months
| Intervention | Percentage of participants (Number) |
|---|
| Lenalidomide + Dexamethasone + Elotuzumab | 78.5 |
| Lenalidomide + Dexamethasone | 65.5 |
Change From Baseline of Mean Score Pain Severity (BPI-SF)
"The change from baseline of the mean score of pain severity at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale." (NCT01239797)
Timeframe: From baseline up to approximately 38 months
| Intervention | Score on a scale (Mean) |
|---|
| Lenalidomide + Dexamethasone + Elotuzumab | 0.52 |
| Lenalidomide + Dexamethasone | -0.04 |
Change From Baseline of Mean Score Pain Interference (BPI-SF)
"The change from baseline of the mean score of pain interference at the end of treatment using the Brief Pain Inventory-Short Form (BPI-SF). The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 0 (No pain, No interference) to 10 (Pain as bad as you can imagine, Highest imaginable interference) numeric rating scale." (NCT01239797)
Timeframe: From baseline up to approximately 38 months
| Intervention | Score on a scale (Mean) |
|---|
| Lenalidomide + Dexamethasone + Elotuzumab | 0.95 |
| Lenalidomide + Dexamethasone | 0.48 |
Stage II - Overall Response Rate
Rate of overall response by incidence of Complete Response, Partial Response, and Stable Disease per Modified International Working Group (IWG) response criteria for patients enrolled in Stage II (NCT01241734)
Timeframe: After 2 Cycles of Treatment (28 Day Cycles)
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 2 |
Stage I - Dose Limiting Toxicity Incidence Rate
Incidence of DLT in patients enrolled in stage I for determination of MTD (NCT01241734)
Timeframe: Cycle 1 of Treatment (28 Days)
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 0 |
Stage I - Safety (Type, Frequency, Severity and Relationship of Adverse Events to Study Treatment) and Tolerability
Determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with rituximab, Ifosfamide, etoposide, and carboplatin (RICE) for the treatment of DLBCL patients in first relapse by incidence of dose-limiting toxicity (DLT) for Stage I Patients Only (NCT01241734)
Timeframe: Cycle 1 of Treatment (28 Days)
| Intervention | mg (Number) |
|---|
| Revlimid (Lenalidomide) in Combination | 25 |
Stage II - 1 Year Overall Survival (OS)
1 Year Overall Survival (OS) of patients enrolled in stage II (NCT01241734)
Timeframe: Up to 1 Year
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 2 |
Stage II - 1 Year Progression Free Survival (PFS)
Rate of Progression Free Survival (PFS) at 1 Year of patients enrolled in stage II (NCT01241734)
Timeframe: Up to 1 Year
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 2 |
Stage II - 2 Year Overall Survival (OS)
2 Year Overall Survival (OS) of patients enrolled in stage II (NCT01241734)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 2 |
Stage II - 2 Year Progression Free Survival (PFS)
Rate of Progression Free Survival (PFS) at 1 Year of patients enrolled in stage II (NCT01241734)
Timeframe: Up to 2 Years
| Intervention | Participants (Count of Participants) |
|---|
| Stage I, Cohort 1 | 0 |
| Stage I, Cohort 2 | 0 |
| Stage I, Cohort 3 | 0 |
| Stage I, Cohort 4 | 0 |
| Stage II | 2 |
The Overall Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine
(NCT01241786)
Timeframe: 9 Months
| Intervention | participants (Number) |
|---|
| Revlamid + Vidaza | 5 |
the Rate of Response to the Combination of Azacitidine + Lenalidomide in Select Patients
the rate of response to the combination of azacitidine + lenalidomide in select patients with relapsed/refractory CLL and small lymphocytic lymphoma (SLL). (NCT01241786)
Timeframe: 9 Months
| Intervention | participants (Number) |
|---|
| Study Terminated | 0 |
The Progression Free Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine
(NCT01241786)
Timeframe: 9 Months
| Intervention | Months (Median) |
|---|
| Revlamid + Vidaza | 1 |
Duration of Reduction in Spleen Volume
Duration of spleen volume reduction is defined as the time from the first occurrence of a >=35% reduction from baseline in spleen volume until the date of the first documented progression. (NCT01243944)
Timeframe: 256 Weeks
| Intervention | probability (Number) |
|---|
| 16 weeks | 32 weeks | 48 weeks | 64 weeks | 80 weeks | 96 weeks | 112 weeks | 128 weeks | 144 weeks | 160 weeks | 176 weeks | 192 weeks | 208 weeks | 224 weeks | 240 weeks | 256 weeks |
|---|
| Ruxolitinib | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 0.98 | 0.95 | 0.95 | 0.95 | 0.93 | 0.93 | 0.93 | 0.87 | 0.72 | NA | NA |
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
Durable Spleen Volume Reduction was defined as a participant who achieved at least 35% reduction from baseline in spleen volume at Week 32 and maintained that response 48 weeks after randomization. (NCT01243944)
Timeframe: 48 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 37.3 |
| Best Available Therapy | 0.9 |
The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
Durable Complete or Partial Clinicohematologic Response was defined as any participant who achieved complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera at Week 32 and maintained that response 48 weeks after randomization. (NCT01243944)
Timeframe: 48 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Complete response rate | Partial response rate |
|---|
| Best Available Therapy | 0.9 | 0.9 |
,| Ruxolitinib | 7.3 | 50.9 |
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
Durable Hematocrit Control was defined as any participant who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization. (NCT01243944)
Timeframe: 48 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 54.5 |
| Best Available Therapy | 1.8 |
The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
Durable Complete Hematological Remission was defined as any participant who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization. (NCT01243944)
Timeframe: 48 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 20.9 |
| Best Available Therapy | 0.9 |
The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
Overall Clinicohematologic Response is defined as any participant who achieved a complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera (PV). A Complete Response (CR) is defined as: hematocrit control, spleen volume reduction at least 35% from baseline, platelet count less than or equal to 400 x 10(9)/L, and white blood cell count less than or equal to 10 x 10(9)/L. A Partial Response (PR) is defined as hematocrit control or response in all 3 of the other criteria. (NCT01243944)
Timeframe: 32 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Complete response rate | Partial response rate |
|---|
| Best Available Therapy | 0.9 | 18.8 |
,| Ruxolitinib | 8.2 | 54.5 |
Estimated Duration of the Primary Response
"Duration of the primary response is defined as the time from the first occurrence when both components of the primary endpoint are met until the date of the first documented disease progression (end of response).~Kaplan-Meier estimates are provided for duration of primary response." (NCT01243944)
Timeframe: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
| Intervention | probability (Number) |
|---|
| 16 weeks | 32 weeks | 48 weeks | 64 weeks | 80 weeks | 96 weeks | 112 weeks | 128 weeks | 144 weeks | 160 weeks | 176 weeks | 192 weeks | 208 weeks | 224 weeks | 240 weeks | 256 weeks |
|---|
| Ruxolitinib | 1.00 | 1.00 | 0.92 | 0.92 | 0.92 | 0.88 | 0.84 | 0.84 | 0.84 | 0.79 | 0.79 | 0.74 | 0.74 | 0.74 | NA | NA |
Duration of the Absence of Phlebotomy Eligibility
Duration of the absence of phlebotomy eligibility is defined as the time from the first occurrence of absence of phlebotomy eligibility until the date of the first documented progression. (NCT01243944)
Timeframe: 256 Weeks
| Intervention | probability (Number) |
|---|
| 16 weeks | 32 weeks | 48 weeks | 64 weeks | 80 weeks | 96 weeks | 112 weeks | 128 weeks | 144 weeks | 160 weeks | 176 weeks | 192 weeks | 208 weeks | 224 weeks | 240 weeks | 256 weeks |
|---|
| Ruxolitinib | 1.00 | 1.00 | 0.97 | 0.92 | 0.91 | 0.91 | 0.87 | 0.84 | 0.84 | 0.82 | 0.79 | 0.77 | 0.73 | 0.73 | 0.73 | 0.73 |
Estimated Duration of the Complete Hematological Remission
"Duration of the complete hematological remission is defined as the time from the first occurrence of complete hematological remission until the date of the first documented progression (end of response).~Kaplan-Meier estimates are provided for duration of complete hematological remission." (NCT01243944)
Timeframe: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
| Intervention | probability (Number) |
|---|
| 16 weeks | 32 weeks | 48 weeks | 64 weeks | 80 weeks | 96 weeks | 112 weeks | 128 weeks | 144 weeks | 160 weeks | 176 weeks | 192 weeks | 208 weeks | 224 weeks | 240 weeks | 256 weeks |
|---|
| Ruxolitinib | 1.00 | 1.00 | 0.88 | 0.83 | 0.74 | 0.74 | 0.69 | 0.69 | 0.65 | 0.65 | 0.55 | 0.55 | 0.55 | 0.55 | NA | NA |
Duration of The Overall Clinicohematologic Response
Duration of the overall clinicohematologic response was defined as the time from the first occurrence of complete response (CR) or partial response (PR) until the date of the first documented disease progression. (NCT01243944)
Timeframe: 256 Weeks
| Intervention | probability (Number) |
|---|
| 16 weeks | 32 weeks | 48 weeks | 64 weeks | 80 weeks | 96 weeks | 112 weeks | 128 weeks | 144 weeks | 160 weeks | 176 weeks | 192 weeks | 208 weeks | 224 weeks | 240 weeks | 256 weeks |
|---|
| Ruxolitinib | 1.00 | 0.99 | 0.96 | 0.91 | 0.88 | 0.88 | 0.85 | 0.82 | 0.82 | 0.80 | 0.75 | 0.70 | 0.67 | 0.67 | 0.67 | 0.67 |
The Percentage of Participants Achieving Complete Hematological Remission at Week 32
Complete Hematological Remission at Week 32 was defined as any participant who achieved hematocrit control with a platelet count less than or equal to 400 X 10^9/L and a white blood cell count less than or equal to 10 X 10^9/L. (NCT01243944)
Timeframe: 32 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 23.6 |
| Best Available Therapy | 8.0 |
The Percentage of Participants Achieving a Primary Response at Week 32
Primary response was defined as having achieved hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and Spleen Volume Reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32). (NCT01243944)
Timeframe: 32 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 22.7 |
| Best Available Therapy | 0.9 |
The Percentage of Participants Achieving a Durable Primary Response at Week 48
Durable Primary Response was defined as any participant who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization. (NCT01243944)
Timeframe: 48 Weeks
| Intervention | percentage of participants (Number) |
|---|
| Ruxolitinib | 20.0 |
| Best Available Therapy | 0.9 |
Time to Discontinuation of Treatment
(NCT01246076)
Timeframe: Up to 56 weeks (14 cycles)
| Intervention | cycles (Median) |
|---|
| Lenalidomide | 2 |
Number of Participants With Confirmed Responses (Complete Remission, Partial Remission, or Hematologic Improvement) as Defined by the International Working Group Criteria
"Complete remission (CR): ≤5% myeloblasts bone marrow blasts, normal maturation in all cell lines (dysplasia will be noted), ≥11 g/dl peripheral blood hemoglobin, ≥100x10^9cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood absolute neutrophil count (ANC), and 0% peripheral blood blasts.~Marrow complete remission (MCR): ≤5% myeloblasts and decreased by ≥50% compared to pre-treatment bone marrow blasts, bone marrow morphology not relevant, and peripheral blood (if hematological improvement they will be noted in addition to marrow CR).~Partial remission (PR): previously had ≥5% myeloblasts and now have ≥5% myeloblasts but decreased by ≥50% compared to pre-treatment, bone marrow morphology not relevant, ≥11 g/dl peripheral blood hemoglobin, ≥100x109cells/μL peripheral blood platelets, ≥1000 cells/ μL peripheral blood ANC, and 0% peripheral blood blasts" (NCT01246076)
Timeframe: Up to 56 weeks (14 cycles of treatment)
| Intervention | participants (Number) |
|---|
| CR | MCR | PR | HI |
|---|
| Lenalidomide | 0 | 8 | 0 | 2 |
Duration of Response
(NCT01246076)
Timeframe: Until 6 months after end of treatment
| Intervention | days (Median) |
|---|
| Lenalidomide | 70 |
Overall Survival Rate
-Overall survival rate is the percentage of participants who were alive 6 months after end of treatment. (NCT01246076)
Timeframe: 6 months after end of treatment (up to 82 weeks from start of treatment)
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 29 |
Phase I: Number of Participants With Dose Limiting Toxicity
The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sirolimus, tacrolimus and lenalidomid. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level. (NCT01303965)
Timeframe: 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Dose Finding | 0 |
Phase II - Time to Platelet Engraftment
Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided. (NCT01303965)
Timeframe: Transplant (Day 0) through 1 year post-transplant
| Intervention | days (Median) |
|---|
| Phase II | 19 |
Phase II - Time to Neutrophil Engraftment
Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided. (NCT01303965)
Timeframe: Transplant (Day 0) through 1 year post transplant
| Intervention | days (Median) |
|---|
| Phase II | 11 |
Phase II - Percent of Patients With Acute Graft Versus Host Disease (GvHD)
"Percent of patients and the 95% Binomial Confidence interval who had any stage I-IV acute GvHD based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms for patients in Phase II. Zero means no acute GvHD was reported, and higher stages are worse outcomes (range of 0-4).~For skin: 0=no rash; 1=erthematous macular rash over <25% body surface; 2=over 25-50% of body surface; 4=bullae, exfoliation ulcerative dermatitis.~For liver (bilirubin (mg/dL)): 0= <2.0; 1= 2-<2.9; 3= 3-<5.9; 4= >=15 . For gut changes (diarrhea[ml/day]): 0=none; 1= >500-1000; 2= >1000-1500; 3= >1500; 4=severe abdominal pain with or without ileus.~Overall grade 0: Skin=0; liver=0; gut changes=0. Overall grade 1: Skin with 1 or 2; liver=0; gut changes=0. Overall grade 2: Skin with 1, 2, or 3; liver=1; gut changes=1. Overall grade 3: Skin with 2 or 3; liver with 2 or 3; gut changes with 2 or 3. Overall grade 4: Patients with grade 4 toxicity in any organ system." (NCT01303965)
Timeframe: Day 0 through 1 year post transplantation
| Intervention | percentage of participants (Number) |
|---|
| Phase II | 36.4 |
Phase II - Percent of Patients With Chronic Graft Versus Host Disease (GvHD)
Percent of patients and the 95% Binomial Confidence interval who had any chronic GvHD reported based on Filipovich et al. consensus document (BB&MT 2005) and Akpek et al. chronic GvHD grading system (Blood 2003) for patients in Phase II. (NCT01303965)
Timeframe: Transplant (Day 0) through 1 year post-transplant
| Intervention | percentage of participants (Number) |
|---|
| Phase II | 18.2 |
Phase II: Percent of Patients Alive and Free of Progression at 12 Months Following Transplant
Percent of patients and the 95% Binomial Confidence interval who were alive and free of progression at 12 months following transplant for the patients in Phase II. Progression will be based on International Myeloma Working Group criteria where patients may meet any one of the following criteria - increase of 25% or more in serum or urine M-protein from baseline, Serum M-protein and/or the absolute increase must be >=0.5 g/dl, Urine M-protein and/or absolute increase must be >=200 mg/24 hours, development of new bone lesions or soft tissue plasmacyomas or definite increase in the size of existing bone lesions or soft tissue plasmacyomas, or development of hypercalcemia (corrected serum Ca++>11.5 mg/dl) that can be attributed solely to plasma cell proliferative disease. (NCT01303965)
Timeframe: Transplant (Day 0) through 1 year post-transplant
| Intervention | percentage of participants (Number) |
|---|
| Phase II | 18.2 |
Progression Free Survival (PFS) Rate at Specific Time-points
PFS rate is defined as the percentage of participants experiencing PFS at the defined time-points. (NCT01335399)
Timeframe: From randomization to the specified time-point (up to 5 years)
| Intervention | Percent of participants (Number) |
|---|
| 1 year | 2 year | 3 year | 4 year | 5 year |
|---|
| E-Ld Cohort | 0.77 | 0.59 | 0.46 | 0.36 | 0.26 |
,| Ld Cohort | 0.76 | 0.55 | 0.41 | 0.33 | 0.25 |
Mean Change From Baseline of Pain Severity Score and Pain Interference Score
"Pain severity (sensory dimension) and pain interference (reactive dimension, assessing the degree to which pain interferes with function) are measured using the Brief Pain Inventory- Short Form (BPI-SF).~BPI-SF numeric rating scale goes from 0 (No pain) to 10 (Pain as bad as you can imagine)." (NCT01335399)
Timeframe: From Baseline to End of Treatment (approximately 8 years)
| Intervention | Rating score (Mean) |
|---|
| Pain Severity | Pain Interference |
|---|
| E-Ld Cohort | 0.02 | 0.33 |
,| Ld Cohort | -0.25 | -0.18 |
Progression-Free Survival (PFS)
"PFS is defined as the time from randomization to the date of the first documented tumor progression (as determined by the Independent Review Committee (IRC)) or death due to any cause.~The IRC conducted a blinded, independent review of the tumor assessments based on the European Group for Blood and Bone Marrow Transplant (EBMT) criteria.~Censoring rules applied:~Participants receiving subsequent systemic anti-myeloma therapy prior to documented progression were censored at the date of the last adequate tumor assessment prior to new therapy.~Participants who had an event (progression or death) > 10 weeks after their last tumor assessment were censored at their last adequate tumor assessment prior to the event.~Participants without progression or death (and not receiving subsequent therapy prior to progression) were censored at their last adequate tumor assessment.~Participants without any post-baseline tumor assessments were censored on the date of randomization" (NCT01335399)
Timeframe: From randomization to date of first documented tumor progression or death due to any cause (up to 8 years)
| Intervention | Months (Median) |
|---|
| E-Ld Cohort | 31.38 |
| Ld Cohort | 29.47 |
Overall Survival (OS)
"Survival is defined as the time from randomization to the date of death. A participant who did not die had his or her survival duration censored at the date of last contact ('last known date alive)." (NCT01335399)
Timeframe: From randomization to the date of death (up to 8 years)
| Intervention | Months (Median) |
|---|
| E-Ld Cohort | 60.42 |
| Ld Cohort | 57.56 |
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with objective response among all randomized subjects. Participants with an objective response are those participants experiencing a partial response (PR) or better, based on Independent Review Committee (IRC) assessment, as per EBMT criteria. (NCT01335399)
Timeframe: From randomization to primary completion date (approximately 8 years)
| Intervention | Percent of Participants (Number) |
|---|
| E-Ld Cohort | 82.9 |
| Ld Cohort | 79.4 |
Maximum Tolerated Dose (MTD) of Lenalidomide
MTD was determined by testing planned increasing doses up to 25 mg daily dose on days 1-14, starting at 10mg. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in > 33% of participants. DLTs were defined as any lenalidomide-related Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) Grade 3 or 4 adverse events (NCT01342172)
Timeframe: after 1 cycle (each cycle is 21 days)
| Intervention | mg (Number) |
|---|
| Lenalidomide | 10 |
Best Overall Response
"Best Overall Response to evaluate lenalidomide as maintenance treatment in patients achieving an objective response of either complete response or partial response following completion of 6 cycles of combination therapy.~Complete Response (CR) - CR of target lesions and no new lesions Partial Response (PR) -PR of target lesions and no new lesions Stable Disease (SD) - SD of target lesions and no new lesions Progression Disease (PD) - any status of target lesions and new lesions" (NCT01342172)
Timeframe: 168 days
| Intervention | Participants (Count of Participants) |
|---|
| CR | PR |
|---|
| Lenalidomide | 1 | 2 |
Number of Grade >=3 Adverse Events
Number of grade >=3 adverse events to assess the safety of combination therapy with gemcitabine, cisplatin plus lenalidomide as determined by the frequency and severity of adverse events as per the NCI Common Terminology for Adverse Events (CTCAE) version 4.0. (NCT01342172)
Timeframe: Day 1 and Day 8 of each treatment cycle; 21 days after the last dose of Lenalidomide
| Intervention | events (Number) |
|---|
| Grade 3 | Grade 4 |
|---|
| Lenalidomide | 28 | 7 |
The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide
"The objective response rate as determined by Response Evaluation Criteria in Solid Tumors (RECIST).~Complete Response (CR) Disappearance of all target lesions for a period of at least one month.~Partial Response (PR) At least a 30% decrease in the sum of the longest diameter of measures lesions (target lesions), taking as reference the baseline sum of the longest diameter.~Stable Disease (NR/SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started.~Progressive Disease (PD) A 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions), taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions" (NCT01342172)
Timeframe: After 2 cycles (a cycle is 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| CR | PR | SD | PD | not evaluable |
|---|
| Lenalidomide | 1 | 2 | 3 | 2 | 1 |
Maximum Tolerated Dose of CEP-18770
MTD was based on the assessment of dose-limiting toxicity (DLT) during cycle 1 only and was defined as the highest dose at which fewer than one-third of participants in a cohort experience DLT. A DLT was defined as any of the following drug-related toxicities occurring during Cycle 1: Hematologic adverse events (AEs) (Grade 4 hematologic AEs, Grade 3 hematologic AEs with sequelae); Grade 3 nonhematologic AEs; Neuropathy (Grade 2 neuropathy, Grade 1 neuropathy with pain, worsening grade of neuropathy or new symptoms of pain associated with neuropathy); Any other toxicity that, in the judgment of the principal investigator, was a DLT; If a participant cannot receive 75% of the planned dose for any of the 3 agents (missing >1 dose of CEP-18770, or >5 doses of lenalidomide, or >1 dose of dexamethasone [either consecutively or separately]), due to a drug-related AE, the event was considered a DLT, even if the grade of toxicity was lower than specified DLT determination as described above. (NCT01348919)
Timeframe: Cycle 1 (28 days)
| Intervention | mg/m^2 (Number) |
|---|
| Overall Population | 1.8 |
Duration of Response (DOR) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria
DOR was defined as the time interval from the date of first response (sCR, CR, VGPR, or PR) to the date of disease progression. sCR, CR, VGPR, and PR as defined in outcome measure 1. Disease progression was defined as any 1 or more of the following: Increase of 25% or more from lowest response level in any 1 or more of the following: - serum M-component (absolute increase must be ≥0.5 grams [g]/deciliter [dL]), - urine M-component (absolute increase must be ≥200 mg/24 hours), bone marrow plasma cell percentage ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; and development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that could be attributed solely to the plasma cell proliferation disorder. (NCT01348919)
Timeframe: From the date of first response to the date of disease progression (up to approximately 1.5 years)
| Intervention | months (Median) |
|---|
| CEP-18770 Dose B | NA |
Overall Response Rate (ORR) in Participants Treated at the (Maximum Tolerated Dose) MTD, as Assessed Using International Myeloma Working Group (IMWG) Criteria
The ORR is defined as percentage of participants who achieve a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) during the study. sCR: negative immunofixation in serum and urine; disappearance of any soft tissue plasmacytomas; < 5% plasma cells in bone marrow; normal free light chain (FLC) ratio; and absence of clonal cells in bone marrow. CR: negative immunofixation in serum and urine; disappearance of any soft tissue plasmacytomas; and <5% plasma cells in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis; 90% or greater reduction in serum M-protein level and urine M-protein level less than 100 milligrams (mg)/24 hours. PR: ≥50% reduction in serum M-protein level; ≥90% reduction in 24-hour urinary M-protein level or reduction to less than 200 mg per 24 hours; and ≥50% reduction in the size of any soft tissue plasmacytomas present at baseline. (NCT01348919)
Timeframe: From the first administration of CEP-18770 up to approximately 1.5 years
| Intervention | percentage of participants (Number) |
|---|
| CEP-18770 Dose B | 40 |
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. (NCT01348919)
Timeframe: From the first administration of CEP-18770 up to approximately 1.5 years
| Intervention | Participants (Count of Participants) |
|---|
| CEP-18770 Dose A | 3 |
| CEP-18770 Dose B | 5 |
| CEP-18770 Dose C | 3 |
Time to Reach Cmax (Tmax) of CEP-18770
(NCT01348919)
Timeframe: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
| Intervention | hours (Median) |
|---|
| Day 1 | Day 15 |
|---|
| CEP-18770 Dose A | 0.07 | 0.07 |
,| CEP-18770 Dose B | 0.08 | 0.08 |
,| CEP-18770 Dose C | 0.10 | 0.08 |
Maximum Observed Plasma Concentration (Cmax) of CEP-18770
(NCT01348919)
Timeframe: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
| Intervention | nanograms (ng)/ milliliter (mL) (Mean) |
|---|
| Day 1 | Day 15 |
|---|
| CEP-18770 Dose A | 579.49 | 639.59 |
,| CEP-18770 Dose B | 663.00 | 628.07 |
,| CEP-18770 Dose C | 876.97 | 977.09 |
Area Under the Plasma Concentration-Time Curve From Time 0 to t (AUC0-t) of CEP-18770
(NCT01348919)
Timeframe: Before and immediately after end of infusion (EOI) and at approximately 2, 4, and 8 hours after the EOI on Days 1 and 15 of Cycle 1
| Intervention | ng*hours/mL (Mean) |
|---|
| Day 1 | Day 15 |
|---|
| CEP-18770 Dose A | 673 | 1595 |
,| CEP-18770 Dose B | 1371 | 2071 |
,| CEP-18770 Dose C | 1527 | 2266 |
Time to Progression (TTP) for Participants Treated With CEP-18770 at the MTD, as Assessed Using IMWG Criteria
TTP was defined as the time interval from the date of first dose to the date of disease progression. Disease progression was defined as any 1 or more of the following: Increase of 25% or more from lowest response level in any 1 or more of the following: - serum M-component (absolute increase must be ≥0.5 g/dL), - urine M-component (absolute increase must be ≥200 mg/24 hours), bone marrow plasma cell percentage ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; and development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that could be attributed solely to the plasma cell proliferation disorder. (NCT01348919)
Timeframe: From the date of first dose of study drug to the date of disease progression (up to approximately 1.5 years)
| Intervention | months (Median) |
|---|
| CEP-18770 Dose B | NA |
Grade 3-4 Toxicity
Number of participants who experienced grade 3-4 toxicity as per CTCAE 4.0. (NCT01349569)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | 0 |
Response Conversion Rate
Number of participants who converted from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, < 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells. (NCT01349569)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | 8 |
Time to Response
"Median time for conversion of response from near complete remission (nCR) to complete remission (CR) as measured by the International Myeloma Working Group Uniform Response Criteria. Near complete remission is defined as negative serum and urine electrophoresis, < 5% plasma cells in the bone marrow, and positive serum and/or urine immunofixation. Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.~as measured by immunofixation converting from positive to negative." (NCT01349569)
Timeframe: Up to 4 years
| Intervention | months (Median) |
|---|
| Myeloma Vaccine, Prevnar-13 Vaccine, & Lenalidomide | 11.7 |
Tumor-specific Immunity as Assessed by Percentage of CD3+/CSFSE-low/IFN-gamma+ Cells
Immunity is measured by the percentage of CD3+/CSFSE-low/IFN-gamma+ cells. A positive result for a given participant is defined as greater than two standard deviations above that participant's baseline. The data are presented as three groups because the responses were analyzed separately, but all participants were part of the single study arm as represented by the remainder of the record. GVAX-specific immune response and Prevnar-specific immune response was assessed in the same patient by using GVAX and Prevnar-specific co-markers. (NCT01349569)
Timeframe: Baseline, Cycle 3 Day 14, end of study (up to 1 year)
| Intervention | percentage of cells (Mean) |
|---|
| Complete Response (CR) patients at Baseline | CR patients at Cycle 3 Day 14 | CR patients at end of Study | Progressive Disease (PD) patients at Baseline | PD patients at Cycle 3 Day 14 | PD patients at end of study |
|---|
| GVAX Vaccine | 0.36 | 13.3 | 13.7 | 0.45 | 5.7 | 0.21 |
,| Pre-vaccine (Baseline) | 1.2 | 7.3 | 6.3 | 0.43 | 1.7 | 0.4 |
,| Prevnar Vaccine | 0 | 4.54 | 3.6 | 0 | 0 | 1.7 |
Time-to-next Treatment
(NCT01355705)
Timeframe: 9 months
| Intervention | days (Median) |
|---|
| Amrubicin + Lenalidomide + Dexamethasone | 92 |
Duration of Response (DOR)
(NCT01355705)
Timeframe: 140 days
| Intervention | days (Median) |
|---|
| Amrubicin + Lenalidomide + Dexamethasone | 133 |
Progression-free Survival (PFS)
"Progression-free survival (PFS) is alive and free from progression, per the modified International Myeloma Working Group Uniform Response Criteria, defined as any of:~Serum monoclonal protein ≥ 125% baseline and/or ≥ +0.5 g/dL from baseline,~Urine monoclonal protein ≥ 125% baseline and/or ≥ +200 mg/24 hour from baseline~New or increased bone lesions or plasmacytomas~Serum calcium > 11.5 mg/dL (attributed to increased plasma cells)" (NCT01355705)
Timeframe: 9 months
| Intervention | days (Median) |
|---|
| Amrubicin + Lenalidomide + Dexamethasone | 96 |
Percentage of Participants Alive at One Year
Defined as the percentage of participants who survived at one year (NCT01358734)
Timeframe: Up to 12 months
| Intervention | Percentage of participants (Number) |
|---|
| Lenalidomide | 21.4 |
| Azacitidine Plus Lenalidomide | 43.9 |
| Azacitidine | 52.3 |
Kaplan Meier Estimates for One Year Survival
One-year survival rate was defined as all deaths within one year from the date of randomization. All others censored at the at year 1 or date of discontinuation (NCT01358734)
Timeframe: Up to 24 months
| Intervention | months (Median) |
|---|
| Lenalidomide | 3.00 |
| Azacitidine Plus Lenalidomide | 9.61 |
| Azacitidine | 13.67 |
Number of Participants With a Second Primary Malignancy
Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in. (NCT01358734)
Timeframe: From randomization of the last participant up to a minimum of 4 years following discontinuation
| Intervention | Participants (Number) |
|---|
| Lenalidomide | 0 |
| Azacitidine Plus Lenalidomide | 0 |
| Azacitidine | 3 |
Overall Survival
Overall Survival reported at the end of the study are for those participants who were alive at the end of the study (NCT01358734)
Timeframe: From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)
| Intervention | months (Median) |
|---|
| Lenalidomide | 0.2 |
| Azacitidine Plus Lenalidomide | 7.1 |
| Azacitidine | 4.1 |
Number of Participants With Treatment Emergent Adverse Events (TEAE)
TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event. Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death (NCT01358734)
Timeframe: From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
| Intervention | participants (Number) |
|---|
| Any TEAE | ≥1 TEAE related to study drug | ≥1 TEAE CTCAE Grade 3 or 4 TEAE | ≥1 TEAE CTCAE Gr 3 or 4 TEAE related to study drug | ≥1 TEAE CTCAE Grade 5 | ≥1 Serious TEAE | ≥1 Serious TEAE related to study drug | ≥1TEAE leading to discontinuation of study drug | ≥1TEAE leading to dose reduction of study drug | ≥1TEAE leading to dose interruption of study drug |
|---|
| Azacitidine | 32 | 30 | 29 | 18 | 5 | 25 | 7 | 4 | 2 | 10 |
,| Azacitidine Plus Lenalidomide | 38 | 35 | 34 | 25 | 10 | 29 | 16 | 12 | 8 | 21 |
,| Lenalidomide | 14 | 13 | 14 | 11 | 5 | 13 | 10 | 6 | 0 | 8 |
Progression-free Survival (PFS)
(NCT01373229)
Timeframe: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first
| Intervention | months (Mean) |
|---|
| Lenalidomide + Plerixafor+ Rituximab | 11 |
Overall Survival (OS)
(NCT01373229)
Timeframe: the time from day 1 of treatment to death or 2 years, whichever comes first
| Intervention | months (Mean) |
|---|
| Lenalidomide + Plerixafor+ Rituximab | 5.5 |
Overall Response (Complete Response/Partial Response)
"NCI 96 Response Criteria~CR (Complete Response):~Lymphadenopathy = none > 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = <4000 per microliter Marrow = normocellular, <30% lymphocytes, no B-lymphoid nodules. Platelet count = >100,000 per microliter Hemoglobin = >11.0 grams per deciliter Neutrophils = >1500 per microliter~PR (Partial Response):~Lymphadenopathy = Decrease >/= 50% Hepatomegaly = Decrease >/= 50% Splenomegaly = Decrease >/= 50% Blood lymphocytes = Decrease >/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = >100,000 per microliter or increase >/= 50% over baseline Hemoglobin = >11.0 grams per deciliter or increase >/= 50% over baseline Neutrophils = >1500 per microliter or increase >/= 50% over baseline" (NCT01373229)
Timeframe: at the end of 4 months of combination treatment and at 2 months after completion of therapy
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide + Plerixafor+ Rituximab | 0 |
Maximum Tolerated Dose
(NCT01373229)
Timeframe: 4-16 months
| Intervention | mg/kg (Number) |
|---|
| Lenalidomide + Plerixafor+ Rituximab | 0.24 |
Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs or SAEs per category. SAEs will be specifically labeled as such. Participants were assessed at monthly intervals (corresponding to Revlimid™ refill points for adverse events), classified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and these were tabulated. (NCT01373294)
Timeframe: Duration of study treatment and follow-up - average of 12 months
| Intervention | participants (Number) |
|---|
| Hematuria | Urinary frequency | Urinary urgency | Urinary tract pain | Bladder spasm | Fatigue | Edema face | Edema limbs | Fever | Pain | Nausea | Erythroderma | Pruritus | Rash acneiform | Rash maculo-papular | Urinary tract infection | Pharyngitis | Platelet count decreased | SAE: Grade 3 Myocardial infarction | Headache | Peripheral sensory neuropathy |
|---|
| A: Combination Arm | 6 | 3 | 3 | 2 | 1 | 7 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 |
,| B: Control Arm | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Arm A: Progression Free Survival (PFS)
The 1-year progression free/ recurrence free/ bladder-intact survival was tabulated for the experimental arm for a median follow-up period of 369 days. The progression free/ recurrence free/ bladder-intact survival is defined as the time from start of study treatment to first documentation of objective tumor progression, recurrence, bladder resection or irradiation or to death due to any cause, whichever comes first. PFS data was not collected for participants in the Arm B: Control because too few participants were enrolled in Arm B to conduct the planned per Arm comparison (NCT01373294)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| A: Combination Arm | 8 |
Duration of Response
Median length of response in months. (NCT01374217)
Timeframe: Up to 6 months
| Intervention | months (Median) |
|---|
| Tadalafil | 2.3 |
Quality of Life Scores
Median change in symptom scores. Scale is the EORTC QLQ-C30. There are three domains: symptom scale (score range 7-14); past week (score range 21-82); and global health status (score range 2-14). Higher or increasing scores mean worse outcomes; lower or decreasing scores mean better outcomes. (NCT01374217)
Timeframe: 3 months (M3) and 6 months (M6)
| Intervention | change in score on a scale (Median) |
|---|
| Symptoms (M3) | Past week (M3) | Global health status (M3) | Symptoms (M6) | Past week (M6) | Global health status (M6) |
|---|
| Tadalafil | 0 | 5 | -1.5 | 1 | 6 | -1 |
Time to Progression
Median time to progression of disease in days. (NCT01374217)
Timeframe: Up to 71 days
| Intervention | days (Median) |
|---|
| Tadalafil | 48 |
Response Rate
Percentage of participants who responded to the addition of tadalafil. Response is defined as a complete remission (CR), very good partial remission (VGPR), partial remission (PR), or stable disease (SD) by International Uniform Response criteria. (NCT01374217)
Timeframe: Up to 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Tadalafil | 5 |
Participants With Objective Response
To determine the efficacy of the combination of Ruxolitinib + Lenalidomide in patients with Myelofibrosis (MF). Objective response rate equals Complete and Partial Response, and Clinical Improvement as defined by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Objective response rate (ORR), defined as a clinical improvement (CI), partial remission (PR), and complete remission (CR) according to the International Working Group (IWG) Criteria. Complete remission (CR): bone marrow blasts <5%, hemoglobin >/= 10, absolute neutrophil count (ANC) >/= 1000, platelets >/= 100, <2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC >/= 1000, decreased platelets by 50%, hemoglobin >/= 8.5 but < 10, <2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly >/= 50%, >/=50% reduction in MPN-SAF TSS (NCT01375140)
Timeframe: 3 cycles (28 days each) up to 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Ruxolitinib + Lenalidomide | 7 |
Serious Adverse Events
"Type, frequency, severity and timing of adverse events and their relationship to combination therapy with lenalidomide plus dexamethasone.~SAE Grade 3 indicates a severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization; disabling; limiting self care ADL SAE Grade 4 indicates a life-threatening consequences; urgent intervention indicated.~SAE Grade 5 Death related to AE." (NCT01380106)
Timeframe: Data was collected for each subject for the duration of the participation in the study, ranging between 75 to 475 days.
| Intervention | Events (Number) |
|---|
| SAE Grade 3 | SAE Grade 4 | SAE Grade 5 |
|---|
| Lenalidomide 15mg | 23 | 1 | 0 |
,| Lenalidomide 25mg | 23 | 4 | 1 |
Duration Until Best Response (at Least MR or Minimal Response)
Number of days between the first day of the first cycle to best M-protein response, at least Minimal Response or higher (Partial Response, Very Good Partial Response, near Complete Response, Complete Response). (NCT01380106)
Timeframe: Data was collected for each subject for the duration of the participation in the study, ranging between 75 to 475 days.
| Intervention | Days (Mean) |
|---|
| Lenalidomide 25mg | 280.4 |
| Lenalidomide 15mg | 145.5 |
Phase 2: Percentage of Participants With Very Good Partial Response (VGPR)
VGPR as per IMWG criteria is serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 37 |
Phase 2: Time to Response
Time to first response is defined as the time from the date of first dose of study treatment to the date of the first documentation of a confirmed response (PR or better) in a participant who responded + 1 day. PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 3 mg | 0.72 |
Progression Free Survival (PFS)
PFS was defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease or to death due to any cause, whichever occurred first plus 1. PD: >=25% increase from lowest value in:serum/urine M-component; difference between involved,uninvolved FLC levels; bone marrow plasma cell percent; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. SD: not meeting criteria for CR, VGPR, PR, or PD. Participants who received ASCT or an alternate anticancer therapy were censored at the last response assessment that was SD or better before initiation of therapy. Participants without a response assessment were censored at the date of first dose. PFS was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months
| Intervention | months (Median) |
|---|
| Ixazomib 3 mg | 29.7 |
Time to Disease Progression (TTP)
Time to progression was defined as the time from the date of first dose of study treatment to the date of first documentation of PD + 1 day. Participants that did not experience PD will be censored at the last response assessment that is SD or better. PD: >=25% increase from lowest value in:serum/urine M-component; difference between involved, uninvolved FLC levels; bone marrow plasma cell percent; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development. SD: not meeting criteria for CR, VGPR, PR, or PD. Participants that received Autologous Stem Cell Transplantation (ASCT) or an alternate cancer therapy were also be censored at the last response assessment that is, SD or better prior to initiation of therapy. Participants without response assessment will be censored at the date of first dose. TTP was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months
| Intervention | months (Median) |
|---|
| Ixazomib 3 mg | 29.7 |
Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
AUC(0-72) is a measure of the area under the plasma concentration time-curve from time zero to 72 hours post-dose for ixazomib. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11
| Intervention | hour*nanogram per milliliter (hr*ng/mL) (Geometric Mean) |
|---|
| Day 1 | Day 11 |
|---|
| Phase 1: Ixazomib 3 mg | 315.450 | 1105.44 |
,| Phase 1: Ixazomib 3.7 mg | 284.576 | 1023.52 |
Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included body temperature, blood pressure and heart rate. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)
| Intervention | Participants (Count of Participants) |
|---|
| Pyrexia | Bradycardia | Orthostatic hypotension | Hypotension |
|---|
| Phase 1: Ixazomib 3 mg | 1 | 1 | 0 | 1 |
,| Phase 1: Ixazomib 3.7 mg | 3 | 0 | 1 | 1 |
Phase 1: Number of Participants With Markedly Abnormal Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)
Laboratory tests included chemistry, hematology and urinalysis. Abnormal laboratory value was assessed as an AE if the value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)
| Intervention | Participants (Count of Participants) |
|---|
| Alanine aminotransferase increased | Aspartate aminotransferase increased | Blood creatinine increased | Shift to the left | Platelet count decreased | Blood bicarbonate decreased | Anaemia | Neutropenia | Thrombocytopenia | Eosinophilia | Hypokalaemia | Hyperkalaemia | Hyperglycaemia | Hyponatraemia | Hypomagnesaemia | Hyperchloraemia | Iron deficiency anaemia |
|---|
| Phase 1: Ixazomib 3 mg | 0 | 0 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 4 | 0 | 0 | 1 | 1 |
,| Phase 1: Ixazomib 3.7 mg | 3 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 |
Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after last dose of study drug (Up to Cycle 83 - approximately 2067 days)
| Intervention | percentage of participants (Number) |
|---|
| Adverse Event | Serious Adverse Event |
|---|
| Phase 1: Ixazomib 3 mg | 100 | 71 |
,| Phase 1: Ixazomib 3.7 mg | 100 | 29 |
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Tmax: Time to reach the first maximum plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11
| Intervention | hours (Median) |
|---|
| Day 1 | Day 11 |
|---|
| Phase 1: Ixazomib 3 mg | 1.035 | 1.030 |
,| Phase 1: Ixazomib 3.7 mg | 1.000 | 0.984 |
Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16
CR as per IMWG criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR were applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein; Urine M-protein; Serum FLC assay. (NCT01383928)
Timeframe: Cycles 4, 8, and 16
| Intervention | percentage of participants (Number) |
|---|
| After 4 cycles | After 8 cycles | After 16 cycles |
|---|
| Phase 2: Ixazomib 3 mg | 49 | 64 | 92 |
Phase 2: Percentage of Participants With Stringent Complete Response (sCR)
sCR as per IMWG criteria is CR plus normal FLC ratio and absence of clonal cells in bone marrow. CR is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 22 |
Phase 2: Percentage of Participants With Minimal Response (MR)
MR as per IMWG criteria is 25%-49% reduction in serum paraprotein and 50%-89% reduction in urine light chain excretion for 6 weeks. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 6 |
Phase 1: Recommended Phase 2 Dose (RP2D)
The RP2D of ixazomib was determined after the evaluation of the available data from the phase 1 portion of the trial which included, but was not limited to analyses of efficacy results, toxicity characterization, all grades peripheral neuropathy, and treatment discontinuation. The maximum number of cycles received was 83 cycles (approximately up to 2037 days). (NCT01383928)
Timeframe: Cycle 1 (21 days)
| Intervention | mg (Number) |
|---|
| Phase 1: All Participants | 3 |
Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Year 1
The Kaplan-Meier estimate reports the percentage of participants surviving at Year 1. (NCT01383928)
Timeframe: 1 year after the first dose of study treatment
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib 3 mg | 94 |
Overall Survival
Overall survival was measured as the time from the date of first dose of study treatment to the time of death plus 1 day. For participants who did not die, survival was censored at the date of last contact. Overall Survival was analyzed using standard survival analysis techniques based on Kaplan-Meier estimates. (NCT01383928)
Timeframe: Baseline up to a follow-up of 62.1 months
| Intervention | months (Median) |
|---|
| Ixazomib 3 mg | NA |
Phase 1: Maximum Tolerated Dose (MTD)
MTD was highest dose of ixazomib given with combination drugs, at which <=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or >=Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; any >=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or <1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by >14 days; <=80% lenalidomide doses administered due to other >=Grade 2 combination study drug-related nonhematologic toxicities requiring therapy discontinuation. (NCT01383928)
Timeframe: Cycle 1 (21 days)
| Intervention | mg (Number) |
|---|
| Phase 1: All Participants | 3.7 |
Phase 1: Percentage of Participants With Best Overall Response
CR as per International Myeloma Working Group (IMWG) uniform criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Partial response(PR):>=50% reduction of serum M-protein,urinary M-protein by >=90%/to <200 mg/24 hr reduction.Near CR(nCR):positive immunofixation of serum/urine;soft tissue plasmacytomas disappearance;<=5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR was applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein greater than or equal to (>=)1 g/dL; Urine M-protein >=200 mg/24 hours; Serum FLC assay level >=10 mg/dL, provided serum FLC ratio was abnormal. (NCT01383928)
Timeframe: Baseline until end of study treatment (Up to treatment Cycle 83 - approximately 2037 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 1: Ixazomib 3 mg | 92 |
Phase 1: Rac: Accumulation Ratio of Ixazomib
The accumulation ratio (Rac) was estimated as the ratio of AUC (0-72) on Day 11 to the AUC (0-72) on Day 1. AUC (0-72) is the area under the plasma concentration-time curve from time zero to 72 hours post-dose for ixazomib. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11
| Intervention | ratio (Geometric Mean) |
|---|
| Phase 1: Ixazomib 3 mg | 3.785 |
| Phase 1: Ixazomib 3.7 mg | 3.967 |
Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve. (NCT01383928)
Timeframe: Cycle 1, Days 1 and 11
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Day 1 | Day 11 |
|---|
| Phase 1: Ixazomib 3 mg | 33.515 | 58.674 |
,| Phase 1: Ixazomib 3.7 mg | 46.946 | 51.832 |
Phase 2: Duration of Response (DOR)
DOR was measured as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as >=25% increase from lowest value in: serum/urine M-component; difference between involved, uninvolved FLC levels; bone marrow plasma cell percent; development of new bone lesions or soft tissue plasmacytomas development or increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcaemia development. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | months (Median) |
|---|
| Phase 2: Ixazomib 3 mg | 29.0 |
Phase 2: Percentage of Participants Experiencing Serious Adverse Events
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 46 |
Phase 2: Percentage of Participants With Complete Response (CR)
CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 29 |
Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR)
CR as per International Myeloma Working Group (IMWG) uniform criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. VGPR was applicable only to participants who had measurable disease defined by at least 1 of the following 3 measurements: Serum M-protein greater than or equal to (>=)1 g/dL; Urine M-protein >=200 mg/24 hours; Serum FLC assay level >=10 mg/dL, provided serum FLC ratio was abnormal. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 65 |
Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. As per Common Terminology Criteria for Adverse Events v4.0 (CTCAE), Grade 3 = AE with severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 = AE with life-threatening consequences; urgent intervention indicated and Grade 5 = Death related to AE. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 74 |
Phase 2: Percentage of Participants With Near Complete Response (nCR)
nCR as per IMWG criteria is positive immunofixation analysis of serum or urine as the only evidence of disease; appearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 10 |
Phase 2: Percentage of Participants With Overall Response (CR+VGPR+PR)
Overall response is defined as CR, VGPR or PR based on IMWG Response Criteria for malignant lymphoma. CR: disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein+urine M-protein level <100 mg/24h. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 94 |
Phase 2: Percentage of Participants With Partial Response (PR)
PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hr urinary M-protein by 90% or to <200 mg per 24 hours. (NCT01383928)
Timeframe: Baseline until end of treatment (Up to treatment Cycle 74 - approximately 1875 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 65 |
Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT01383928)
Timeframe: Baseline up to 30 days after the last dose of study drug (approximately 1905 days)
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Ixazomib 3 mg | 14 |
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1: ULN - 11.5, Gr2:>11.5 - 12.5, Gr3: 12.5 - 13.5, Gr4: >13.5. (NCT01393964)
Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
| Intervention | participants (Number) |
|---|
| Sodium High Any Grade | Sodium High Grade 3-4 | Sodium Low Any Grade | Sodium Low Grade 3-4 | Potassium High Any Grade | Potassium High Grade 3-4 | Potassium Low Any Grade | Potassium Low Grade 3-4 | Bicarbonate Any Grade | Bicarbonate Grade 3-4 | Calcium High Any Grade | Calcium High Grade 3-4 | Calcium Low Any Grade | Calcium Low Grade 3-4 | Glucose High Any Grade | Glucose High Grade 3-4 | Glucose Low Any Grade | Glucose Low Grade 3-4 |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 2 | 0 | 5 | 0 | 4 | 3 | 6 | 1 | 6 | 0 | 3 | 1 | 8 | 2 | 7 | 3 | 1 | 0 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 2 | 0 | 2 | 1 | 2 | 0 | 2 | 0 | 5 | 0 | 1 | 0 | 4 | 0 | 7 | 3 | 1 | 0 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 3 | 0 | 6 | 1 | 2 | 0 | 5 | 2 | 8 | 0 | 0 | 0 | 6 | 1 | 9 | 4 | 0 | 0 |
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:NCT01393964)
Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
| Intervention | participants (Number) |
|---|
| Hemoglobin Any Grade | Hemoglobin Grade 3-4 | Platelet Count Any Grade | Platelet Count Grade 3-4 | Leukocytes Any Grade | Leukocytes Grade 3-4 | Lymphocytes (Abs) Any Grade | Lymphocytes (Abs) Grade 3-4 | Neutrophil Count (Abs) Any Grade | Neutrophil Count (Abs) Grade 3-4 |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 9 | 6 | 8 | 2 | 6 | 2 | 9 | 5 | 6 | 2 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 8 | 0 | 7 | 0 | 8 | 3 | 8 | 6 | 6 | 3 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 9 | 2 | 8 | 2 | 8 | 1 | 9 | 9 | 5 | 1 |
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN. (NCT01393964)
Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
| Intervention | participants (Number) |
|---|
| ALP Any Grade | ALP Grade 3-4 | AST Any Grade | AST Grade 3-4 | ALT Any Grade | ALT Grade 3-4 | Bilirubin Any Grade | Bilirubin Grade 3-4 | Creatinine Any Grade | Creatinine Grade 3-4 | Albumin Any Grade | Albumin Grade 3-4 |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 7 | 0 | 5 | 0 | 5 | 0 | 2 | 0 | 9 | 9 | 7 | 0 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 0 | 0 | 3 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 3 | 0 | 2 | 0 | 5 | 0 | 1 | 0 | 9 | 2 | 7 | 0 |
Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. (NCT01393964)
Timeframe: Day 1 of Cycle 1 to 28 days post dose
| Intervention | mL/kg (Geometric Mean) |
|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 59.4 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 54.6 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 61.2 |
Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. (NCT01393964)
Timeframe: Day 1 of Cycle 1 to 28 days post dose
| Intervention | µg/mL (Geometric Mean) |
|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 217 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 226 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 218 |
Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. (NCT01393964)
Timeframe: Day 1 of Cycle 1 to 28 days post dose
| Intervention | mL/h/kg (Geometric Mean) |
|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 0.215 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 0.166 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 0.195 |
Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group. (NCT01393964)
Timeframe: Day 1 of Cycle 1 to 28 days post dose
| Intervention | h (Mean) |
|---|
| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 204 |
| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 237 |
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 218 |
Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method
The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value ≥ 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group (NCT01393964)
Timeframe: Day 1 of Cycle 1 to 28 days post dose
| Intervention | µg*h/mL (Geometric Mean) |
|---|
| AUC (0-T) | AUC (INF) |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 45937 | 51227 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 39559 | 46401 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 50080 | 60255 |
Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose.
Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cycle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment. (NCT01393964)
Timeframe: From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years
| Intervention | participants (Number) |
|---|
| Baseline ADA Positive | On-Study ADA Positive | Positive at Cycle 2 pre-dose | Persistent Positive | Last Sample Positive | Other Positive | On-Study ADA Negative |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 0 | 1 | 1 | 0 | 1 | 0 | 5 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 1 | 2 | 2 | 0 | 1 | 1 | 4 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 0 | 1 | 0 | 0 | 0 | 1 | 3 |
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. (NCT01393964)
Timeframe: From first dose (Day 1) to last dose plus 60 days (Assessed up to July 2016, approximately 54 months)
| Intervention | participants (Number) |
|---|
| Deaths | Any SAE | AEs Leading to Discontinuation |
|---|
| Elotuzumab + LD in End Stage Renal Disease (ESRD) Participants | 0 | 7 | 1 |
,| Elotuzumab + LD in Normal Renal Function (NRF) Participants | 0 | 3 | 1 |
,| Elotuzumab + LD in Severe Renal Impairment (SRI) Participants | 0 | 5 | 4 |
Time-to-Progression (TTP)
(NCT01401322)
Timeframe: 12 weeks
| Intervention | Days (Median) |
|---|
| Lenalidomide 50 mg/Day x 28 Days | 20 |
Rate of Minimal Residual Disease (MRD) by Flow Cytometry
Response is assessed by the International Myeloma Working Group Criteria. Complete response is negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains. Immunophenotyping is performed by multi-parametric flow cytometry. (NCT01402284)
Timeframe: Day 100
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 44.4 |
Percentage of Responders With Duration of Response (DOR) at 48 Months
Response is assessed by the International Myeloma Working Group Criteria. DOR is measured from the time measurement criteria are met for a partial response or better until first date that recurrent or progressive disease is objectively documented. Partial response is ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24h. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. (NCT01402284)
Timeframe: 48 months
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 81.1 |
Overall Survival (OS) Rate
OS is defined as the time of start of treatment to death from any cause. (NCT01402284)
Timeframe: up to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 89.5 |
Overall Response Rate
Response is assessed by the International Myeloma Working Group Criteria. Patients who attained a partial response or better (BoR) response by the end of induction. Partial response is ≥50% reduction of serum M-protein and reduction in 24h urinary M-protein. (NCT01402284)
Timeframe: 48.3 months
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 97.8 |
Complete Response (CR) and Minimal Residual Disease Neg (MRDneg) CR Rates at Treatment Intervals With Carfilzomib, Lenalidomide & Dexamethasone (CRd) in New Multiple Myeloma Patients After 8 Cycles of Induction, 1 Year Maintenance, and 2 Years Maintenance
Response is assessed by the International Myeloma Working Group Criteria. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains (FLC). Complete response is negative immunofixation on serum, and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. Stringent complete response (sCR) is normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. Near complete response (nCR) is the absence of myeloma protein on electrophoresis, independent of immunofixation status. Very good partial response (VGPR) is serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24h. Overall response rate (ORR) is patients who attained a partial response (PR) (≥50% reduction of serum M-protein and reduction in 24h urinary M-protein) or better (BoR) response. (NCT01402284)
Timeframe: up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| sCR/CR after 8 cycles | MRDnegCR after 8 cycles | nCR after 8 cycles | ≥VGPR after 8 cycles | ORR after 8 cycles | sCR after 8 cycles | sCR/CR after 1 year | sCR after 1 year | CR after 1 year | MRDnegCR after 1 year' | nCR after 1 year | ≥VGPR after 1 year | ORR after 1 year | sCR/CR after 2 years | sCR after 2 years | CR after 2 years | MRDnegCR after 2 years* | nCR after 2 years | ≥VGPR after 2 years | ORR after 2 years |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 46.7 | 44.4 | 20 | 89 | 97.8 | 46.7 | 62.2 | 60.0 | 2.2 | 53.5 | 11.1 | 89 | 97.8 | 64.4 | 62.2 | 2.2 | 46.2 | 11.1 | 91.1 | 97.8 |
Number of Participants With Serious and Non-serious Adverse Events
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01402284)
Timeframe: 4 years and 9 months and 2 days
| Intervention | Participants (Count of Participants) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 45 |
Progression Free Survival (PFS) at 48 Months
PFS is defined as time of start of treatment to time of progression or death, whichever occurs first. Response is assessed by the International Myeloma Working Group Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder. (NCT01402284)
Timeframe: 48 months
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib, Lenalidomide, and Dexamethasone | 79.2 |
Number of Dose Limiting Toxic Events (DLT) of Lenalidomide Given in Combination With Chlorambucil.
(NCT01403246)
Timeframe: At maximum 8 months from induction therapy start
| Intervention | Toxic events (Number) |
|---|
| Study Group | 0 |
Incidences of Grades II-IV Acute GVHD and Limited or Extensive Chronic GVHD
(NCT01419795)
Timeframe: Assessed up to 30 days after completion of study treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lenalidomide, Rituximab) | 0 |
Improvement in Overall Survival of Patients Receiving Lenalidomide With or Without Rituximab in Comparison to Historical Controls Managed by Single or Multiple Chemotherapeutic Agents or Donor Lymphocyte Infusion (DLI) (Cohort 1)
Estimated using the Kaplan-Meier method in all cohorts. (NCT01419795)
Timeframe: 12 months
| Intervention | survival probability (Number) |
|---|
| Arm I (Lenalidomide, Rituximab) | 0.33 |
Rate of Response (CR, PR, or SD) and Time to Progression
Estimated using the Kaplan-Meier method in all cohorts. Assessed at day 100. (NCT01419795)
Timeframe: Assessed up to 18 months
| Intervention | progression free survival probability (Number) |
|---|
| Arm I (Lenalidomide, Rituximab) | 0.67 |
Grade III-IV Toxicity in Patients Receiving Lenalidomide With or Without Rituximab
(NCT01419795)
Timeframe: Assessed up to 30 days after completion of study treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lenalidomide, Rituximab) | 2 |
Comparison of Rates of Overall Response and Complete Remission Between the First, Second, and Third Cohorts
(NCT01419795)
Timeframe: Assessed up to 18 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lenalidomide, Rituximab) | 0 |
Comparison of Incidences of Adverse Events Between the First, Second, and Third Cohorts
(NCT01419795)
Timeframe: Assessed up to 30 days after completion of study treatment
| Intervention | Number of adverse events (Number) |
|---|
| Arm I (Lenalidomide, Rituximab) | 7 |
Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups (NCT01421186)
Timeframe: 56 days
| Intervention | mg*days/L (Mean) |
|---|
| 4 mg/kg QW | 3307.57 |
| 8 mg/kg QW | 7970.15 |
| 16 mg/kg QW | 18178.57 |
Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202
PK analysis for MOR202 4, 8 and 16 mg/kg IV once weekly dose groups only, since serum concentrations of MOR202 were substantially affected by target mediated drug disposition effects for remaining dose groups (NCT01421186)
Timeframe: up to 7 days after last MOR202 dose
| Intervention | µg/mL (Mean) |
|---|
| 4 mg/kg QW | 137.86 |
| 8 mg/kg QW | 311.67 |
| 16 mg/kg QW | 681.53 |
Progression-free Survival
Progression-free survival (Kaplan Meier estimates) (NCT01421186)
Timeframe: patients were observed up to 36 months
| Intervention | months (Median) |
|---|
| Part A: MOR03087 Biweekly Dose Escalation | 1.1 |
| Part B: MOR03087 Weekly Dose Escalation | 2.1 |
| Part C: MOR03087 Plus Dexamethasone | 8.4 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 15.9 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 26.7 |
Time to Progression
Time to Progression (Kaplan Meier estimate) (NCT01421186)
Timeframe: patients were observed for up to 36 months
| Intervention | months (Median) |
|---|
| Part A: MOR03087 Biweekly Dose Escalation | 1.1 |
| Part B: MOR03087 Weekly Dose Escalation | 2.1 |
| Part C: MOR03087 Plus Dexamethasone | 8.4 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 15.9 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 33.2 |
Determination of Maximum Tolerated Dose and / or Recommended Dose and Dosing Regimen of MOR03087
"as monotherapy~in combination with dexamethasone~in combination with pomalidomide + dexamethasone~in combination with lenalidomide + dexamethasone" (NCT01421186)
Timeframe: First cycle of treatment
| Intervention | mg/kg (Number) |
|---|
| Part A: MOR03087 Biweekly Dose Escalation | 16 |
| Part B: MOR03087 Weekly Dose Escalation | 16 |
| Part C: MOR03087 Plus Dexamethasone | 16 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 16 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 16 |
Duration of Response
Duration of response (Kaplan Meier estimates) (NCT01421186)
Timeframe: patients were observed up to 36 months
| Intervention | months (Median) |
|---|
| Part C: MOR03087 Plus Dexamethasone | 16.7 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 21.2 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 32.2 |
Number of Participants Who Develop Anti-MOR03087 Antibodies
Number of participants who develop anti-MOR03087 antibodies, a measure of immunogenicity (NCT01421186)
Timeframe: during treatment period, maximum 3 years after 1st dose
| Intervention | Participants (Count of Participants) |
|---|
| Part A: MOR03087 Biweekly Dose Escalation | 0 |
| Part B: MOR03087 Weekly Dose Escalation | 0 |
| Part C: MOR03087 Plus Dexamethasone | 0 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 0 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 0 |
Overall Response Rate
number (#) of patients responding (# stringent complete response + # complete response + # very good partial response + # partial response) (NCT01421186)
Timeframe: maximum 3 years after 1st dose
| Intervention | Participants (Count of Participants) |
|---|
| Part A: MOR03087 Biweekly Dose Escalation | 0 |
| Part B: MOR03087 Weekly Dose Escalation | 0 |
| Part C: MOR03087 Plus Dexamethasone | 5 |
| Part D: MOR03087 Plus Pomalidomide + Dexamethasone | 10 |
| Part E: MOR03087 Plus Lenalidomide + Dexamethasone | 11 |
Overall Response Rate (ORR)
Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR). (NCT01442714)
Timeframe: 203 days
| Intervention | Participants (Count of Participants) |
|---|
| Azacitidine Plus Lenalidomide | 5 |
Overall Survival
Survival was measured from the 1st day of azacitidine treatment to death from any cause. (NCT01442714)
Timeframe: 462 Days
| Intervention | months (Median) |
|---|
| Azacitidine Plus Lenalidomide | 5 |
Progression-free Survival in Patients With Previously Treated Hodgkin's Lymphoma Receiving Combined Lenalidomide and Panobinostat
Determined from the date of start of therapy to death from any cause or censored at the last date the patient is known to be alive (NCT01460940)
Timeframe: 3-5 years
| Intervention | months (Median) |
|---|
| Lenalidomide and Panobinostat | 3.8 |
Determine the Overall Response Rate (ORR), Including Complete Responses (CR) and Partial Responses (PR)
Overall response rate (CR + PR) will be determined using the International response criteria with combined panobinostat and lenalidomide in patients with relapsed or refractory Hodgkin's lymphoma. (NCT01460940)
Timeframe: up to 24 months
| Intervention | percentage of patients (Number) |
|---|
| Lenalidomide and Panobinostat | 16.7 |
Assess the Safety and Tolerability of Combined Lenalidomide and Panobinostat in Patients With Previously Treated Hodgkin's Lymphoma.
Safety and tolerability will be assessed for patients using the NIH-NCI Common Terminology Criteria (CTCAE) version 4.0 (NCT01460940)
Timeframe: up to 24 months
| Intervention | percentage of patients (Number) |
|---|
| neutropenia | thrombocytopenia | febrile neutropenia | hypophosphatemia |
|---|
| Lenalidomide and Panobinostat | 58.3 | 41.7 | 25.0 | 25.0 |
Number of Participants Evaluated for Toxicity
All toxicities with a maximum grade and status of ≥ grade 2 will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (NCT01463670)
Timeframe: every 28 days before initiation of a new cycle through study completion until disease progression up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide | 11 |
Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01463670)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Partial Response | Minor Response | Stable Disease | Progression of Disease |
|---|
| Lenalidomide | 1 | 1 | 7 | 1 |
Overall Response Rate
The primary endpoint of overall response rate will be estimated and a 95% confidence interval will be estimated via binomial proportions. (NCT01472562)
Timeframe: 30 months
| Intervention | percentage of patients (Number) |
|---|
| All Patients | 92 |
Number of Participants With Complete Response (CR)
Number of participants with complete response, the disappearance of all signs of cancer in response to treatment. (NCT01496976)
Timeframe: 3 Months
| Intervention | Participants (Count of Participants) |
|---|
| Immunotherapy | 1 |
Number of Participants With Overall Survival (OS)
Overall survival will be summarized with the Kaplan-Meier curve. (NCT01496976)
Timeframe: 36 Months
| Intervention | participants (Number) |
|---|
| Immunotherapy | 24 |
Number of Participants With Partial Response (PR)
The primary endpoint for this trial is the combined complete and partial response rate to the protocol therapy at 3 months, which is also the end of Cycle 3. The objective response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution. (NCT01496976)
Timeframe: 3 Months
| Intervention | participants (Number) |
|---|
| Immunotherapy | 33 |
Rate of Progression/Relapse Free Survival (PFS)
Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier. (NCT01496976)
Timeframe: Up to 56 months
| Intervention | months (Median) |
|---|
| Immunotherapy | 54.4 |
Objective Response Rate (ORR)
ORR at 3 months. Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. Objective response = Complete Response (disappearance of all target lesions) + Partial Response (>=30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) (NCT01497496)
Timeframe: 3 Months
| Intervention | percentage of participants (Number) |
|---|
| Immunotherapy | 48.3 |
Overall Survival
OS is calculated for all patients from the date of initial registration to date of death due to any cause. The follow- up for patients last known to be alive is censored at the date of last contact. OS will be estimated for each of the three arms using the Kaplan-Meier method. (NCT01522976)
Timeframe: Up to 5 years
| Intervention | Days (Median) |
|---|
| Arm 1: Azacitidine/Lenalidomide | 588 |
| Arm 2: Azacitidine | 449 |
| Arm 3: Azacitidine/Vorinostat | 527 |
Relapse-free Survival
RFS is calculated for patients who have achieved a response. RFS will be measured from the date of response to the date of first documentation of relapse from response (as defined in the primary objective), or death due to any cause. The follow-up for patients last known to be alive and without report of relapse is censored at the date of last contact. RFS will be estimated for each of the three arms using the Kaplan-Meier method. (NCT01522976)
Timeframe: Up to 5 years
| Intervention | Days (Median) |
|---|
| Arm 1: Azacitidine/Lenalidomide | 435 |
| Arm 2: Azacitidine | 311 |
| Arm 3: Azacitidine/Vorinostat | 455 |
Response Rate (Phase II)
A response is any of complete hematological remission, partial remission, or hematologic improvement. (NCT01522976)
Timeframe: Up to 5 years
| Intervention | percentage of patients having a response (Number) |
|---|
| Arm 1: Azacitidine/Lenalidomide | 49 |
| Arm 2: Azacitidine | 38 |
| Arm 3: Azacitidine/Vorinostat | 27 |
Pre-study Cytogenetic Abnormalities
Cytogenetic risk group is used to identify cytogenetic abnormalities. (NCT01522976)
Timeframe: Up to 5 years
| Intervention | participants (Number) |
|---|
| Good/very good | Intermediate | Poor | Very poor | Missing |
|---|
| Arm 1: Azacitidine/Lenalidomide | 35 | 13 | 8 | 23 | 14 |
,| Arm 2: Azacitidine | 29 | 16 | 10 | 23 | 14 |
,| Arm 3: Azacitidine/Vorinostat | 34 | 18 | 8 | 19 | 13 |
Toxicity Rate
Adverse events that are possibly, probably or definitely related to study drug are reported. (NCT01522976)
Timeframe: Up to 5 years
| Intervention | Participants (Number) |
|---|
| Abdominal infection | Abdominal pain | Acute kidney injury | Adult respiratory distress syndrome | Alanine aminotransferase increased | Anemia | Anorectal infection | Anorexia | Apnea | Ascites | Aspartate aminotransferase increased | Ataxia | Back pain | Blood and lymphatic system disorders - Other | Blood bilirubin increased | Bronchial infection | CD4 lymphocytes decreased | Cardiac arrest | Catheter related infection | Cecal infection | Cholecystitis | Colitis | Confusion | Constipation | Creatinine increased | Dehydration | Delirium | Diarrhea | Dizziness | Dyspnea | Epistaxis | Esophageal pain | Esophagitis | Fall | Fatigue | Febrile neutropenia | Fever | Flushing | Gastric hemorrhage | Gastrointestinal pain | General disorders and admin site conditions-Other | Generalized muscle weakness | Hallucinations | Headache | Heart failure | Hematoma | Hematuria | Hyperglycemia | Hypernatremia | Hypertension | Hyperuricemia | Hypoalbuminemia | Hypokalemia | Hypomagnesemia | Hyponatremia | Hypophosphatemia | Hypotension | Hypoxia | Infections and infestations - Other, specify | Intracranial hemorrhage | Investigations - Other, specify | Leukocytosis | Lower gastrointestinal hemorrhage | Lung infection | Lymphocyte count decreased | Lymphocyte count increased | Mucosal infection | Mucositis oral | Nausea | Neutrophil count decreased | Pain | Papulopustular rash | Pericardial effusion | Platelet count decreased | Pneumonitis | Pruritus | Pulmonary edema | Purpura | Rash maculo-papular | Renal and urinary disorders - Other, specify | Respiratory failure | Sepsis | Sinus bradycardia | Skin infection | Soft tissue infection | Sudden death NOS | Syncope | Thromboembolic event | Tooth infection | Upper gastrointestinal hemorrhage | Upper respiratory infection | Urinary tract infection | Vascular disorders - Other, specify | Vomiting | Weight loss | White blood cell decreased |
|---|
| Arm 1: Azacitidine/Lenalidomide | 1 | 1 | 0 | 1 | 0 | 48 | 0 | 4 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 2 | 5 | 0 | 5 | 1 | 4 | 0 | 0 | 1 | 0 | 9 | 16 | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 3 | 4 | 1 | 5 | 1 | 4 | 0 | 4 | 1 | 1 | 0 | 0 | 4 | 14 | 0 | 0 | 1 | 1 | 69 | 1 | 1 | 1 | 61 | 0 | 1 | 0 | 1 | 13 | 0 | 0 | 4 | 1 | 3 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 48 |
,| Arm 2: Azacitidine | 0 | 0 | 0 | 0 | 0 | 37 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 6 | 11 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 9 | 1 | 0 | 0 | 2 | 48 | 0 | 0 | 0 | 46 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 2 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 34 |
,| Arm 3: Azacitidine/Vorinostat | 0 | 3 | 1 | 0 | 5 | 44 | 1 | 3 | 1 | 1 | 3 | 1 | 0 | 1 | 3 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 3 | 1 | 3 | 0 | 3 | 1 | 1 | 0 | 1 | 14 | 13 | 2 | 1 | 1 | 1 | 0 | 3 | 1 | 1 | 1 | 1 | 2 | 2 | 0 | 2 | 1 | 0 | 1 | 0 | 4 | 2 | 3 | 1 | 5 | 0 | 0 | 0 | 2 | 2 | 3 | 1 | 1 | 0 | 2 | 63 | 0 | 0 | 0 | 64 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 3 | 0 | 2 | 0 | 0 | 4 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 44 |
Number of Participants With Response
Overall response defined as number of participants with International Myeloma Working Group Uniform Response Criteria: Complete Response (CR): Negative immunofixation serum & urine, Disappearance soft tissue plasmacytomas & =/<5% plasma cells in bone marrow; Stringent Complete Remission: CR + Normal Normal free light chain (FLC) ratio & Absence clonal cells in bone marrow by Immunohistochemistry/ immunofluorescence; Very Good Partial Response (VGPR): Serum & urine M-protein detectable by immunofixation but not on electrophoresis or 90%> reduction in serum M-protein +urine M-protein level <100mg per 24 hour; Partial Remission (PR): =/>50% reduction serum M-protein & reduction in 24-hour urinaryMprotein by >90% or to < 200mg per 24 hour, =/>50% reduction of serum M-protein & reduction in 24-hour urinary Mprotein by >90%/or <200mg, and if present at baseline, a >50% reduction in size of soft tissue plasmacytomas; Stable Disease: Not CR, VGPR, PR Or Progressive disease (NCT01531998)
Timeframe: Evaluated after eight cycles of 21 days.
| Intervention | participants (Number) |
|---|
| Complete Remission (CR) | Stringent Complete Remission | Very good partial remission (VGPR) | Partial Remission (PR) | Stable Disease |
|---|
| Siltuximab + Bortezomib + Lenalidomide | 2 | 0 | 2 | 6 | 0 |
Maximum Tolerated Dose (MTD) of Siltuximab
Maximum tolerated dose (MTD) defined as follows: At first dose level, if greater than 1 out of 3 patients or greater than 1 out of 6 patients experience dose limiting toxicity (DLT), the dose level exceeds the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) defined as toxicities graded in severity according to the guidelines outlined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. (NCT01531998)
Timeframe: 21 days
| Intervention | mg/kg (Number) |
|---|
| Siltuximab + Bortezomib + Lenalidomide | 8.3 |
Pharmacokinetic Parameters of Lenalidomide
Concentration of lenalidomide obtained from any day between day 5 and 21 of the first cycle of chemotherapy in nanograms per mL. (NCT01553149)
Timeframe: Between days 5-21 of course 1 and each dose reduction
| Intervention | nanograms per mL (Median) |
|---|
| Arm I (Low-dose Lenalidomide) | 15.1 |
| Arm II (High-dose Lenalidomide) | 178.8 |
Overall Survival [OS]
Estimated 3-year overall survival is calculated as the time from study enrollment to death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored at that time. (NCT01553149)
Timeframe: Up to 3 years after study enrollment
| Intervention | Percent Probability (Number) |
|---|
| Arm I (Low-dose Lenalidomide) | 94.59 |
| Arm II (High-dose Lenalidomide) | 91.74 |
Event-free Survival [EFS]
Estimated 3-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT01553149)
Timeframe: Up to 3 years after study enrollment
| Intervention | Percent Probability (Number) |
|---|
| Arm I (Low-dose Lenalidomide) | 37.84 |
| Arm II (High-dose Lenalidomide) | 39.41 |
Number of Patients Who Demonstrate Complete or Partial Response
"Number of patients who demonstrate a complete or partial response as defined below:~Complete Response - Complete disappearance of all known disease for at least 4 weeks;~Partial Response - A reduction of at least 50% in the size of all measurable tumor as quantitated by the sum of the products of the largest diameters of measurable lesions when compared with that measurement at the time of study enrollment and maintained for at least 4 weeks." (NCT01553149)
Timeframe: 26 cycles of chemotherapy - up to 3 years after enrollment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Low-dose Lenalidomide) | 4 |
| Arm II (High-dose Lenalidomide) | 4 |
Number of Patients Who Demonstrate Early Progression
Number of patients with disease progression during the first six months of protocol therapy. Disease progression is defined as ≥ 25% increase in the sum of the products of the largest diameters of the measurable lesions or the appearance of one or more new lesions when compared with the measurements of lesions at the time of enrollment. (NCT01553149)
Timeframe: Up to 180 days after enrollment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Low-dose Lenalidomide) | 6 |
| Arm II (High-dose Lenalidomide) | 4 |
Number of Patients With Toxic Events After 2 Dose Reductions
Number of patients who have an additional significant toxicity coded using Common Terminology Criteria for Adverse Events Version 5.0 after experiencing two dose reductions from their assigned treatment dose. (NCT01553149)
Timeframe: While receiving protocol therapy up to 3 years after study enrollment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Low-dose Lenalidomide) | 2 |
| Arm II (High-dose Lenalidomide) | 16 |
Stem Cells Collection
At the end of the Car Phase, all participants underwent stem cell collection. (NCT01559935)
Timeframe: At the end of the Car Phase, prior to the start of the BiRD Phase, on average after 162 days.
| Intervention | Number of stem cells collected per Kg (Mean) |
|---|
| Car-BiRD Therapy | 12854635 |
Response to Car-BiRD Treatment.
"The best response for all patients who had at least one dose of drug was measured.~Response categories:~Stringent Complete Response (sCR), Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Progressive Disease (PD), Stable Disease (SD).~The response is evaluated based on the IMWG criteria." (NCT01559935)
Timeframe: From baseline to best response, up to 116 weeks.
| Intervention | Participants (Count of Participants) |
|---|
| sCR/CR | VGPR | PR | SD | PD | Not Evaluable |
|---|
| Car-BiRD Therapy | 28 | 31 | 11 | 1 | 0 | 1 |
Event Free Survival
an event is defined by coming off protocol for any reason, including progression of disease, lack of disease response, regimen intolerability, withdrawal of consent or death. (NCT01559935)
Timeframe: From date of study enrollment until the date of removal of study due to progression of disease, toxicity or withdrawal of consent, up to 1222 days.
| Intervention | Days (Median) |
|---|
| Car-BiRD Therapy | 401.5 |
Progression Free Survival
Progression was defined using the IMWG criteria. (NCT01559935)
Timeframe: From start of study drug until first incidence of progression, up to 1222 days.
| Intervention | months (Median) |
|---|
| Car-BiRD Therapy | 18.3 |
Duration of Response (DOR)
DOR was measured as the time in months from the date of first documentation of a confirmed response of PR or better (CR [including sCR] + PR+ VGPR) to the date of the first documented disease progression (PD) among participants who responded to the treatment. Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 38 months
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 26.0 |
| Placebo + Lenalidomide + Dexamethasone | 21.7 |
Overall Response Rate (ORR) as Assessed by the IRC
ORR was defined as the percentage of participants with Complete Response (CR) including stringent complete response (sCR), very good partial response (VGPR) and Partial Response (PR) assessed by the IRC using IMWG criteria. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months(approximate median follow-up 15 months)
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 78.3 |
| Placebo + Lenalidomide + Dexamethasone | 71.5 |
Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)
The EORTC-QLQ-MY-20 is a patient-completed, 20-question quality of life questionnaire that has 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). The participant answers questions about their health during the past week using a 4-point scale where 1=Not at All to 4=Very Much. A negative change from Baseline indicates improvement. Scores are linearly transformed to a 0-100 scale. Higher scores on the symptom scales (e.g. Disease Symptoms, Side Effects of Treatment) represent higher levels of symptomatology or problems. High scores for Body Image and Future Perspective represent better quality of life or functioning. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)
| Intervention | score on a scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: EOT | Side Effects of Treatment: Baseline | Side Effects of Treatment: EOT | Side Effects of Treatment: Last Follow-up | Body Image: Baseline | Body Image: EOT | Body Image: Last Follow-up | Future Perspective: Baseline | Future Perspective: EOT | Future Perspective: Last Follow-up |
|---|
| Placebo + Lenalidomide + Dexamethasone | 30.41 | -2.58 | 17.97 | 4.43 | 37.04 | 79.48 | -5.38 | -33.3 | 60.26 | -2.75 | -11.11 |
Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).The EORTC-QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement. Scores are linearly transformed to a 0-100 scale. High scores for the global and functional domains indicate higher quality of life or functioning. Higher scores on the symptom scales represent higher levels of symptomatology or problems. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)
| Intervention | score on a scale (Mean) |
|---|
| Global Health Index: Baseline | Global Health Index: End of Treatment | Global Health Index: Last Follow-up | Physical Functioning: Baseline | Physical Functioning: EOT | Physical Functioning: Last Follow-up | Role Functioning: Baseline | Role Functioning: EOT | Role Functioning: Last Follow-up | Emotional Functioning: Baseline | Emotional Functioning: EOT | Emotional Functioning: Last Follow-up | Cognitive Functioning: Baseline | Cognitive Functioning: EOT | Cognitive Functioning: Last Follow-up | Social Functioning: Baseline | Social Functioning: EOT | Social Functioning: Last Follow-up | Fatigue: Baseline | Fatigue: EOT | Fatigue: Last Follow-up | Pain: Baseline | Pain: EOT | Pain: Last Follow-up | Nausea and Vomiting: Baseline | Nausea and Vomiting: EOT | Nausea and Vomiting: Last Follow-up | Dyspnea: Baseline | Dyspnea: EOT | Dyspnea: Last Follow-up | Insomnia: Baseline | Insomnia: EOT | Insomnia: Last Follow-up | Appetite Loss: Baseline | Appetite Loss: EOT | Appetite Loss: Last Follow-up | Constipation: Baseline | Constipation: EOT | Constipation: Last Follow-up | Diarrhea: Baseline | Diarrhea: EOT | Diarrhea: Last Follow-up | Financial Difficulties: Baseline | Financial Difficulties: EOT | Financial Difficulties: Last Follow-up |
|---|
| Placebo + Lenalidomide + Dexamethasone | 56.4 | -6.0 | 16.7 | 67.3 | -6.2 | 0.0 | 64.4 | -8.6 | -16.7 | 75.3 | -6.1 | -25.0 | 81.6 | -5.8 | -50.0 | 75.3 | -7.9 | 0.0 | 39.5 | 6.7 | 22.2 | 38.5 | 3.8 | 0.0 | 6.0 | 0.6 | 33.3 | 23.7 | 2.3 | 0.0 | 30.5 | -0.5 | 33.3 | 15.3 | 6.5 | 0.0 | 13.5 | 2.2 | 33.3 | 8.1 | 10.8 | 0.0 | 18.6 | 1.3 | -33.3 |
Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)
The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).The EORTC-QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement. Scores are linearly transformed to a 0-100 scale. High scores for the global and functional domains indicate higher quality of life or functioning. Higher scores on the symptom scales represent higher levels of symptomatology or problems. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)
| Intervention | score on a scale (Mean) |
|---|
| Global Health Index: Baseline | Global Health Index: End of Treatment | Physical Functioning: Baseline | Physical Functioning: EOT | Role Functioning: Baseline | Role Functioning: EOT | Emotional Functioning: Baseline | Emotional Functioning: EOT | Cognitive Functioning: Baseline | Cognitive Functioning: EOT | Social Functioning: Baseline | Social Functioning: EOT | Fatigue: Baseline | Fatigue: EOT | Pain: Baseline | Pain: EOT | Nausea and Vomiting: Baseline | Nausea and Vomiting: EOT | Dyspnea: Baseline | Dyspnea: EOT | Insomnia: Baseline | Insomnia: EOT | Appetite Loss: Baseline | Appetite Loss: EOT | Constipation: Baseline | Constipation: EOT | Diarrhea: Baseline | Diarrhea: EOT | Financial Difficulties: Baseline | Financial Difficulties: EOT |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 58.4 | -6.0 | 70.0 | -4.7 | 68.4 | -8.6 | 75.1 | -2.1 | 81.9 | -7.6 | 77.9 | -6.9 | 38.4 | 6.0 | 38.0 | 2.7 | 5.0 | 3.4 | 21.2 | 5.7 | 27.4 | 0.9 | 16.9 | 4.7 | 12.2 | -1.3 | 6.3 | 17.2 | 16.7 | 0.5 |
Time to Progression (TTP) as Assessed by the IRC
TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD) as assessed by the IRC using IMWG criteria. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 22.4 |
| Placebo + Lenalidomide + Dexamethasone | 17.6 |
PFS in High-Risk Participants
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first. Response was assessed by independent review committee (IRC) using IMWG response criteria. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis. (NCT01564537)
Timeframe: From date of randomization until disease progression or death up to approximately 38 months (approximate median follow-up 15 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 18.7 |
| Placebo + Lenalidomide + Dexamethasone | 9.3 |
Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC
Response was assessed by the IRC using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 48.1 |
| Placebo + Lenalidomide + Dexamethasone | 39.0 |
Overall Response Rate in Participants Defined by Polymorphism
Data is reported for percentage of participants defined by polymorphism defined by polymorphisms in proteasome genes, such as polymorphism P11A in PSMB1 gene. Percentages are rounded off to single decimal. (NCT01564537)
Timeframe: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 80.3 |
| Placebo + Lenalidomide + Dexamethasone | 75.7 |
Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. (NCT01564537)
Timeframe: From date of randomization until death (up to approximately 97 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 53.6 |
| Placebo + Lenalidomide + Dexamethasone | 51.6 |
Plasma Concentration Over Time for Ixazomib
(NCT01564537)
Timeframe: Pre-dose and post-dose at multiple timepoints up to Cycle 10 Day 1 (each cycle length = 28 days)
| Intervention | μg/mL (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 1, 1 Hour Post-Dose | Cycle 1 Day 1, 4 Hours Post-Dose | Cycle 1 Day 14, Pre-Dose | Cycle 2 Day 1, Pre-Dose | Cycle 2 Day 14, Pre-Dose | Cycle 3 Day 1, Pre-Dose | Cycle 4 Day 1, Pre-Dose | Cycle 5 Day 1, Pre-Dose | Cycle 6 Day 1, Pre-Dose | Cycle 7 Day 1, Pre-Dose | Cycle 8 Day 1, Pre-Dose | Cycle 9 Day 1, Pre-Dose | Cycle 10 Day 1, Pre-Dose |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 4.79 | 36.3 | 15.6 | 6.83 | 2.4 | 7.12 | 2.48 | 2.41 | 2.42 | 2.57 | 2.71 | 2.37 | 2.51 | 2.82 |
Plasma Concentration Over Time for Ixazomib
(NCT01564537)
Timeframe: Pre-dose and post-dose at multiple timepoints up to Cycle 10 Day 1 (each cycle length = 28 days)
| Intervention | μg/mL (Mean) |
|---|
| Cycle 1 Day 1, 1 Hour Post-Dose | Cycle 1 Day 1, 4 Hours Post-Dose | Cycle 1 Day 14, Pre-Dose | Cycle 2 Day 1, Pre-Dose | Cycle 2 Day 14, Pre-Dose | Cycle 3 Day 1, Pre-Dose | Cycle 4 Day 1, Pre-Dose | Cycle 5 Day 1, Pre-Dose | Cycle 6 Day 1, Pre-Dose | Cycle 7 Day 1, Pre-Dose | Cycle 8 Day 1, Pre-Dose | Cycle 9 Day 1, Pre-Dose | Cycle 10 Day 1, Pre-Dose |
|---|
| Placebo + Lenalidomide + Dexamethasone | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Change From Baseline in Pain Response
"Pain response was defined as 30% reduction from Baseline in Brief Pain Inventory-Short Form (BPI-SF) worst pain score over the last 24 hours without an increase in analgesic (oral morphine equivalents) use at 2 consecutive evaluations. The BPI-SF contains 15 items designed to capture the pain severity (worst, least, average, and now [current pain]), pain location, medication to relieve the pain, and the interference of pain with various daily activities including general activity, mood, walking activity, normal work, relations with other people, sleep, and enjoyment of life. The pain severity items are rated on a 0 to 10 scale where: 0=no pain and 10=pain as bad as you can imagine and averaged for a total score of 0 (best) to 10 (Worst)." (NCT01564537)
Timeframe: Baseline and end of treatment (EOT) (up to approximately 38 months)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline | EOT |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 345 | 145 |
,| Placebo + Lenalidomide + Dexamethasone | 351 | 153 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Eastern Cooperative Oncology Group (ECOG) performance score, laboratory values, vital sign measurements and reported adverse events (AEs) were collected and assessed to evaluate the safety of therapy throughout the study. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. (NCT01564537)
Timeframe: From the date of signing of the informed consent form through 30 days after the last dose of study drug up to approximately 115 months
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 359 | 205 |
,| Placebo + Lenalidomide + Dexamethasone | 357 | 201 |
Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)]
Overall survival is defined as the time from the date of randomization to the date of death. The high-risk participants whose myeloma carried del(17) subgroup was defined as the cases reported as positive for del(17) by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17) by local laboratory. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported high-risk participants with Del(17). (NCT01564537)
Timeframe: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 42.2 |
| Placebo + Lenalidomide + Dexamethasone | 29.4 |
Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression (PD) or death due to any cause, whichever occurs first. Response including PD was assessed by independent review committee (IRC) using the International Myeloma Working Group (IMWG) response criteria. PD requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl); Urine M-component (absolute increase ≥ 200 mg/24 hours); In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 10 mg/dl); Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease. Status evaluated every 4 weeks until disease progression (PD) was confirmed. (NCT01564537)
Timeframe: From date of randomization until disease progression or death up to approximately 27 months (approximate median follow-up 15 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 20.6 |
| Placebo + Lenalidomide + Dexamethasone | 14.7 |
Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)
The EORTC-QLQ-MY-20 is a patient-completed, 20-question quality of life questionnaire that has 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). The participant answers questions about their health during the past week using a 4-point scale where 1=Not at All to 4=Very Much. A negative change from Baseline indicates improvement. Scores are linearly transformed to a 0-100 scale. Higher scores on the symptom scales (e.g. Disease Symptoms, Side Effects of Treatment) represent higher levels of symptomatology or problems. High scores for Body Image and Future Perspective represent better quality of life or functioning. (NCT01564537)
Timeframe: Baseline, EOT and follow-up (up to approximately 97 months)
| Intervention | score on a scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: EOT | Disease Symptoms: Last Follow-up | Side Effects of Treatment: Baseline | Side Effects of Treatment: EOT | Body Image: Baseline | Body Image: EOT | Future Perspective: Baseline | Future Perspective: EOT |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 29.71 | -2.35 | 1.11 | 17.23 | 4.52 | 78.00 | -0.27 | 56.99 | 2.76 |
OS in High-Risk Participants
Overall survival (OS) is defined as the time from the date of randomization to the date of death. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported for high-risk participants. (NCT01564537)
Timeframe: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)
| Intervention | months (Median) |
|---|
| Ixazomib+ Lenalidomide + Dexamethasone | 46.9 |
| Placebo + Lenalidomide + Dexamethasone | 30.9 |
Percentage of Participants With Minimal Residual Disease (MRD)Negative Complete Response (CR) Per International Myeloma Working Group (IMWG) Criteria
MRDnegative Complete Response (CR) per the IMWHG criteria is defined as absence of phenotypically aberrant clonal plasma cells by flow cytometry on bone marrow aspirates using the eight-color two tube approach with a minimum sensitivity of 1 in 10^5 nucleated cells or higher. (NCT01572480)
Timeframe: 8 months
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 70.4 |
Overall Response Rate
Overall response is defined as the percentage of participants who have a partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) defined by the International Myeloma Working Group Criteria for Multiple Myeloma out of all evaluable participants. PR is ≥50% reduction if serum M-protein and reduction in 24-hour(h) urinary M-protein by ≥90% or to <200mg per 24h. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria. VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis. CR is negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≥5% plasma cells in bone marrow. sCR is complete response plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. (NCT01572480)
Timeframe: time measurement criteria are met for best response until the first date that recurrent or progressive disease is met, up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Overall Response Rate | Partial Response | Very Good Partial Response | Complete Response | Stringent Complete Response |
|---|
| All Participants | 100 | 5.5 | 18.5 | 0 | 75.9 |
Percentage of Participants That Have Minimal Residual Disease (MRD)-Negative Complete Response (CR) for a Minimum of 1 Year
Percentage of participants that have Minimal Residual Disease (MRD)-negative Complete Response (CR) for a minimum of 1 year estimated along with a 95% two-sided confidence interval. MRDnegative Complete Response (CR) is defined as absence of phenotypically aberrant clonal plasma cells by flow cytometry on bone marrow aspirates using the eight-color two tube approach with a minimum sensitivity of 1 in 10^5 nucleated cells or higher. (NCT01572480)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 63 |
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01572480)
Timeframe: Date treatment consent signed to date off study, approximately 117 months and 1 day.
| Intervention | Participants (Count of Participants) |
|---|
| All Participants | 54 |
Clinical Progression Free Survival
Clinical progression was assessed by the International Myeloma Working Group Criteria for Multiple Myeloma. Progression is any one of the following: Increase of ≥25% from lowest response value in the following on 2 consecutive measurements: Serum M-component and/or (the absolute increase must be ≥0.5g/dl). The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥0.5g/dl. Urine M-component and/or (the absolute must be ≥200mg/24h. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder. (NCT01572480)
Timeframe: time from enrollment in the study until development of overt clinical multiple myeloma (end organ damage or myeloma-defining event) or death, up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 90.7 |
Biochemical Progression Free Survival
Biochemical progression free survival is defined as the time from enrollment in the study until development of overt clinical multiple myeloma (end organ damage or myeloma-defining event) or death, and progressive disease by International Myeloma Working Group (IMWG) criteria. Progression is any one of the following: Increase of ≥25% from lowest response value in the following on 2 consecutive measurements: Serum M-component and/or (the absolute increase must be ≥0.5g/dl). The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥0.5g/dl. Urine M-component and/or (the absolute must be ≥200mg/24h. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. (NCT01572480)
Timeframe: time from enrollment in the study until development of overt clinical multiple myeloma (end organ damage or myeloma-defining event) or death, and progressive disease by IMWG criteria, up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 76.6 |
Progression Free Survival
Progression free survival (PFS) is defined as days from start of high dose chemotherapy to first documented progression of disease, death due to any cause or last patient contact. (NCT01575860)
Timeframe: 12 months from start of lenalidomide maintenance
| Intervention | Participants (Count of Participants) |
|---|
| Participants without Disease Progression | Participants with Disease Progression |
|---|
| Maintenance Lenalidomide in Lymphoma | 4 | 2 |
Number of Subjects With Dose-limiting Toxicities
Dose-limiting toxicity (DLT) is defined as any grade 3 toxicity or higher that occurs during the first 28 days of therapy and is possibly, probably, or definitely related to lenalidomide maintenance. (NCT01575860)
Timeframe: 28 days (Cycle 1)
| Intervention | Participants (Count of Participants) |
|---|
| Maintenance Lenalidomide in Lymphoma | 0 |
Recording of the Occurrence of Adverse Events
(NCT01600053)
Timeframe: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first
| Intervention | participants (Number) |
|---|
| Lenalidomide | 11 |
Phase 2: Time to Progression (TTP)
TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of >=25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL) Urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL; Bone marrow plasma cell percentage: the absolute % must be >=10 %; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | NA |
Phase 2: Duration of Response
Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | NA |
Phase 1: Percentage of Participants With Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). International Myeloma Working Group (IMWG) criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Phase 1: 2 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 100.0 |
| Phase 1: 4 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 100.0 |
| Phase 1: 8 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 75.0 |
| Phase 1: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 66.7 |
Phase 2: Overall Survival (OS)
Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan Meier method. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | NA |
Phase 2: Percentage of Participants With Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). IMWG criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: greater than eqaul to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 81.3 |
Phase 2: Progression-Free Survival (PFS)
Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | NA |
Phase 2: Time to Response
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Mean) |
|---|
| Time to first response | Time to best response |
|---|
| Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 1.55 | 5.60 |
Phase 1: Time to Response
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. (NCT01615029)
Timeframe: Up to 3 years
| Intervention | Months (Mean) |
|---|
| Time to first response | Time to best response |
|---|
| Phase 1: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 2.25 | 5.47 |
,| Phase 1: 2 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 0.83 | 3.12 |
,| Phase 1: 4 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 1.14 | 12.54 |
,| Phase 1: 8 mg/kg Daratumumab + Lenalidomide and Dexamethasone | 1.27 | 9.75 |
Progression Free Survival (PFS)
"Progression was defined as any one or more of the following:~Serum M protein increase ≥ 25% from baseline (or an increase of ≥ 1 g/dL if serum M protein was ≥ 5 g/dL at baseline), with an absolute increase of ≥ 0.5 g/dL; or~Urine M protein increase ≥ 25% from baseline, with an absolute increase of ≥ 200 mg/24 hrs; or~If patient had serum M protein < 1 g/dL, urine M protein < 200 mg/24 hrs, and an involved serum free light chain level ≥ 10 mg/dL at baseline: ≥ 25% increase in the difference between involved and uninvolved serum free light chain level, with an absolute increase of ≥ 10 mg/dL; or~Bone marrow plasma cell percentage increase ≥ 25% from baseline, with the absolute plasma cell % ≥ 10%; or~New bone lesions or soft tissue plasmacytomas, or definite increase in size of existing bone lesions or soft tissue plasmacytomas; or~Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to multiple myeloma." (NCT01621672)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Revlimid | 88 |
| Observation | 71 |
Duration of Response (DOR)
DOR was defined as the length of time between the date of first documented response (PR, VGPR, or CR) and the date of first documented progressive disease (PD). According to IMWG criteria: CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01645930)
Timeframe: From date of documentation of a confirmed response to date of progressive disease, (approximately 20 months)
| Intervention | months (Median) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 12.9 |
Cmax: Maximum Observed Plasma Concentration for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
| Intervention | ng/mL (Mean) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 57.57 |
Cmax: Maximum Observed Plasma Concentration for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
| Intervention | ng/mL (Mean) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 37.57 |
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
| Intervention | hr*ng/mL (Mean) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 1746.0 |
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
| Intervention | hr*ng/mL (Mean) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 685.9 |
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
| Intervention | hours (Median) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 1.5 |
Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events
The number of participants who meet markedly abnormal criteria for vital signs, included diastolic and systolic blood pressure, heart rate, oral temperature, respiratory rate, and body weight. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
| Intervention | participants (Number) |
|---|
| Grade 1 or 2 Hypertension | Grade 2 Hypotension |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 4 | 1 |
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity
Clinically significant laboratory abnormalities were defined as any test results which were observed beyond the clinically acceptable limits as per the discretion of investigator. Clinical laboratory tests included chemistry, hematology and urinalysis tests. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
| Intervention | participants (Number) |
|---|
| Alanine Aminotransferase Increased | Aspartate Aminotransferase Increased | Blood Creatinine Increased | Haemoglobin Decreased | Neutrophil Count Decreased | Platelet Count Decreased | Anaemia | Febrile Neutropenia | Neutropenia | Thrombocytopenia | Hyperglycaemia | Hypocalcaemia | Hypokalaemia | Hypomagnesaemia | Hyponatraemia | Hypophosphataemia |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 2 | 1 | 1 | 1 | 2 | 4 | 6 | 1 | 12 | 8 | 1 | 3 | 5 | 1 | 1 | 2 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or was a medically important event. (NCT01645930)
Timeframe: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 43 | 18 |
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
(NCT01645930)
Timeframe: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
| Intervention | hours (Median) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 2.0 |
Percentage of Participants With Confirmed Best Response Category
Percentage of participants who achieve or maintain any best response category during the treatment period were reported. Best response includes complete response (CR), very good partial response (VGPR), and partial response (PR). Response was assessed according to IMWG criteria. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg per 24 hours. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour. (NCT01645930)
Timeframe: From Cycle 1, Day 1 to Cycle 3, Day 1 until disease progression (approximately 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 53.5 |
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as any of the following AEs that were considered by investigator to be possibly related to therapy: 1. Grade 4 neutropenia lasting at least 7 consecutive days; 2. Grade 3 neutropenia with fever and/or infection; 3. Grade 4 thrombocytopenia at least 7 consecutive days; 4. Grade 3 thrombocytopenia with clinically significant bleeding; 5. Platelet count <10,000/mm^3; 6. Grade 2 peripheral neuropathy with pain or ≥Grade 3 peripheral neuropathy; 7. Grade 3 or greater nausea and / or emesis despite the use of optimal anti-emetic prophylaxis; 8. Grade 3 or greater diarrhea that occurred despite maximal supportive therapy; 9. Any other Grade 3 or greater nonhematologic toxicity with the following exceptions: Grade 3 arthralgia/myalgia, <1 week Grade 3 fatigue; 10. A delay of >2 weeks in the subsequent cycle of treatment; 11. Other combination study drug-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required discontinuation of study drug. (NCT01645930)
Timeframe: Cycle 1 (up to Day 28)
| Intervention | participants (Number) |
|---|
| Ixazomib+Lenalidomide+Dexamethasone | 2 |
Overall Response Rate (CR+PR)
(NCT01649791)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Lenalidomide as Chemoprevention) | 100 |
Clinical Benefit Rate
The number of response rates in participants that have achieved MR, PR, VGPR, CR (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 20 |
The Best Overall Response Rate (ORR)
The primary endpoint will be the best overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 11 |
Response Rates
"Response Rates evaluated using the International Uniform Response Criteria the International Myeloma Working Group (2003).~CR-Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow VGPR-Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component <100 mg per 24 h PR-50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 h MR-≥ 25% but < 49% reduction of serum M protein and reduction in 24 hour urine M protein by 50 - 89%, which still exceeds 200 mg/24hrs. In addition; if present at baseline, 25-49% reduction in the size of soft tissue plasmacytomas also required No increase in size or number of lytic bone lesions.~SD-Not meeting criteria for CR, VGPR, PR or progressive disease PD-Laboratory or Biochemical Relapse increase of 25% from baseline" (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Very Good Partial Response (VGPR) | Partial Response (PR) | Minimal Response (MR) | Stable Disease (SD) | Progressive Disease (PD) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 2 | 4 | 5 | 9 | 6 | 1 |
Response Rates for Len Refractory Patients
"Response Rates evaluated using the International Uniform Response Criteria the International Myeloma Working Group (2003).~CR-Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow VGPR-Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component <100 mg per 24 h PR-50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 h MR-≥ 25% but < 49% reduction of serum M protein and reduction in 24 hour urine M protein by 50 - 89%, which still exceeds 200 mg/24hrs. In addition; if present at baseline, 25-49% reduction in the size of soft tissue plasmacytomas also required No increase in size or number of lytic bone lesions.~SD-Not meeting criteria for CR, VGPR, PR or progressive disease PD-Laboratory or Biochemical Relapse increase of 25% from baseline" (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Very Good Partial Response | Partial Response | Minimal Response | Stable Disease | Progressive Disease |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 1 | 4 | 3 | 7 | 6 | 1 |
Disease Control Rate for Lens Refractory Rate
The number of response rates in Len refractory participants with SD, MR, PR, VGPR, or CR (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 21 |
Clinical Benefit Rate for Len Refractory Patients
The number of response rates in Lens Refractory participants that have achieved MR, PR, VGPR, CR (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 15 |
Overall Response Rate for Len Refractory Patients
The primary endpoint will be the best overall response rate (ORR) (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 8 |
Disease Control Rate
The number of response rates participants with SD, MR, PR, VGPR, or CR (NCT01651039)
Timeframe: up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Panobinostat, Lenalidomide and Dexamethasone | 26 |
Plasma Concentration of Ixazomib
As prespecified in the protocol, data for this outcome measure was planned to be collected for ixazomib arm group only. (NCT01659658)
Timeframe: Cycle 1, Day 1: 1, 4 hours postdose, Day 14: 144 hours postdose; Cycle 2, Day 1: predose, Day 14: 144 hours postdose; Cycles 3 to 10, Day 1: predose (cycle length=28 days)
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1: 1 Hour Post-dose | Cycle 1 Day 14: 4 Hours Post-dose | Cycle 1 Day 14: 144 Hours Post-dose | Cycle 2 Day 1: Pre-dose | Cycle 2 Day 14: 144 Hours Post-dose | Cycle 3 Day 1: Pre-dose | Cycle 4 Day 1 Pre-dose | Cycle 5 Day 1 Pre-dose | Cycle 6 Day 1: Pre-dose | Cycle 7 Day 1: Pre-dose | Cycle 8 Day 1: Pre-dose | Cycle 9 Day 1: Pre-dose | Cycle 10 Day 1: Pre-dose |
|---|
| Arm A: Ixazomib + Dexamethasone | 16.518 | 10.652 | 3.875 | 2.000 | 4.726 | 2.187 | 2.276 | 2.264 | 2.235 | 2.299 | 2.038 | 2.143 | 2.232 |
Time To Subsequent Anticancer Treatment
Time to subsequent anticancer therapy was defined as the time from randomization to the first date of subsequent anticancer therapy. Participants without subsequent anticancer therapy were censored at the date of death or last known to be alive. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until subsequent anticancer treatment (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 26.48 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 12.45 |
Percentage of Participants With Overall Hematologic Response
Overall hematologic response was defined as the percentage of participants with complete response (CR), very good partial response (VGPR) and partial response (PR) based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as assessed by an adjudication committee. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of free light chain (FLC) ratio. VGPR: differential free light chain (difference between involved and uninvolved FLC levels; dFLC) < 40 mg/L. PR: ≥50% reduction in dFLC. Percentages were rounded off to the nearest decimal. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Ixazomib + Dexamethasone | 53 |
| Arm B: Dexamethasone + Melphalan | 58 |
| Arm B: Dexamethasone + Cyclophosphamide | 30 |
| Arm B: Dexamethasone + Thalidomide | 50 |
| Arm B: Dexamethasone + Lenalidomide | 51 |
Percentage of Participants With Complete Hematologic Response
Complete hematologic response was defined as the percentage of participants with CR based on central laboratory results and the 2010 ISA Consensus Criteria as assessed by the investigator. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of FLC ratio. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Ixazomib + Dexamethasone | 30 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 17 |
Time To Treatment Failure (TTF)
TTF was defined as the time from randomization to the date of first documented treatment failure. Treatment failure was defined as: 1) death due to any cause; 2) hematologic progression or major organ progression according to central laboratory results and ISA criteria as evaluated by the investigator; 3) clinically morbid organ disease requiring additional therapy; or 4) withdrawn for any reason. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 10.32 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 5.32 |
Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
Time to vital organ deterioration or death was assessed by the investigator and defined as the time from randomization to vital organ (heart or kidney) deterioration or death, whichever occurs first. Cardiac deterioration is defined as the need for hospitalization for heart failure. Kidney deterioration is defined as progression to ESRD with the need for maintenance dialysis or renal transplantation. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From randomization to time of vital organ deterioration or death (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 38.67 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 26.09 |
Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up
The FACT/GOG-Ntx is a participant completed questionnaire that comprises 11 individual items evaluating symptoms of neurotoxicity on a 5-point scale where: 0=not at all (best) to 4=very much for a total possible score of 0 to 44. Symptom scores are inverted so that higher scores of FACT/GOG-Ntx indicate higher quality of life or functioning. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up
| Intervention | score on a scale (Mean) |
|---|
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 0.0 |
2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
Cardiac (Heart) deterioration was defined as the need for hospitalization for heart failure. Kidney deterioration was defined as progression to end-stage renal disease (ESRD) with the need for maintenance dialysis or renal transplantation. Vital organ deterioration was evaluated by an adjudication committee. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Ixazomib + Dexamethasone | 47 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 54 |
Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up
The amyloidosis symptom scale questionnaire is a participant completed questionnaire that evaluates symptom severity of 3 symptoms: Swelling, Shortness of Breath and Dizziness, each rated on an 11-point scale where: 0=no symptoms to 10=very severe symptoms. Higher scores indicate worsening of symptoms. Total Score is the sum of all responses from the amyloidosis symptom scale ranging from 0 to 30. Higher scores represent higher levels of symptomatology or problems and a negative change from baseline indicates improvement. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up
| Intervention | score on a scale (Mean) |
|---|
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | -16.0 |
Duration of Hematologic Response
Duration of hematologic response (DOR) was defined as the time from the date of first documentation of a hematologic response to the date of first documented hematologic disease progression as determined by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From time of first documented response to disease progression (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | NA |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 21.19 |
EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score
The EQ visual analogue scale (VAS) records the participant's self-rated health on a 20 centimeter vertical VAS that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the value collected at the time closest to, but prior to, the start of study drug administration. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: At Week 28 of the OS follow-up
| Intervention | score on a scale (Mean) |
|---|
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 23.0 |
Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score
The European Quality of Life (EuroQOL) 5-Dimensional (EQ-5D) is a patient completed questionnaire consisting of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 3 possible choices: no problems to extreme problems. Higher scores=worsening of the quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: At Week 28 of the OS follow-up
| Intervention | Participants (Count of Participants) |
|---|
| Mobility: No Problems in Walking About | Mobility: Some Problem in Walking About | Mobility: Confined to Bed | Self-Care: No Problems With Self- Care | Self-Care: Some Problems Washing or Dressing | Self-Care: Unable to Wash or Dress | Usual Activities: No Problems With Performing Usual Activities | Usual Activities: Some Problem With Performing Usual Activities | Usual Activities: Unable to Performing Usual Activities | Pain/Discomfort: No Pain or Discomfort | Pain/Discomfort: Moderate Pain or Discomfort | Pain/Discomfort: Extreme Pain or Discomfort | Anxiety/Depression: Not Anxious or Depressed | Anxiety/Depression: Moderately Anxious or Depressed | Anxiety/Depression: Extremely Anxious or Depressed |
|---|
| Arm A: Ixazomib + Dexamethasone | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
Hematologic Disease Progression Free Survival
Hematologic disease PFS was defined as the time from the date of randomization to the date of first documentation of hematologic PD according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurred first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 29.50 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 27.73 |
Number of Hospitalizations
A hospitalization was defined as at least one overnight stay in an intensive care unit and/or non-intensive care unit. If a single hospitalization included both an intensive care unit stay and a non-intensive care unit stay, the hospitalization was counted only once (as an intensive care unit stay). The mean number of hospitalizations is reported in this outcome measure. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | hospitalizations (Mean) |
|---|
| Arm A: Ixazomib + Dexamethasone | 1.8 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 1.4 |
Number of Participants With Serious Adverse Events (SAEs)
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or medically important event. (NCT01659658)
Timeframe: From first dose of study drug through 30 days after administration of the last dose of study drug (up to 115 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Ixazomib + Dexamethasone | 44 |
| Arm B: Dexamethasone + Melphalan | 11 |
| Arm B: Dexamethasone + Cyclophosphamide | 2 |
| Arm B: Dexamethasone + Thalidomide | 0 |
| Arm B: Dexamethasone + Lenalidomide | 17 |
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 69.55 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 43.17 |
Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response
Vital organ (heart and kidney) response rate was defined as the percentage of participants who achieved vital organ response according to central laboratory results and ISA criteria as evaluated by an adjudication committee. A vital organ response was defined as response of 1 or 2 of the involved vital organs with no change from Baseline in the rest of involved vital organs. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Ixazomib + Dexamethasone | 19 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 12 |
Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up
SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: Baseline, Week 28 of the PFS Follow-up
| Intervention | score on a scale (Mean) |
|---|
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 10.3 |
Vital Organ Progression Free Survival
Vital organ PFS is defined as the time from the date of randomization to the date of first documentation of progression of vital organ (heart or kidney) according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurs first. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 15.77 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 11.01 |
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of hematologic disease progression, or organ (cardiac or renal) progression, or death due to any cause, whichever occurred first according to central laboratory results and ISA criteria as evaluated by the investigator. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure. (NCT01659658)
Timeframe: From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
| Intervention | months (Median) |
|---|
| Arm A: Ixazomib + Dexamethasone | 11.86 |
| Arm B: Dexamethasone + Melphalan/Cyclophosphamide/Thalidomide/Lenalidomide | 7.62 |
Response (Partial Response [PR] or Better) Rate
Percentage of participants with PR or better to treatment per the International Uniform Response Criteria for Multiple Myeloma stringent Complete Response- CR criteria + normal serum free light chain (FLC) ratio + absence of clonal cells in bone marrow (BM) by immunohistochemistry or immunofluorescence CR- Negative immunofixation (IFX) on serum & urine M proteins + <5% plasma cells in BM + disappearance of soft tissue plasmocytomas (STP) very good PR- PR criteria + serum & urine M proteins detectable by IFX but not on electrophoresis or >=90% reduction (RED) in serum M protein & urine M protein <100 g/24 hrs PR- >=50% RED in size of STP, if present at baseline & >=50% RED in plasma cells, if >=30% plasma cells in BM at baseline: & RED in serum M protein of >=50% & in urine M protein of >= 90% or to 200 mg/24hr OR if serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, & involved serum FLC level >= 10 mg/dl at baseline: >= 50% RED in (involved-uninvolved) serum FLC levels (NCT01668719)
Timeframe: Up to 6 years post registration
| Intervention | Percentage of participants (Number) |
|---|
| Arm I (Bortezomib, Lenalidomide, Dexamethasone) | 88 |
| Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) | 83 |
Progression-free Survival
"From date of registration to date of first documentation of progression or death due to any cause.~Per the International Uniform Response Criteria for Multiple Myeloma, progression is defined as >=1 of Serum M protein increase >= 25% from lowest response level, with an absolute increase of >= 0.5g/dL; Urine M protein increase >= 25% from lowest response level, with an absolute increase of >= 200 mg/24 hrs; If participant had serum M protein <1 g/dL, urine M protein <200 mg/24 hrs, and an involved serum free light chain level >= 10mg/dL at baseline: >= 25% increase in the difference between involved and uninvolved serum free light chain level with an absolute increase of >= 10 mg/dL; Bone marrow plasma cell % increase =25% from baseline with the absolute plasma cell % >=10%; New bone lesions or soft tissue plasmocytomas, or definite increase in size of existing bone lesions or soft tissue plasmocytomas; Development of hypercalcemia that can be attributed solely to multiple myeloma" (NCT01668719)
Timeframe: Up to 6 years post registration
| Intervention | months (Median) |
|---|
| Arm I (Bortezomib, Lenalidomide, Dexamethasone) | 33.6 |
| Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) | 31.5 |
Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone
"Assess safety of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone and select the optimal dose of elotuzumab for the Phase II portion from 10mg/kg on each cycle, to 5mg/kg on each cycle MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 1/6 participants. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 3 nausea or diarrhea despite anti-emetic and anti-diarrheal therapy; grade 3 hyperglycemia if symptomatic or glucose level > 300mg/ml despite insulin and/or oral diabetic therapy; grade 4 neutropenia ≥ 7 days or grade 3/4 neutropenia with fever (≥ 38.5 oC); grade 4 thrombocytopenia ≥ 7 days or associated with hemorrhage; delay of treatment with any agent by > 2 weeks due to drug related toxicity.~DLT were graded using the NCI CTCAE version 4.0~Note:~i) the second, lower dose level was not tested as the first dose level was deemed safe ii) 6 participants were evaluable at phase I analysis" (NCT01668719)
Timeframe: time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)
| Intervention | mg/kg (Phase II dosing for elotuzumab) (Number) |
|---|
| Phase I Dose Level 1 (Elotuzumab, 10mg, and Bortezomib, Lenalidomide and Dexamethasone) | 10 |
Overall Survival
From date of registration to date of death due to any cause (NCT01668719)
Timeframe: Up to 6 years post registration
| Intervention | months (Median) |
|---|
| Arm I (Bortezomib, Lenalidomide, Dexamethasone) | NA |
| Arm II (Bortezomib, Lenalidomide, Dexamethasone, Elotuzumab) | 68 |
Number of Participants With Serious and Non-serious Adverse Events
Here is the number of serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01675141)
Timeframe: 37 months and 12 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide Maintenance Therapy for Multiple Myeloma | 11 |
Progression Free Survival (PFS)
PFS is defined as the time from study entry until progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be >10mg/dl. (NCT01675141)
Timeframe: participants were followed for the duration of their treatment, an average of 2 years
| Intervention | months (Median) |
|---|
| Lenalidomide Maintenance Therapy for Multiple Myeloma | NA |
Duration of Response
Duration of response is defined as time from response to disease progression or death. Progression is assessed by the International Myeloma Workshop Consensus Panel Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from baseline or lowest response value in Serum M component, Urine M component, free light chain or bone marrow plasma cell percentage. Lowest response value does not need to be a confirmed value. Serum M-component absolute increase must be ≥0.5 g/dl. The serum M-component increases of ≥1 gm/dl are sufficient to define relapse if starting M-component is ≥5 g/dl. Urine M-component absolute increase must be ≥200mg/24h. Only in patients without measureable serum and urine M-protein levels: the absolute increase in difference between involved and uninvolved free light chain levels must be >10mg/dl. (NCT01675141)
Timeframe: participants were followed for the duration of their treatment, an average of 2 years
| Intervention | Months (Median) |
|---|
| Lenalidomide Maintenance Therapy for Multiple Myeloma | NA |
Time to Response
"Time to response was calculated for the responders as the time from the first dose date to the initial documented response (CR, VGPR or PR).~CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required." (NCT01698801)
Timeframe: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up time was 61.6 weeks.
| Intervention | months (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 1.97 |
Overall Survival (OS)
The time from the start of study treatment to death due to any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT01698801)
Timeframe: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow up is 14.2 months
| Intervention | months (Median) |
|---|
| Lenalidomide Plus Dexamethasone | 17.71 |
Duration of Response
Duration of response was calculated for the responders as the time from the initial documented response (CR or VGPR or PR) to the first documented progression or death due to any cause, whichever occurred first. Duration of response for participants last known to be alive with no progression after a CR, VGPR, or PR were censored at the date of last adequate response assessment. (NCT01698801)
Timeframe: From the first dose of study drug treatment until the data cut-off date of 15 July2014. Median follow up time was 61.6 weeks.
| Intervention | months (Median) |
|---|
| Lenalidomide Plus Dexamethasone | NA |
Overall Response Rate
"Number of Complete Responses (CR) plus Very Good Partial Response (VGPR) plus Partial Response (PR) based on the International Myeloma Working Group criteria (IMWG). Any participant who achieved a CR, VGPR, or PR while on study treatment was defined as a responder.~CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required." (NCT01698801)
Timeframe: From first dose until the data cut-off date of 15 July 2014. Median time on follow-up was 61.6 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide Plus Dexamethasone | 87.5 |
Number of Participants With Adverse Events
An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death. (NCT01698801)
Timeframe: From first dose of study drug treatment through to 28 days after the last dose, until the data cut-off date of 15 July 2014; median treatment duration was 60 weeks
| Intervention | participants (Number) |
|---|
| Any adverse event | TEAE related to study drug | TEAE related to Lenalidomide | TEAE related to Dexamethasone | Grade 3-4 adverse event | Grade 3-4 adverse event related to any study drug | Grade 3-4 adverse event related to Lenalidomide | Grade 3-4 adverse event related to Dexamethasone | Serious TEAE | Serious TEAE related to any study drug | Serious TEAE related to Lenalidomide | Serious TEAE related to Dexamethasone | TEAE leading to discontinuation of either drug | TEAE leading to discontinuation of lenalidomide | TEAE leading to discontinuation of dexamethasone | Related TEAE discontinuation of either drug | Related TEAE discontinuation of lenalidomide | Related TEAE discontinuation of dexamethasone |
|---|
| Lenalidomide Plus Dexamethasone | 26 | 25 | 25 | 20 | 18 | 15 | 15 | 4 | 11 | 8 | 8 | 3 | 4 | 4 | 2 | 4 | 4 | 0 |
Progression Free Survival (PFS)
PFS was calculated as the time from the first dose date to the first documented progression based on IWG criteria or death due to any cause, whichever occurred first. If progression or death was not documented at the time of data cutoff date, these observations were censored at the last adequate assessment date showing evidence of no progression or death. (NCT01698801)
Timeframe: From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up for PFS assessments was 61.6 weeks.
| Intervention | months (Median) |
|---|
| Lenalidomide Plus Dexamethasone | NA |
Part A and B: Safety and Tolerability
(NCT01704781)
Timeframe: Part A: 31 days and Part B: 26 weeks
| Intervention | participants (Number) |
|---|
| With any TEAE | With TESAE | With any AE resultiung in withdrawal | Deaths |
|---|
| Part A: Lenalidomide 10 mg | 2 | 0 | 0 | 0 |
,| Part A: Lenalidomide 5 mg | 3 | 0 | 0 | 0 |
,| Part A: Lenalidopmide 25 mg | 6 | 0 | 0 | 0 |
,| Part B: Lenalidomide | 10 | 1 | 0 | 0 |
,| Part B: Lenalidomide Placebo | 9 | 0 | 0 | 0 |
Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time
(NCT01704781)
Timeframe: 31 days
| Intervention | 10^6 cells/mL (Mean) |
|---|
| Baseline | Week 1 | Week 4 | Week 5 |
|---|
| Part A: Lenalidomide 10 mg | 436.3 | 317.0 | 399.3 | 449.0 |
,| Part A: Lenalidomide 5 mg | 437.3 | 393.0 | 442.0 | 432.7 |
,| Part A: Lenalidopmide 25 mg | 454.2 | 342.2 | 450.7 | 452.3 |
Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity
Number of participants in each of the three groups that experienced any dose-limiting toxicity. (NCT01704781)
Timeframe: 31 days
| Intervention | Participants (Count of Participants) |
|---|
| Part A: Lenalidomide 5 mg | 0 |
| Part A: Lenalidomide 10 mg | 0 |
| Part A: Lenalidopmide 25 mg | 0 |
Part B: Incidents of Delayed-type Hypersensitivity
Delayed-type hypersensitivity measured by induration and erythema. (NCT01704781)
Timeframe: 26 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Week 1, Induration | Week 1, Erythema | Week 26, Induration | Week 26, Erythema |
|---|
| Part B: Lenalidomide | 0 | 0 | 5 | 6 |
,| Part B: Lenalidomide Placebo | 0 | 1 | 2 | 6 |
Part B: Evaluate the Effect on HIV Viral Load
Results BLQ (<20 HIV copies/mL) have been replaced with BLQ/2 = 10 HIV copies/mL while 'not detected' results have been replaced with 0 HIV copies/mL. (NCT01704781)
Timeframe: 26 weeks
| Intervention | Copies/mL (Mean) |
|---|
| Baseline | Week 1 | Week 4 | Week 12 | Week 13 | Week 21 | Week 26 |
|---|
| Part B: Lenalidomide | 0.8 | 5.1 | 6.4 | 5.5 | 7.4 | 1.7 | 3.5 |
,| Part B: Lenalidomide Placebo | 2.5 | 0.0 | 0.9 | 4.3 | 1.7 | 4.2 | 2.5 |
Part B: Change in CD8 Count
Change in CD8 count from baseline to week 26. (NCT01704781)
Timeframe: 26 weeks
| Intervention | 10^6 cells/L (Mean) |
|---|
| Baseline | Week 1 | Week 4 | Week 12 | Week 13 |
|---|
| Part B: Lenalidomide | 734.2 | 653.8 | 744.9 | 823.0 | 811.2 |
,| Part B: Lenalidomide Placebo | 655.3 | 784.5 | 794.5 | 760.3 | 663.6 |
Part B: Change in CD4 Count
Change in CD4 count from baseline to Week 26. (NCT01704781)
Timeframe: Week 26
| Intervention | 10^6 cells/L (Mean) |
|---|
| ITT | PP |
|---|
| Part B: Lenalidomide | 90.9 | 106.3 |
,| Part B: Lenalidomide Placebo | 42.2 | 49.1 |
Survival Time
The distribution of survival time will be estimated by arm using the method of Kaplan-Meier. (NCT01706666)
Timeframe: From registration to death due to any cause, assessed up to 3 years
| Intervention | Months to death (Number) |
|---|
| Arm A | NA |
| Arm B | NA |
| Arm C | NA |
Proportion of Patients Experiencing a Stringent Complete Response (sCR) After 12 Cycles, 24 Months
Estimated by the number of sCRs divided by the total number of evaluable patients in each arm. Exact binomial confidence intervals for the true sCR rate will be calculated by arm. Stringent complete response (sCR) is defined as a complete response plus normal serum free light chain ratio and the absence of clonal cells in bone marrow by flow cytometry. (NCT01706666)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| Arm A | 100 |
| Arm B | 0 |
| Arm C | 100 |
Progression-free Survival
The distribution of progression-free survival will be estimated by arm using the method of Kaplan-Meier. (NCT01706666)
Timeframe: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years
| Intervention | Months to Progression (Number) |
|---|
| Arm A | NA |
| Arm B | 9.2 |
| Arm C | NA |
Overall Response Rate
Analysis of the other Secondary Endpoints: The overall response rate will be estimated by the number of patients with complete and partial responses divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 6 cycles
| Intervention | Percentage of Participants (Number) |
|---|
| FCR With Lenalidomide | 95 |
Complete Response
Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 4 cycles
| Intervention | Percentage of Participants (Number) |
|---|
| FCR With Lenalidomide | 45 |
Time to Response
Time to Response was defined as the time from the first dose of study treatment to the initial documented response (CR or CRu, or PR) (NCT01724177)
Timeframe: From day 1 of study treatment to first documented response; up to data cut-off date of 19 May 2017; maximum study duration was 134.1 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 8.10 |
Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response (CRu), Partial Response or Stable Disease (SD) as Assessed by the ESEC
The tumor control rate was measured for those with a response of Complete Remission, + CRu, + PR + Stable Disease (SD) in the EE population based on the best response. (NCT01724177)
Timeframe: From day 1 of study treatment to first documented response; up to data cut-off date of 19 May 2017; maximum study duration was 134.1 weeks
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 73.1 |
Kaplan-Meier Estimate of Duration of Response (DOR) for Responders as Assessed by the ESEC
The response duration in participants with an objective response was measured from the date of the first Complete Response or Complete Response unconfirmed or Partial Response to the first date of Relapsed Disease or Progressive Disease (PD). For participants who did not progress during the study, DOR was censored at the last adequate response assessment not showing evidence of PD. (NCT01724177)
Timeframe: From day 1 of study treatment to first documented response; up to data cut-off date of 19 May 2017; Maximum study duration was 134.1 Weeks
| Intervention | weeks (Number) |
|---|
| Lenalidomide | 24.10 |
Kaplan-Meier Estimate for Overall Survival
Overall Survival was defined as the time from the start of study treatment to the death due to any cause. For participants who were still alive at the time of the data cutoff, survival data were censored at the latest available date the participant was known to be alive. (NCT01724177)
Timeframe: From Day 1 of study treatment to disease progression or death; up to final data cut-off date of 19 May 2017; maximum surivival time was 197.9 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 88.10 |
Number of Participants With Treatment Emergent Adverse Events
Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the start of study treatment and within 28 days after the last dose. Severity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): Grade 1= Mild Grade 2= Moderate Grade 3= Severe Grade 4= Life-threatening and Grade 5= Death related to AE. Serious AEs (SAEs) were those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. (NCT01724177)
Timeframe: From the date of the first dose of study drug up to 28 days after the last dose of study drug; up to data cutoff date of 19 May 2017; maximum treatment duration was 130.1 weeks
| Intervention | participants (Number) |
|---|
| ≥ 1 TEAE | ≥ 1 TEAE Related to Lenalidomide | ≥ 1 NCI CTCAE Grade (GR) 3 or Greater TEAE | ≥ 1 NCI CTCAE ≥ GR 3 TEAE Related to Lenalidomide | ≥ 1 Serious TEAE | ≥ 1 Serious TEAE Related to Lenalidomide | ≥ 1 TEAE Leading to Discontinuation | ≥ 1 Related TEAE Leading to Discontinuation | ≥ 1 TEAE Leading to Dose Reduction/Interruption | ≥ 1 related TEAE Leading to Decrease/Interruption | ≥ 1 TEAE Resulting in Death |
|---|
| Lenalidomide | 26 | 26 | 25 | 25 | 11 | 9 | 8 | 8 | 17 | 17 | 0 |
Kaplan Meier Estimate of Progression Free Survival (PFS) as Assessed by the ESEC
PFS was defined as the time from the first dose of study treatment to progressive disease (PD) or death due to any cause on study or within 28 days after study discontinuation, whichever occurred earlier. (NCT01724177)
Timeframe: From day 1 of study treatment to the date of disease progression; up to data cut date of date of 19 May 2017; maximum study duration was 134.1 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 16.30 |
Percentage of Participants Who Achieved a Complete Response, Unconfirmed Complete Response, or Partial Response as Assessed by the Efficacy-Safety Evaluation Committee (ESEC)
"ORR is a Complete Response (CR) + Complete Response unconfirmed (CRu) + Partial Response (PR). A CR requires that target lesions have regressed to normal; nodal non-target lesions have regressed to normal; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are GR 0; peripheral blood is normal; Bone marrow (BM) infiltration is negative and no new lesions. A CRu requires the sum of the product diameters (SPD) of target lesions have decreased by at least 75% from baseline; nodal non-target lesions have regressed to normal size; extranodal non-target lesions have disappeared; hepatomegaly/splenomegaly has disappeared; skin findings are Grade 0; peripheral blood is normal; BM infiltration is negative and no new lesions. A PR requires the SPD of target lesions has decreased by at least 50% from baseline; all nodal non-target lesions have regressed to normal or show no increase in size; all extranodal non-target lesions have disappeared" (NCT01724177)
Timeframe: From day 1 of study treatment to date of first documented CR, CRU or PR; Up to data cut-off date of 19 May 2017; maximum study duration was 134.1 weeks
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide | 42.3 |
Kaplan-Meier Estimate of Time to Progression (TTP)
Time to progression was calculated as the time from the first dosing of study treatment to the first documented PD and assessed by the ESEC (NCT01724177)
Timeframe: From day 1 of study treatment to the date of disease progression; up to data cut date of 19 May 2017; maximum study duration was 134.1 weeks
| Intervention | weeks (Median) |
|---|
| Lenalidomide | 16.30 |
QLQ-C30 Question 30
"Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 30: How would you rate your overall quality of life during the past week?~7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality." (NCT01729338)
Timeframe: baseline, 3 months, 5 months
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 3 months | 5 months |
|---|
| Velcade, Cyclophosphamide, Revlimid | 51.7 | 66.7 | 66.7 |
Overall Response Rate (ORR) During Induction Therapy
"Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria:~IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour." (NCT01729338)
Timeframe: Up to 8 months
| Intervention | percentage of participants (Number) |
|---|
| Velcade, Cyclophosphamide, Revlimid | 64 |
QLQ-C30 Question 29
Measured as mean quality of life in study subjects, quantitatively scored using the standardized and validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Question 29: how would you rate your overall health during the past week? 7 point scores are standardized to a scale of 0-100, where 100 means highest possible quality. (NCT01729338)
Timeframe: baseline, 3 months, 5 months
| Intervention | units on a scale (Mean) |
|---|
| Baseline | 3 months | 5 months |
|---|
| Velcade, Cyclophosphamide, Revlimid | 58.3 | 65 | 68.3 |
Severe Adverse Event Rate
Defined as number of patients experiencing any grade or severe (≥ grade 3 by common toxicity criteria for adverse events (CTCAE) v4.0 criteria) adverse events at any time during the study (NCT01729338)
Timeframe: Up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| Velcade, Cyclophosphamide, Revlimid | 64 |
Maximum Depth of Response During Induction Therapy
Maximum depth of response is defined as: ranging from partial response to complete response by International Myeloma Working Group (IMWG). Described as number of patients achieving each level of response. IMWG: CR: negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; sCR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; PR: ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease. (NCT01729338)
Timeframe: Up to 8 months
| Intervention | percentage of participants (Number) |
|---|
| Stable Disease | Partial Response | Very good partial response (VGPR) | Complete Response/Stringent complete response | Progressive Disease/no response |
|---|
| Velcade, Cyclophosphamide, Revlimid | 21 | 7 | 29 | 29 | 14 |
Maximum Depth of Response During Maintenance Therapy
"Defined as maximum depth of response (ranging from partial response to complete response by International Myeloma Working Group (IMWG) criteria at any point during post-induction maintenance therapy.~IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and <5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, >90% in serum M-protein+urine, M-protein level <100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or <200 mg/24hour. Stable disease mean that the patient has not achieved CR, VGPR, PR or progressive disease." (NCT01729338)
Timeframe: Up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| Stable Disease | Partial Response | Very good partial response | Complete Response/Stringent complete response | Progressive Disease/no response |
|---|
| Velcade, Cyclophosphamide, Revlimid | 13 | 0 | 50 | 38 | 0 |
Overall Survival Rate (OS)
To compare overall survival in subjects receiving autologous peripheral blood stem cell transplant after undergoing induction therapy with lenalidomide and dexamethasone versus in those receiving only lenalidomide and dexamethasone, followed by lenalidomide maintenance in both arms. Only patients who achieved at least a partial response (PR) following 4 cycles of induction were included in the analysis. (NCT01731886)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Low-dose Dexamethasone + Stem Cell Transplantation | 100 |
| Arm B: Low-dose Dexamethasone | 94.7 |
Overall Survival Rate (OS)
To compare overall survival in subjects receiving autologous peripheral blood stem cell transplant after undergoing induction therapy with lenalidomide and dexamethasone versus in those receiving only lenalidomide and dexamethasone, followed by lenalidomide maintenance in both arms. Only patients who achieved at least a partial response (PR) following 4 cycles of induction were included in the analysis. (NCT01731886)
Timeframe: 4 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Low-dose Dexamethasone + Stem Cell Transplantation | 79.8 |
| Arm B: Low-dose Dexamethasone | 78.9 |
Progression Free Survival (PFS)
PFS is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. (NCT01731886)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Low-dose Dexamethasone + Stem Cell Transplantation | 52.0 |
| Arm B: Low-dose Dexamethasone | 47.4 |
Progression Free Survival (PFS)
PFS is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. (NCT01731886)
Timeframe: 4 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Low-dose Dexamethasone + Stem Cell Transplantation | 36.0 |
| Arm B: Low-dose Dexamethasone | 31.6 |
Complete Response Rate
The primary objective of this study is to determine the complete response rate of lenalidomide and low-dose dexamethasone versus that of lenalidomide and low-dose dexamethasone followed by autologous peripheral blood stem cell transplant in patients with newly diagnosed multiple myeloma (will include unconfirmed complete response (CR), CR and stringent complete response (sCR)). (NCT01731886)
Timeframe: 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Low-dose Dexamethasone + Stem Cell Transplantation | 7 |
| Arm B: Low-dose Dexamethasone | 7 |
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT01743859)
Timeframe: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)
| Intervention | percentage of participants (Number) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 11 |
Progression-free Survival
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination (NCT01743859)
Timeframe: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
| Intervention | days (Median) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 112 |
Response or Remission Duration
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination (NCT01743859)
Timeframe: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
| Intervention | days (Median) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 125 |
Determine Biomarkers That Predict Response/Toxicity
Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers. Computational biology modeling used to identify biomarkers and predict response. (NCT01743859)
Timeframe: Three years after initiating study
| Intervention | patients w/response predictor mutations (Number) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 9 |
Overall Response Rate
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination (NCT01743859)
Timeframe: Planned assessment after enrollment of all 37 patients (estimated 3-4 years)
| Intervention | percentage of participants (Number) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 52 |
Overall Survival
Change in baseline to end of study (NCT01743859)
Timeframe: Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years
| Intervention | days (Median) |
|---|
| Azacitidine + Lenalidomide + Off Therapy | 166 |
Time to Progression
The primary objective is progression-free survival (PFS). Tumor measurements and disease assessments will be performed at the time of screening, following cycles 3 and 6 of induction chemotherapy, every 4 cycles during the maintenance portion of treatment, and at the end of treatment (EOT). Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression. Follow-up visits for disease assessment will occur every 3 months after the EOT visit until PD, initiation of alternate anti-neoplastic therapy, decision by the subject to withdraw from the study, or death. The follow-up period will begin after the EOT visit, and all subjects will be followed for at least 2 years after completion of therapy or until death or progression and until the last patient has been followed for at least 1 year following completion of therapy. (NCT01754857)
Timeframe: At least 24 months following completion of therapy, an average of 5 years
| Intervention | years (Median) |
|---|
| Bendamustine, Rituximab, Lenalidomide | 4.76 |
Number of Patients With Hematologic Improvement in Platelet Counts (HI-P)
The Number of Patients with Hematologic Improvement in Platelet Counts (HI-P) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an absolute increase of ≥ 30 × 10^9/L (for those patients starting with > 20 × 10^9/L platelets) or an increase from < 20 × 10^9/L to > 20 × 10^9/L along with an increase of at least 100%, were deemed to have demonstrated HI-P improvement. (NCT01772420)
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 0 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 3 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 6 |
Number of Patients With Clinically Significant Bleeding Events
Number of Patients With Clinically Significant Bleeding Events (NCT01772420)
Timeframe: Treatment initiation through study completion, up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 0 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 2 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 0 |
Number of Patients With Hematologic Improvement in Neutrophil Counts (HI-N)
The Number of Patients with Hematologic Improvement in Neutrophil Counts (HI-N) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an increase of at least 100% and an absolute increase > 0.5 × 10^9/L were determined to have shown an improvement in HI-N. (NCT01772420)
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 0 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 1 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 2 |
Number of Patients Demonstrating Overall Hematologic Improvement (HI)
The number of patients demonstrating overall Hematologic Improvement (HI) was assessed based on the MDS 2006 IWG criteria. The IWG criteria for HI define specific responses of cytopenia in the 3 hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N) as demonstrated in corresponding outcome measures. Responses must have sustained for at minimum of 8 weeks for the participant to be included in the tally. (NCT01772420)
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 6 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 5 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 7 |
Duration of Hematologic Improvement (HI)
Duration to hematologic improvement as determined by median duration of HI response. (NCT01772420)
Timeframe: Time to progression/relapse following hematologic improvement, at completion of final cycle and treatment discontinuation; up to 6 years
| Intervention | number of weeks (Median) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 41 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 88 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 40 |
Time to Attain Hematologic Improvement (HI)
Time to hematologic improvement as determined by median time required to achieve HI response. (NCT01772420)
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
| Intervention | number of weeks (Median) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 12 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 8 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 8 |
Number of Patients With Hematologic Improvement in Erythrocyte Counts (HI-E)
The Number of Patients with Hematologic Improvement in Erythrocyte Counts (HI-E) was assessed based on the MDS 2006 IWG criteria. Patients demonstrating an Hgb increase by ≥ 1.5 g/dL were deemed to have improvement in HI-E. Only transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response. (NCT01772420)
Timeframe: Periodic evaluation (weekly up to a month, followed by 4x28 day cycles = 16weeks) with additional cycles and titrations depending upon treatment response; up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Platelets > 50,000 k/uL) LEN Initiation | 6 |
| Arm B (Platelets < 50,000 k/uL) ELT Initiation With Potential LEN Combination | 3 |
| Arm C (Platelets < 50,000 k/uL) ELT Monotherapy | 4 |
Number of Patients Who Demonstrate a Response (Complete, Partial, Minor) to Treatment
"Response criteria for subjects with WM is based upon the Consensus Panel Recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.~Overall response rate (CR + PR + MR) measured at time of best response." (NCT01779167)
Timeframe: Approximately 24 months
| Intervention | participants (Number) |
|---|
| All Patients | 0 |
Mean Plasma Bortezomib Concentration Following Intravenous and and Subcutaneous Injection
The pharmacokinetic profile of intravenous and subcutaneous bortezomib administration in combination with lenalidomide and dexamethasone. (NCT01782963)
Timeframe: Day 1 (5 min, 30min, 5 hours post dose), Days 8, 15, Day 22 (pre dose and 5 min, 30 min, 5 hrs post dose), cycle 2 day 1 pre dose
| Intervention | ng/mL (Mean) |
|---|
| Day 1, 5 minutes (min) post dose | Day 1, 30 min post dose | Day 1, 5 hours post dose | Day 8 pre-dose | Day 15 pre-dose | Day 22 pre-dose | Day 22, 5 min post-dose | Day 22, 30 min post-dose | Day 22, 5 hours post-dose | Cycle 2 Day 1, pre-dose |
|---|
| Intravenous | 98.84 | 8.73 | 1.82 | 0.44 | 0.66 | 0.83 | 114.3 | 14.9 | 2.85 | 0.53 |
,| Subcutaneous | 13 | 20.5 | 1.96 | 0.33 | 0.49 | 0.66 | 10.29 | 21.69 | 4.16 | 0.49 |
Objective Response Rate
"Participants are considered to have achieved an objective response if they meet the International Myeloma Working Group uniform response criteria for any of the following:~Stringent CR: Same as CR plus normal free light chain ratio and absence of clonal cells plasma cells in bone marrow (BM)~CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM~VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours~PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 hours. If the serum and urinary M-protein are not measurable, additional criteria are used to assess PR that will not fit in the space provided here. If present at baseline, a ≥50% reduction in the size of plasmacytomas is also required" (NCT01782963)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Stringent Complete Response | Complete Response (CR) | Very Good Partial Response (VGPR) | Partial Response (PR) |
|---|
| Treatment Arm | 6 | 16 | 11 | 10 |
Proportion of Confirmed Tumor Responses Defined to be a Partial Response or Better Noted as the Objective Status on Two Consecutive Evaluations
The proportion of successes will be estimated in each arm independently by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. A confirmed tumor response is defined to be a partial response or better noted as the objective status on two consecutive evaluations while receiving lenalidomide and dexmethasone (Arm A) or pomalidomide and dexamethasone (Arm B). All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. (NCT01794039)
Timeframe: Up to 2 years
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Lenalidomide, Dexamethasone) | .4 |
| Arm B (Pomalidomide, Dexamethasone) | .25 |
Time to Progression
The distribution of time to progression will be estimated using the method of Kaplan-Meier. The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. (NCT01794039)
Timeframe: Time from registration to the earliest date with documentation of disease progression, assessed up to 2 years
| Intervention | Months (Median) |
|---|
| Arms A and B | 10 |
Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Recorded and reported for each patient, and frequency tables will be reviewed to determine adverse event patterns. These results are reported in the Adverse Events section of this CT.gov report. (NCT01794039)
Timeframe: Up to 30 days after last day of study drug treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Lenalidomide, Dexamethasone) | 5 |
| Arm B (Pomalidomide, Dexamethasone) | 4 |
Overall Survival
The distribution of survival time will be estimated using the method of Kaplan-Meier. Due to an early closer from slow accrual the data from both arms was combined in survival analysis. (NCT01794039)
Timeframe: Time from registration to death due to any cause, assessed up to 2 years
| Intervention | Months (Median) |
|---|
| Arms A and B | 13.4 |
Percentage of Participants With Progression-free Survival (PFS)
Progression-free Survival rate was estimated at months 12, 24, 36, 48, and 60, by the product-limit method of Kaplan and Meier. (NCT01816971)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| PFS rate at 12 months (%) | PFS rate at 24 months(%) | PFS rate at 36 months(%) | PFS rate at 48 months(%) | PFS rate at 60 months(%) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | 97 | 93 | 80 | 76 | 72 |
Percentage of Participants With Overall Survival (OS)
Overall survival rate was estimated at months 12, 24, 36, 48, and 60, by the product-limit method of Kaplan and Meier. (NCT01816971)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| OS rate at 12 months (%) | OS rate at 24 months (%) | OS rate at 36 months (%) | OS rate at 48 months (%) | OS rate at 60 months (%) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | 100 | 97 | 96 | 93 | 84 |
Time to Progression
Estimated using the product-limit method of Kaplan and Meier. (NCT01816971)
Timeframe: Up to 5 years
| Intervention | month (Median) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | NA |
Percentage of Patients Achieving sCR
The percentage of stringent complete response (CR) (sCR) will be reported along with 95% confidence intervals, adjusted for the two-stage nature of the trial design. (NCT01816971)
Timeframe: Day 224
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | 76 |
Overall Response Rate, Defined as at Least a Partial Response to Therapy (> PR), at Least Very Good Partial Response (VGPR) and at Least Near Complete Response (nCR) Rate
Reported along with its exact 95% binomial confidence interval. (NCT01816971)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | 97 |
Duration of Response
Reported along with its exact 95% binomial confidence interval. Estimated using the product-limit method of Kaplan and Meier. (NCT01816971)
Timeframe: Up to 5 years
| Intervention | month (Median) |
|---|
| Treatment (Dexamethasone, Carfilzomib, Lenalidomide) | NA |
Cmax: Maximum Plasma Concentration for Ixazomib
(NCT01850524)
Timeframe: Cycle 1 Day 1: Post-dose at multiple timepoints up to 4 hours; Pre-dose at Cycle 1 Day 14, Cycles 2-3 Day 1 and Day 14, Cycles 4-11 Day 1 (Each cycle length = 28 days)
| Intervention | nanograms per milliliter (Mean) |
|---|
| Cycle 1 Day 1: 1 Hour Post-dose | Cycle 1 Day 1: 4 Hours Post-dose | Cycle 1 Day 14: Pre-dose | Cycle 2 Day 1: Pre-dose | Cycle 2 Day 14: Pre-dose | Cycle 3 Day 1: Pre-dose | Cycle 3 Day 14: Pre-dose | Cycle 4 Day 1: Pre-dose | Cycle 5 Day 1: Pre-dose | Cycle 6 Day 1: Pre-dose | Cycle 7 Day 1: Pre-dose | Cycle 8 Day 1: Pre-dose | Cycle 9 Day 1: Pre-dose | Cycle 10 Day 1: Pre-dose | Cycle 11 Day 1: Pre-dose | Cycle 12 Day 1: Pre-dose |
|---|
| Ixazomib | 44.745 | 16.253 | 7.867 | 2.664 | 8.521 | 2.763 | 8.490 | 3.284 | 3.594 | 2.603 | 2.598 | 2.539 | 2.593 | 2.536 | 2.667 | 2.686 |
Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
The laboratory values assessment included serum chemistry and hematology. The Serum chemistry assessment included blood urea nitrogen (BUN), creatinine, bilirubin (total), urate, lactate dehydrogenase, phosphate, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, sodium, potassium, calcium, chloride, carbon dioxide (CO2), magnesium, thyroid stimulating hormone (TSH). Hematology assessment included hemoglobin, hematocrit, platelet (count), leukocytes with differential neutrophils (ANC). Participants with abnormal serum chemistry laboratory values reported as TEAEs are reported. TEAEs were defined as events that occurred after administration of the first dose of any agent in the study drug regimen and through 30 days after the last dose of any agent in the study drug regimen. (NCT01850524)
Timeframe: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)
| Intervention | Participants (Count of Participants) |
|---|
| Hypokalaemia | Blood creatinine increased | Hypophosphataemia | Hypomagnesaemia | Hyponatraemia | Hyperglycaemia | Hypocalcaemia | Hyperkalaemia | Alanine aminotransferase increased | Iron deficiency | Hypercalcaemia | Creatinine renal clearance decreased | Hypoalbuminaemia | Aspartate aminotransferase increased | Hyperuricaemia | Anaemia | Thrombocytopenia | Neutropenia | Neutrophil count decreased | Platelet count decreased | Lymphopenia | Febrile neutropenia | Leukopenia | International normalised ratio increased | Pancytopenia | Iron deficiency anaemia | White blood cell count decreased | Lymphocyte count decreased |
|---|
| Ixazomib + LenDex (Exposure ≥19 Cycles) | 39 | 16 | 9 | 15 | 7 | 6 | 4 | 3 | 10 | 7 | 5 | 4 | 3 | 5 | 2 | 58 | 24 | 39 | 18 | 15 | 4 | 2 | 2 | 4 | 2 | 4 | 2 | 0 |
,| Ixazomib+ LenDex (Exposure Up to 18 Cycles) | 33 | 6 | 9 | 6 | 10 | 7 | 6 | 7 | 1 | 1 | 2 | 1 | 2 | 0 | 2 | 53 | 34 | 15 | 5 | 6 | 7 | 7 | 6 | 4 | 3 | 1 | 1 | 2 |
,| Placebo + LenDex (Exposure ≥19 Cycles) | 33 | 12 | 3 | 11 | 8 | 16 | 12 | 3 | 4 | 2 | 1 | 7 | 1 | 3 | 1 | 52 | 14 | 48 | 13 | 4 | 2 | 2 | 4 | 0 | 1 | 1 | 3 | 3 |
,| Placebo + LenDex (Exposure Up to 18 Cycles) | 16 | 9 | 2 | 8 | 7 | 4 | 13 | 3 | 1 | 2 | 6 | 2 | 5 | 1 | 2 | 57 | 15 | 36 | 11 | 6 | 0 | 5 | 3 | 1 | 2 | 1 | 5 | 1 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. (NCT01850524)
Timeframe: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs |
|---|
| Ixazomib + LenDex (Exposure ≥19 Cycles) | 191 | 125 |
,| Ixazomib+ LenDex (Exposure Up to 18 Cycles) | 163 | 119 |
,| Placebo + LenDex (Exposure ≥19 Cycles) | 189 | 119 |
,| Placebo + LenDex (Exposure Up to 18 Cycles) | 160 | 105 |
Time to Response
Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 1.87 |
| Ixazomib + LenDex | 1.02 |
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis are censored at the date last known to be alive. (NCT01850524)
Timeframe: From the date of randomization to death due to any cause (Up to approximately 9 years)
| Intervention | months (Median) |
|---|
| Placebo + LenDex | NA |
| Ixazomib + LenDex | NA |
Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR + partial response (PR) + very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and <5 % PC's in bone marrow. PR was defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% along with ≥50% reduction in the size of soft tissue plasmacytomas. VGPR was defined as ≥90% in serum M-component plus urine M-component <100 mg/24. sCR is defined as stringent complete response. Percentages are rounded off to nearest whole numbers. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | percentage of participants (Number) |
|---|
| Placebo + LenDex | 80 |
| Ixazomib + LenDex | 82 |
OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
OS was defined as the time from the date of randomization to the date of death, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. High risk category includes t(4;14), t(14;16), or del(17) abnormalities. (NCT01850524)
Timeframe: From the date of randomization to death due to any cause (Up to approximately 9 years)
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 43.1 |
| Ixazomib + LenDex | 39.0 |
Duration of Response
Duration of response was measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 37.5 |
| Ixazomib + LenDex | 50.6 |
Complete Response (CR) Rate
CR rate was defined as the percentage of participants who achieve CR assessed by an IRC relative to the intent-to-treat (ITT) population during the treatment period. Percentage of participants with CR, as assessed by IMWG disease assessment criteria were reported. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and <5 % plasma cells (PC's) in bone marrow. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | percentage of participants (Number) |
|---|
| Placebo + LenDex | 14 |
| Ixazomib + LenDex | 26 |
Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
The absence of minimal residual disease (MRD negativity) was tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates. (NCT01850524)
Timeframe: Up to Cycle 18 (cycle length = 28 days)
| Intervention | percentage of participants (Number) |
|---|
| Placebo + LenDex | 50 |
| Ixazomib + LenDex | 59 |
PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 17.5 |
| Ixazomib + LenDex | 22.4 |
Time to Progression (TTP)
Time to progression was defined as the time from randomization to the date of first documented disease progression. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 26.8 |
| Ixazomib + LenDex | 45.8 |
Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
EORTC QLQ-MY20 was a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Subscale and individual items include future perspective items 18-20, body image item 17, disease symptoms items 1-6, side effects of treatment items 7-16. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life. Positive change indicates improvement. (NCT01850524)
Timeframe: Baseline to approximately 9 years
| Intervention | score on a scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: End of Treatment | Side-Effects: Baseline | Side-Effects: End of Treatment | Body Image: Baseline | Body Image: End of Treatment | Future Perspective: Baseline | Future Perspective: End of Treatment |
|---|
| Ixazomib + LenDex | 29.2 | -5.3 | 17.6 | 3.3 | 81.2 | -2.3 | 55.0 | 6.0 |
,| Placebo + LenDex | 30.3 | -3.1 | 18.0 | 1.7 | 81.7 | -7.8 | 57.3 | 4.4 |
Time to Pain Progression
Time to pain progression was assessed as the time from randomization to the date of initial progression classification. Pain progression was defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score > 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 47.1 |
| Ixazomib + LenDex | NA |
Progression Free Survival (PFS)-2
PFS2 was defined as the time from the date of randomization to the date of documentation of disease progression on the subsequent line of anticancer therapy, as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first. (NCT01850524)
Timeframe: Up to approximately 9 years
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 52.2 |
| Ixazomib + LenDex | 63.2 |
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause according to International Myeloma Working Group (IMWG) criteria whichever occurs first. PD required one of the following: Increase of >=25% from nadir in: Serum M-component and/or (the absolute increase must be >=0.5 g/dL); Urine M-component and/or (the absolute increase must be >=200 mg/24 hours); in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dL); Bone marrow plasma cell percentage: the absolute % must be >10%; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.85 mmol/L). (NCT01850524)
Timeframe: Up to approximately 79 months
| Intervention | months (Median) |
|---|
| Placebo + LenDex | 21.8 |
| Ixazomib + LenDex | 35.3 |
Proportion of Patients With Response
"Response is defined as complete response (CR) or partial response (PR) CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms~PR:~>=50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses~No increase in the size of other nodes, liver or spleen~Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified~No new sites of disease~The post-treatment PET should be positive at any previously involved sites~For variably FDG-avid lymphomas/FDG-avidity unknown, without a pretreatment PET scan, or if a pretreatment PET scan was negative, CT scan criteria should be used~Patients with a CR and persistent morphologic bone marrow involvement~Patients with bone marrow involved before therapy and a clinical CR but no bone marrow assessment after treatment" (NCT01856192)
Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10
| Intervention | proportion of participants (Number) |
|---|
| Arm A (R2CHOP) | 0.97 |
| Arm B (RCHOP) | 0.92 |
3-year Progression-free Survival Rate
"Progression-free survival is defined as the time from randomization to disease progression, new primary of the same type or death, whichever occurs first. Progressive disease is defined as:~Appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size.~>= 50% increase from nadir in the sum of the product of the diameters of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions.~>= 50% increase in the longest diameter of any single previously identified node or extranodal mass > 1 cm in its short axis.~Lesions should be PET positive unless the lesion is too small to be detected with current PET systems.~Measurable extranodal disease should be assessed in a manner similar to that for nodal disease.~3-year progression-free survival rate was calculated using Kaplan-Meier method." (NCT01856192)
Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10, 3-year PFS rate reported
| Intervention | proportion of participants (Number) |
|---|
| Arm A (R2CHOP) | 0.727 |
| Arm B (RCHOP) | 0.615 |
Overall Survival Rate at 3 Years
Overall survival is defined as time from randomization to death or date last known alive. Overall survival rate at 3 years was calculated using the method of Kaplan Meier. (NCT01856192)
Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10
| Intervention | proportion of participants (Number) |
|---|
| Arm A (R2CHOP) | 0.826 |
| Arm B (RCHOP) | 0.751 |
Proportion of Patients With Complete Response
Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy. (NCT01856192)
Timeframe: Assessed every 3 months for 2 years, every 6 months for year 3, and then annually for years 4-10
| Intervention | proportion of participants (Number) |
|---|
| Arm A (R2CHOP) | 0.73 |
| Arm B (RCHOP) | 0.68 |
Duration of Response (DOR)
"Duration of response was defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause.~Median DOR was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment." (NCT01881789)
Timeframe: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively.
| Intervention | months (Median) |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | NA |
Number of Participants With Dose-Limiting Toxicities (DLTs)
"DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. A DLT is defined as any of the following treatment-related events:~Any ≥ Grade 3 nonhematologic toxicity with the following conditions:~≥ Grade 3 nausea, vomiting, diarrhea, or constipation only if for > 7 days despite optimal supportive care~Asymptomatic Grade 3 hypophosphatemia, Grade 3 hyperglycemia or toxicity solely due to dexamethasone, ≥ Grade 3 rash attributed to lenalidomide, and Grade 3 fatigue for < 14 days were not considered DLTs~Grade 4 neutropenia: absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting ≥ 7 days, despite myeloid growth factor support~Febrile neutropenia~Grade 4 thrombocytopenia for ≥ 7 days or < 7 days with ≥ Grade 2 clinically significant bleeding or < 10,000 platelets requiring platelet transfusion, or Grade ≥ 3 with clinically significant bleeding or requiring platelet transfusion." (NCT01881789)
Timeframe: Cycle 1, 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | 2 |
| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | 2 |
| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | 2 |
| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | 0 |
| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | 1 |
| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | 0 |
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever occurred first. Median PFS was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment. (NCT01881789)
Timeframe: From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively
| Intervention | months (Median) |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | NA |
| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | NA |
Number of Participants With Treatment-emergent Adverse Events (AEs)
"Adverse events (AEs) were graded using NCI-CTCAE (version 4.03) and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE.~A serious AE is an event that met 1 or more of the following criteria:~Death~Life-threatening experience~Required inpatient hospitalization or prolongation of an existing hospitalization~Resulted in persistent or significant disability/incapacity~A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject~Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above.~Treatment-related AEs are those considered related to at least 1 study drug by the investigator." (NCT01881789)
Timeframe: From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Any treatment-emergent adverse event (TEAE) | TEAE ≥ grade 3 | Serious adverse events | TEAEs leading to discontinuation of study drug | Fatal adverse events | Treatment-related adverse events (TRAE) | TRAE ≥ grade 3 | Treatment-related serious adverse events | TRAEs leading to discontinuation of study drug |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | 3 | 3 | 2 | 1 | 0 | 3 | 3 | 2 | 1 |
,| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | 7 | 6 | 4 | 1 | 0 | 7 | 6 | 4 | 1 |
,| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | 3 | 2 | 1 | 0 | 0 | 3 | 2 | 1 | 0 |
,| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | 3 | 3 | 2 | 1 | 0 | 3 | 2 | 1 | 1 |
,| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | 3 | 3 | 3 | 2 | 0 | 3 | 2 | 2 | 2 |
,| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | 2 | 2 | 1 | 1 | 0 | 2 | 2 | 1 | 1 |
Plasma Oprozomib Concentration
"Plasma samples for oprozomib concentration assays were only collected for participants in the 5/14 dosing schedule groups.~Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry." (NCT01881789)
Timeframe: Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI.
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 day 1, 1 - 2.5 hours post EOI | Cycle 1 day 1, 2.75 - 5 hours post EOI | Cycle 3 day 1, predose | Cycle 3 day 1, 1 - 2.5 hours post EOI | Cycle 3 day 1, 2.75 - 5 hours post EOI |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | 497 | 299 | 0.0 | 111 | 2.00 |
,| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | 632 | 15.8 | 142 | 175 | 255 |
,| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | 697 | 78.0 | 0.0 | 178 | 69.1 |
Overall Response Rate (ORR)
"ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.~PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.~VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).~CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.~sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). (NCT01881789)
Timeframe: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively
| Intervention | percentage of participants (Number) |
|---|
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | 66.7 |
| Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | 57.1 |
| Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | 66.7 |
| Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | 100.0 |
| Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | 50.0 |
| Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | 100.0 |
Percent of Bone Marrow-Derived Multiple Myeloma (MM) Cells Expressing Cell Surface CS1 at Time of Progression
"CS1 (CD2 subset-1, also known as CRACC, SLAMF7, CD319) expression levels in multiple myeloma cells were analyzed from bone-marrow aspirates collected at time of progression.~The following conditions were considered to describe multiple myeloma cells expressing CS1 (CS1+/CD38++/CD138+/CD56+/CD19-/CD45DIM)" (NCT01891643)
Timeframe: Time of progression (up to approximately 54 months from pre-treatment screening)
| Intervention | Percent of cells expressing CS1 (Median) |
|---|
| E-Ld Cohort | 46.59 |
| Ld Cohort | 84.62 |
Number of Participants With IgG Response
IgG response defined as having improvement in IgG level by at least 25% at 6 months, compared to baseline. (NCT01924169)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide | 0 |
Number of Participants With Response
Primary endpoint is response rate (RR) measured by the proportion of patients receiving the combination, whose disease stabilizes, or returns to at least its previous response level prior to progression, assessed at 3-months after starting the combination.1.Stringent Complete Remission (sCR): Follows criteria for CR, plus:Normal FLC ratio, Absence of clonal cells in the BM; Complete Remission (CR) All of the following criteria are met:Negative SIFE and UIFE:Disappearance of any soft tissue plasmacytomas:< 5% plasma cells in the BM. 2.Very Good Partial Response (VGPR):One or more of the following must be present:Serum and urine M-protein detectable by immunofixation but not on electrophoresis:≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours.Partial Response (PR) Both of the following must be present:≥ 50% reduction in SPEP:Reduction in 24-hour UPEP by ≥ 90% or to < 200 mg/24 hours.3.Stable Disease (SD)Does not meet the criteria for CR, VGPR, PR, or PD.4.Pr (NCT01927718)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Thalidomide + Lenalidomide | 2 |
Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC
Duration of response (DOR) was defined as the time from initial response (at least PR) until documented progressive disease (PD) or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free. (NCT01938001)
Timeframe: From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
| Intervention | months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | 36.6 |
| Rituximab + Placebo | 21.7 |
Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC
DOCR was defined as the time from initial CR until documented PD or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free. (NCT01938001)
Timeframe: From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
| Intervention | months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | NA |
| Rituximab + Placebo | NA |
Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)
Time to next anti-lymphoma treatment (TTNLT) was defined as the time from date of randomization to date of first documented administration of a new anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy or immunotherapy). The time to the next anti-lymphoma treatment was of special interest to the study. (NCT01938001)
Timeframe: From date of randomization to date of first documented administration of a new anti-lymphoma treatment (Average of 55.71 months and a maximum up to 95.2 months)
| Intervention | Months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | 73.1 |
| Rituximab + Placebo | 31.8 |
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)
Progression-free survival (PFS) was defined as the time from date of randomization into the study to the first observation of documented disease progression or death due to any cause, whichever occurred first. PFS was based on the data from the IRC review using the modified 2007 International Working Group Response Criteria (IWGRC) using FDA censoring rules. (NCT01938001)
Timeframe: From randomization of study drug up to disease progression or death, which occurred first; up to the data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
| Intervention | months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | 39.4 |
| Rituximab + Placebo | 14.1 |
Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC
Event-free survival (EFS) was defined as the time from date of randomization to date of first documented progression, relapse, institution of new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy) or death from any cause. Responding participants and those who were lost to follow up were censored at their last tumor assessment date. (NCT01938001)
Timeframe: From date of randomization to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
| Intervention | months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | 27.6 |
| Rituximab + Placebo | 13.9 |
Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC
DCCR was defined as the percentage of participants with a best response of complete response (CR) that lasted no less than one year (≥ 48 weeks) during the study prior to administration of new anti-lymphoma therapy. A CR is defined as a complete disappearance of any disease-related symptoms and normalization of biochemical abnormalities. (NCT01938001)
Timeframe: From first dose of investigational product (IP) to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomiade arm and 11.04 months in the rituximab/placebo arm
| Intervention | Percentage of Participants (Number) |
|---|
| Rituximab + Lenalidomide (R^2) | 25.3 |
| Rituximab + Placebo | 11.1 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs include AEs that started or worsened between the date of the first dose and 28 days after the date of the last dose. A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death (NCT01938001)
Timeframe: From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any TEAE Related to Lenalidomide/Placebo (LEN/PBO) | Any TEAE Related to Rituximab (RIT) | Any Serious TEAE | Any Serious TEAE Related to LEN/PBO | Any Serious TEAE Related to RIT | Any CTCAE Grade (GR) 3/4 TEAE | Any CTCAE GR 3/4 TEAE Related to LEN/PBO | Any CTCAE GR 3/4 TEAE Related to RIT | Any GR 5 TEAE | Any TEAE Leading to Dose Reduction LEN/PBO | Any TEAE Leading to Dose Interruption LEN/PBO | Any TEAE Leading to Dose Interruption RIT | Any TEAE Leading to Discontinuation of LEN/PBO | Any TEAE Leading to Discontinuation of RIT |
|---|
| Rituximab + Lenalidomide (R^2) | 174 | 159 | 134 | 45 | 23 | 13 | 121 | 101 | 57 | 2 | 46 | 113 | 59 | 15 | 6 |
,| Rituximab + Placebo | 173 | 118 | 105 | 25 | 8 | 4 | 58 | 38 | 20 | 2 | 6 | 47 | 38 | 9 | 2 |
Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC
Percentage of participants with an objective response is defined as having a response of at least a PR during the study without administration of new anti-lymphoma therapy. A complete response = a complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities; a partial response (PR) = 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. (NCT01938001)
Timeframe: From date of first dose to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
| Intervention | Percentage of Participants (Number) |
|---|
| Rituximab + Lenalidomide (R^2) | 77.5 |
| Rituximab + Placebo | 53.3 |
Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC
Percentage of participants with a best response of at CR during the study without administration of new anti-lymphoma therapy. A CR = Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. (NCT01938001)
Timeframe: From date of first dose up to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
| Intervention | Percentage of Participants (Number) |
|---|
| Rituximab + Lenalidomide (R^2) | 33.7 |
| Rituximab + Placebo | 18.3 |
Kaplan-Meier Estimate of Overall Survival (OS)
Overall survival was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented. (NCT01938001)
Timeframe: From date of randomization to death due to any cause (Average of 55.71 months and a maximum up to 95.2 months)
| Intervention | Months (Median) |
|---|
| Rituximab + Lenalidomide (R^2) | NA |
| Rituximab + Placebo | NA |
Objective Response Rate (ORR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. Per protocol, pooled Cohort 5 was not planned to be evaluated statistically compared to a fixed efficacy target. The percentage of participants with CR and PR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 38.9 |
Objective Response Rate (ORR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. The pooled Cohort 4 sub-cohorts were evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 25% using a binomial exact test. The percentage of participants with CR and PR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 22.1 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 72.2 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
ORR was evaluated for each of Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 66.7 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 50.0 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 36.4 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was >50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 33.3 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Indeterminate Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for participants with an indeterminate (missing) PD-L1 status. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 47.4 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of <1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 50.0 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of <1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 75.0 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 0.0 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 7.1 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 0.0 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was >50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of <1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 25.0 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Negative Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 negative (PD-L1 of <1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 11.4 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 54.5 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 27.3 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 100.0 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 0.0 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 6.7 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide): Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and for nodal masses. PR was >50% decrease in the sum of product diameters for ≤6 target dominant masses for lymph nodes, spleen nodules, and liver nodules and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 75.0 |
Objective Response Rate (ORR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
ORR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. Per protocol, Cohorts 4A, 4B, 4C, and 4D were not planned to be compared to an efficacy target. The percentage of participants with CR and PR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 47.6 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 50.0 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 10.0 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 12.2 |
Overall Survival (OS)
OS was defined as the time from first dose of study treatment to death due to any cause. OS was calculated from product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 6.0 |
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 20.2 |
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | NA |
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 37.1 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 23.8 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | NA |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 4.9 |
Overall Survival (OS) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
OS was defined as the time from first dose of study treatment to death due to any cause. OS was calculated from product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 23.0 |
Overall Survival (OS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
OS was defined as the time from first dose of study treatment to death due to any cause. OS was calculated from product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 12.0 |
Progression-free Survival (PFS) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. PD was defined as ≥1 of the following: increase of ≥25% from baseline of serum or urine M-component or >10 mg/dl difference between involved and uninvolved free light chain levels; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; or hypercalcemia. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 2.7 |
Progression-free Survival (PFS) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. PD was the appearance of any new lesion, >50% increase in the sum of product diameters (SPD) of ≥1 lymph node, or a >50% increase in the longest diameter of a previous lymph node, lesions positron emission tomography (PET) positive if 18F-fluorodeoxyglucose (FDG)-avid lymphoma or PET positive prior to therapy for lymph nodes; >50% increase from nadir in the SPD of previous lesions in the liver and spleen; or new or recurrent involvement of the bone marrow. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 8.7 |
Progression-free Survival (PFS) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. PD was the appearance of any new lesion, >50% increase in the sum of product diameters (SPD) of ≥1 lymph node, or a >50% increase in the longest diameter of a previous lymph node, lesions positron emission tomography (PET) positive if 18F-fluorodeoxyglucose (FDG)-avid lymphoma or PET positive prior to therapy for lymph nodes; >50% increase from nadir in the SPD of previous lesions in the liver and spleen; or new or recurrent involvement of the bone marrow. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 1.7 |
Progression-free Survival (PFS) in Participants Pooled From the Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. PD was the appearance of any new lesion, >50% increase in the sum of product diameters (SPD) of ≥1 lymph node, or a >50% increase in the longest diameter of a previous lymph node, lesions positron emission tomography (PET) positive if 18F-fluorodeoxyglucose (FDG)-avid lymphoma or PET positive prior to therapy for lymph nodes; >50% increase from nadir in the SPD of previous lesions in the liver and spleen; or new or recurrent involvement of the bone marrow. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | 5.5 |
Progression-free Survival (PFS) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD was assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. PD was the appearance of any new lesion, >50% increase in the sum of product diameters (SPD) of ≥1 lymph node, or a >50% increase in the longest diameter of a previous lymph node, lesions positron emission tomography (PET) positive if 18F-fluorodeoxyglucose (FDG)-avid lymphoma or PET positive prior to therapy for lymph nodes; >50% increase from nadir in the SPD of previous lesions in the liver and spleen; or new or recurrent involvement of the bone marrow. PFS was calculated from the Kaplan-Meier method for censored data. PFS as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 19.0 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 7.3 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 1.7 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 1.4 |
Stringent Complete Remission (sCR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
sCR was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. sCR was defined as complete response [CR] plus normal serum free light-chain ratio and absence of clonal cells in bone marrow. CR criteria are negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and ≤5% plasma cells in the bone marrow. The percentage of participants with sCR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of partiicpants (Number) |
|---|
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 0.0 |
Time to Progression (TTP) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
TTP was defined as the time from first dose of study treatment to disease progression. Progressive disease was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. PD was defined as ≥1 of the following: increase of ≥25% from baseline of serum or urine M-component or >10 mg/dl difference between involved and uninvolved free light chain levels; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; bone marrow plasma cell percentage absolute % must be ≥10%; or hypercalcemia. The TTP as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 2.7 |
Objective Response Rate (ORR) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. PD-L1 was assessed by immunohistochemistry (IHC). The percentage of participants with CR and PR as assessed by the investigator is presented for PD-L1 positive (PD-L1 of ≥1%) participants. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | 18.8 |
Complete Remission Rate (CRR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
CRR was defined as the percentage of participants with complete remission according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. Complete remission was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. Cohort 3 was evaluated statistically by comparing the complete remission for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. The percentage of participants with complete remission as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 22.6 |
Complete Response (CR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
CR was assessed according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR was defined as negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and <5% plasmacytomas in the bone marrow. The percentage of participants with CR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 0.0 |
Cytogenic Complete Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Cytogenic complete response was evaluated by detection of chromosomal abnormalities by cytogenic techniques and assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Cytogenic complete response was defined as the disappearance of the chromosomal abnormality detected pre-treatment without the appearance of new chromosomal abnormalities. The percentage of participants with cytogenic complete response as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 11.1 |
Cytogenic Partial Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Cytogenic partial response was evaluated by detection of chromosomal abnormalities by cytogenic techniques and assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Cytogenic partial response was defined as ≥50% reduction of the chromosomal abnormality detected pre-treatment. The percentage of participants with cytogenic partial response as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 11.1 |
Duration of Response (DOR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 25.0 |
Duration of Response (DOR) in Participants Pooled From Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)
For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 5 (Pembrolizumab + 20 or 25 mg Doses of Lenalidomide) | NA |
Duration of Response (DOR) in Participants Pooled From the Cohort 4 Non-Hodgkin Lymphoma (NHL) Sub-Cohorts (Cohorts 4A+4B+4C+4D)
For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Pooled Cohort 4 Sub-cohorts (Cohorts 4A+4B+4C+4D) | NA |
Duration of Response (DOR) in the Cohort 4 Non-Hodgkin Lymphoma (NHL) Individual Sub-Cohorts (Cohorts 4A, 4B, 4C, and 4D)
DOR was evaluated for each of the Cohort 4 sub-cohorts: 4A (primary mediastinal B-cell lymphoma), 4B (grey zone, splenic marginal zone, and mantle cell lymphomas), 4C (follicular lymphoma), and 4D (diffuse large B-Cell lymphoma). For participants who demonstrated a confirmed Complete Response (CR) or partial response (PR), DOR was defined as the time from CR or PR to documented disease progression or death. CR and PR were assessed according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. DOR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Months (Median) |
|---|
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | NA |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | NA |
| Cohort 4C: R/R Follicular Lymphoma (FL) | NA |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 13.6 |
Erythroid Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Erythroid response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Erythroid response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criteria for an erythroid response include: hemoglobin (Hgb) increase by ≥1.5 grams/deciliter (g/dl) from pretreatment or reduction of ≥4 transfusions/8 weeks compared with the pre-treatment transfusion number in the previous 8 weeks. Only transfusions given for a Hgb of ≤9.0 g/dl pretreatment counted for response evaluation. The percentage of participants with an erythroid response as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 7.1 |
Marrow Complete Response (mCR) in Cohort 1: Myelodysplastic Syndrome (MDS)
mCR was defined as ≤5% myeloblasts in the bone marrow with a decrease in myeloblasts ≥50% over pretreatment according to the modified International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. The percentage of participants with mCR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 18.5 |
Neutrophil Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Neutrophil response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Neutrophil response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criterion for a neutrophil response was a ≥100% increase in neutrophil count from pre-treatment and an absolute increase of >0.5 x 10^9/Liter. The percentage of participants with a neutrophil response as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 3.6 |
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 6 |
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 2 |
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 3 |
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 1 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 1 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 3 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 2 |
| Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 20 mg (RP2D) | 0 |
| Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 25 mg | 1 |
Number of Participants Who Experienced One or More Adverse Events (AEs):
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 27 |
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 28 |
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 31 |
| Cohort 4A: R/R Primary Mediastinal B-cell Lymphoma (PMBCL) | 21 |
| Cohort 4B: Other Non-Hodgkin Lymphoma: Grey Zone, Splenic Marginal Zone, and Mantle Cell Lymphomas | 4 |
| Cohort 4C: R/R Follicular Lymphoma (FL) | 21 |
| Cohort 4D: R/R Diffuse Large B-Cell Lymphoma (DLBCL) | 38 |
| Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 20 mg (RP2D) | 13 |
| Cohort 5: R/R DLBCL Pembrolizumab+Lenalidomide 25 mg | 5 |
Objective Response Rate (ORR) in Cohort 1: Myelodysplastic Syndrome (MDS)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. CR was demonstrated by ≤5% myeloblasts with normal maturation of all cell lines in the bone marrow (persistent dysplasia will be noted) and normal findings for hemoglobin, platelet count, neutrophil count, and absence of blasts in the blood. PR was all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pre-treatment but still >5%. Cellularity and morphology are not relevant. Cohort 1 was evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 10% using a binomial exact test. The percentage of participants with CR and PR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 0.0 |
Objective Response Rate (ORR) in Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM)
ORR was defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) 2006 response criteria. CR=negative immunofixation of serum and urine+disappearance of soft tissue plasmacytomas+≤5% plasma cells in the bone marrow (BM); sCR=stringent complete response, CR as above+normal serum free light-chain ratio and absence of clonal cells in BM; VGPR=serum+urine M-protein (M-p) by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-p+urine M-p <100 mg/24 hr; PR=≥50% reduction of serum M-p+reduction in 24-hour urine M-p by ≥90% or to <200 mg/24 hours. Cohort 2 was evaluated statistically by comparing the ORR for pembrolizumab to a fixed efficacy target of 25% using a binomial exact test. The percentage of participants with CR, sCR, PR, VGPR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 2: Relapsed Refractory/Refractory (rR/R) Multiple Myeloma (MM) | 0.0 |
Objective Response Rate (ORR) in Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL)
ORR was defined as the percentage of participants with response (complete response [CR] or partial response [PR]) according to the revised response criteria for malignant lymphoma per Cheson et al. 2007. CR was demonstrated by disappearance of all evidence of disease in the bone marrow, spleen, liver, and lymph nodes. PR was >50% decrease in the sum of product diameters (SPD) for ≤6 target masses for lymph nodes and >50% decrease in SPD for a single nodule in greatest transverse diameter for spleen and liver, and no size increase in the lymph nodes, spleen, or liver. The percentage of participants who experience ORR as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 3: Relapsed/Refractory (R/R) Hodgkin Lymphoma (HL) | 64.5 |
Platelet Response in Cohort 1: Myelodysplastic Syndrome (MDS)
Platelet response was measured as an evaluation of hematologic improvement and was assessed according to the International Working Group (IWG) response criteria in myelodysplasia per Cheson et al. 2006. Platelet response baseline was based on an average of at least 2 pre-treatment measurements taken ≥1 week apart and not influenced by transfusions. Responses were considered significant if they lasted for ≥8 weeks. Criterion for a platelet response was an absolute increase of ≥30 x 10^9/Liter platelet count for participants with a pre-treatment count of ≥20 x 10^9/Liter and for participants with a pre-treatment count of <20 x 10^9/Liter there must have been an absolute increase to ≥20 x 10^9/Liter and a ≥100% increase in pre-treatment level. The percentage of participants with a platelet response as assessed by the investigator is presented. (NCT01953692)
Timeframe: Up to approximately 78.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: Myelodysplastic Syndrome (MDS) | 7.1 |
Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause. PD= ≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. The median PFS was calculated from the Kaplan-Meier method for censored data. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Months (Median) |
|---|
| Pooled rrMM Cohort | 5.6 |
| Pooled rMM Cohort | 14.3 |
Duration of Response (DOR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
DOR was the time from first evidence of response (stringent complete response [sCR]+complete response [CR], very good partial response [VGPR], partial response [PR]) until disease progression (PD) or death. CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs. PD=≥1 of the following: ≥25% increase from baseline serum/urine M-protein; hypercalcemia; increase between involved/uninvolved FLC levels; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. DOR was calculated using the Kaplan-Meier method for censored data. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Months (Median) |
|---|
| Pooled rrMM Cohort | 16.4 |
| Pooled rMM Cohort | 14.1 |
Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
DCR was the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) ≥12 weeks prior to evidence of disease progression (PD). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+ ≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not on electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR=≥50% reduction of serum M-protein+reduction in 24 hr urinary M-protein by ≥90% or to <200 mg/24 hrs; SD=not meeting the criteria for CR, VGPR, PR, or PD. PD=≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled rrMM Cohort | 84.1 |
| Pooled rMM Cohort | 100.0 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. OS was calculated from product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Months (Median) |
|---|
| Pooled rrMM Cohort | 29.0 |
| Pooled rMM Cohort | 22.5 |
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
DLTs were assessed during Cycle 1 (28 days) and were defined as the occurrence of any of the following judged by the investigator to be possibly, probably or definitely related to study drug: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 3 non-hematologic toxicity lasting >3 days; Gr 3 non-hematologic laboratory value if: medical intervention was required, abnormality led to hospitalization, was renal or liver function related, or persisted for >1 week; Gr 3/4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (associated with bleeding requiring platelet transfusion or life-threatening bleeding); Gr 5 toxicity; or delay of >1 week in initiating Cycle 2 or unable to complete 80% of treatment during the first course of therapy due to drug-related toxicity. DLTs for the rMM cohort were any drug-related adverse events that cannot be managed by dose modification. DLTs are reported for the maximum tolerated dose. (NCT02036502)
Timeframe: Up to 28 days in Cycle 1
| Intervention | Participants (Count of Participants) |
|---|
| Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg | 3 |
| Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg | 0 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg | 0 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg | 0 |
| Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg | 0 |
Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
ORR was the percentage of the participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Percentage of participants (Number) |
|---|
| Pooled rrMM Cohort | 30.2 |
| Pooled rMM Cohort | 70.0 |
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Participants (Count of Participants) |
|---|
| Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg | 0 |
| Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg | 1 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg | 0 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg | 0 |
| Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg | 0 |
| Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg | 4 |
| Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg | 0 |
| Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg | 6 |
Number of Participants Who Experienced One or More Adverse Events (AEs)
An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event. (NCT02036502)
Timeframe: Up to approximately 72.7 months
| Intervention | Participants (Count of Participants) |
|---|
| Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg | 6 |
| Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg | 3 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg | 6 |
| Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg | 1 |
| Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg | 1 |
| Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg | 45 |
| Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg | 1 |
| Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg | 10 |
Phenotypic Changes
Phenotypic changes in peripheral blood cells following CC-5013 (lenalidomide) administration especially in regards to CD3, CD4, CD8 T cells, and NK and NKT cells. (NCT02041325)
Timeframe: 6 weeks
| Intervention | cells/cmm (Median) |
|---|
| Total T cells CD3+ | Helper T cells CD3+/CD4+ | Cytotoxic T cells CD3+/CD8+ | Natural Killer cells CD56+/CD16+ |
|---|
| Lenalidomide | 851.5 | 591 | 296 | 249.5 |
,| Placebo | 715 | 525 | 183 | 228 |
Safety
Number of participants with adverse events as a measure of safety and tolerability (NCT02041325)
Timeframe: 6 weeks
| Intervention | participants (Number) |
|---|
| Lenalidomide | 2 |
| Placebo | 2 |
Quantity of Subjects With a T-cell Response
Participants who displayed a T cell responses against HbSAg following vaccination (NCT02041325)
Timeframe: 6 weeks
| Intervention | participants (Number) |
|---|
| Lenalidomide | 0 |
| Placebo | 0 |
Positive for Hepatitis B Surface Antigen
The number of participants who test positive for the antibody titer against hepatitis B surface antigen (HbSAg). (NCT02041325)
Timeframe: 6 weeks
| Intervention | participants (Number) |
|---|
| Lenalidomide | 4 |
| Placebo | 3 |
Time to Disease Progression (TTP)
TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be >10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to plasma cell (PC) proliferative disorder. (NCT02076009)
Timeframe: From randomization to disease progression (up to 21 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 18.43 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | NA |
Time to Response
Time to response was defined as the time between the date of randomization and the first efficacy evaluation that the participant met all criteria for partial response (PR) or better. (NCT02076009)
Timeframe: From randomization up to first documented CR or PR (up to 21 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 1.3 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 1.0 |
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Minimal residual disease was assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR). CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4 color flow cytometry. The MRD negativity rate was defined as the percentage of participants who had negative MRD assessment at any time point after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^ minus (-) 4, 10^-5, 10^-6 threshold. (NCT02076009)
Timeframe: From randomization to the date of first documented evidence of PD (up to 87.5 months)
| Intervention | percentage of participants (Number) |
|---|
| MRD negative rate (10^-4) | MRD negative rate (10^-5) | MRD negative rate (10^-6) |
|---|
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 40.6 | 33.2 | 13.3 |
,| Lenalidomide, Low-dose Dexamethasone (Rd) | 10.2 | 6.7 | 1.8 |
Time to Subsequent Anticancer Treatment
Time to subsequent anticancer treatment was defined as the time from randomization to the start of subsequent anticancer treatment or death due to progressive disease (PD), whichever occurs first. (NCT02076009)
Timeframe: From randomization to date of start of subsequent anticancer treatment or death due to PD, whichever occured first (up to 87.5 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 23.1 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 69.3 |
Duration of Response (DOR)
DOR was defined for participants with confirmed response (PR or better) as time between first documentation of response and disease progression/death due to PD, whichever occurs first. PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be >10mg/dL; Definite increase in size of existing bone lesions/soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5mg/dL) that can be attributed solely to PC proliferative disorder. (NCT02076009)
Timeframe: From randomization to the date of first documented evidence of PD (up to 21 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 17.4 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | NA |
Overall Response Rate
Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required. (NCT02076009)
Timeframe: From randomization to disease progression (up to 21 months)
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 76.4 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 92.9 |
Overall Survival (OS)
Overall survival was measured from the date of randomization to the date of the participant's death. (NCT02076009)
Timeframe: From randomization to date of death due to any cause (up to 87.5 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 51.84 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 67.58 |
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
VGPR or better is defined as the percentage of participants who achieved VGPR, complete response (CR) and stringent complete response (sCR) according to the International Myeloma Working Group criteria (IMWG). IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4 color flow cytometry. (NCT02076009)
Timeframe: From randomization to disease progression (up to 21 months)
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 44.2 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | 75.8 |
Progression-free Survival (PFS)
PFS: duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD: defined as meeting any 1 of following criteria: Increase of greater than equal to (>=)25 percent(%) in level of serum M-protein from lowest response value and absolute increase must be >=0.5 gram per deciliter (g/dL); Increase of >=25% in 24-hours(h) urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24h; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be >10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to plasma cell (PC) proliferative disorder. (NCT02076009)
Timeframe: From randomization to either disease progression or death whichever occurs first (up to 21 months)
| Intervention | months (Median) |
|---|
| Lenalidomide, Low-dose Dexamethasone (Rd) | 18.43 |
| Daratumumab, Lenalidomide, Low-dose Dexamethasone (DRd) | NA |
Phase 2: Overall Survival (OS)
OS is defined as the time from the date of the first dose of study drug to the date of death due to any cause. For participants not known to have died at or prior to the database lock date, OS data was censored at the date last known alive. Participants who withdrew consent prior to study closure were censored on the date of the consent withdrawal. 2-sided 95% CI was estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.
| Intervention | months (Median) |
|---|
| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 14.7 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 11.6 |
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 14.2 |
Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization > 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. (NCT02077166)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any Grade >=3 TEAE | Any Study Drug-Related TEAE | Any Grade >=3 Study Drug-Related TEAE | Any Ibrutinib-Related TEAE | Any Grade >=3 Ibrutinib-Related TEAE | Any Lenalidomide-Related TEAE | Any Grade >=3 Lenalidomide-Related TEAE | Any Rituximab-Related TEAE | Any Grade >= 3 Rituximab-Related TEAE | Any TEAE Leading to Dose Reduction of Any Study Drug | Any TEAE Leading to Dose Reduction of Ibrutinib | Any TEAE Leading to Dose Reduction of Lenalidomide | Any TEAE Leading to Dose Delay of Any Study Drug | Any TEAE Leading to Dose Delay of Ibrutinib | Any TEAE Leading to Dose Delay of Lenalidomide | Any TEAE Leading to Dose Delay of Rituximab | Any TEAE Leading to Discontinuation of Any Study Drug | Any TEAE Leading to Discontinuation of Ibrutinib Dose | Any TEAE Leading to Discontinuation of Lenalidomide Dose | Any TEAE Leading to Discontinuation of Rituximab Dose | Any Serious TEAE | Any Grade >=3 Serious TEAE | Any Treatment-Related Serious TEAE | Any Ibrutinib-Related Serious TEAE | Any Lenalidomide-Related Serious TEAE | Any Rituximab-Related Serious TEAE | Any Fatal TEAE |
|---|
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | 7 | 6 | 5 | 3 | 5 | 3 | 5 | 3 | 4 | 2 | 0 | 0 | 0 | 4 | 4 | 3 | 1 | 2 | 2 | 2 | 2 | 6 | 6 | 2 | 2 | 2 | 2 | 2 |
,| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1) | 12 | 11 | 12 | 10 | 12 | 10 | 12 | 9 | 6 | 1 | 4 | 3 | 2 | 6 | 6 | 6 | 4 | 4 | 4 | 4 | 3 | 4 | 4 | 0 | 0 | 0 | 0 | 0 |
,| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | 9 | 9 | 9 | 8 | 9 | 7 | 9 | 8 | 7 | 7 | 4 | 4 | 3 | 7 | 7 | 7 | 6 | 3 | 3 | 3 | 3 | 7 | 6 | 4 | 4 | 4 | 2 | 2 |
,| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | 9 | 9 | 8 | 7 | 8 | 7 | 8 | 7 | 6 | 5 | 4 | 3 | 4 | 8 | 8 | 7 | 4 | 2 | 2 | 2 | 2 | 5 | 4 | 2 | 2 | 2 | 1 | 1 |
,| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | 8 | 7 | 8 | 7 | 8 | 6 | 8 | 6 | 7 | 3 | 5 | 3 | 4 | 8 | 8 | 8 | 4 | 1 | 1 | 1 | 1 | 6 | 6 | 3 | 3 | 3 | 0 | 1 |
Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization > 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death. (NCT02077166)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug. Phase 2 median duration of ibrutinib exposure was 4.9 months; median duration of lenalidomide exposure was 4.7 months; median total number of doses of rituximab received was 5.0.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any Grade >=3 TEAE | Any Study Drug-Related TEAE | Any Grade >=3 Study Drug-Related TEAE | Any Ibrutinib-Related TEAE | Any Grade >=3 Ibrutinib-Related TEAE | Any Lenalidomide-Related TEAE | Any Grade >=3 Lenalidomide-Related TEAE | Any Rituximab-Related TEAE | Any Grade >= 3 Rituximab-Related TEAE | Any TEAE Leading to Dose Reduction of Any Study Drug | Any TEAE Leading to Dose Reduction of Ibrutinib | Any TEAE Leading to Dose Reduction of Lenalidomide | Any TEAE Leading to Dose Delay of Any Study Drug | Any TEAE Leading to Dose Delay of Ibrutinib | Any TEAE Leading to Dose Delay of Lenalidomide | Any TEAE Leading to Dose Delay of Rituximab | Any TEAE Leading to Discontinuation of Any Study Drug | Any TEAE Leading to Discontinuation of Ibrutinib Dose | Any TEAE Leading to Discontinuation of Lenalidomide Dose | Any TEAE Leading to Discontinuation of Rituximab Dose | Any Serious TEAE | Any Grade >=3 Serious TEAE | Any Treatment-Related Serious TEAE | Any Ibrutinib-Related Serious TEAE | Any Lenalidomide-Related Serious TEAE | Any Rituximab-Related Serious TEAE | Any Fatal TEAE |
|---|
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 89 | 81 | 85 | 66 | 82 | 60 | 83 | 65 | 62 | 31 | 37 | 21 | 35 | 69 | 66 | 63 | 16 | 18 | 16 | 18 | 10 | 57 | 50 | 28 | 26 | 26 | 9 | 12 |
,| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 55 | 51 | 52 | 41 | 50 | 36 | 51 | 40 | 37 | 18 | 23 | 12 | 21 | 40 | 38 | 37 | 10 | 11 | 11 | 11 | 6 | 32 | 29 | 16 | 14 | 16 | 4 | 8 |
,| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 34 | 30 | 33 | 25 | 32 | 24 | 32 | 25 | 25 | 13 | 14 | 9 | 14 | 29 | 28 | 26 | 6 | 7 | 5 | 7 | 4 | 25 | 21 | 12 | 12 | 10 | 5 | 4 |
Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
The dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A Dose Level Review Committee evaluated safety data following completion of each dose observation period of the Phase 1b portion. (NCT02077166)
Timeframe: Estimated median time on study in Phase 1b was 59.6 months.
| Intervention | mg (Number) |
|---|
| All Phase 1b Participants | 20 |
Phase 2: CR Rate
The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (see Cheson, 2014 for detailed criteria) in response-evaluable population, as assessed by the Investigator. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 32.1 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 21.9 |
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 28.2 |
Phase 2: Duration of Response (DOR)
DOR is defined as the time from the date of the first documented response (CR or PR) to the first documented evidence of disease progression (PD) according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause. For participants who had achieved an overall response but did not die or progress at the time of analysis, DOR was censored on the date of the last adequate post-baseline disease assessment, or on the date of the first occurrence of response (CR or PR) if there was no disease assessment afterwards. 2-sided 95% CI is estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.
| Intervention | months (Median) |
|---|
| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 38.3 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 28.6 |
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 38.3 |
Phase 2: Overall Response Rate (ORR)
The ORR was defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014), as assessed by the investigator in response-evaluable population. The 95% confidence interval (CI) was calculated using the exact method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 52.8 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 43.8 |
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 49.4 |
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from the date of the first dose of study drug to confirmed PD according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014) or death from any cause, whichever occurred first. For participants without disease progression or death, PFS data was censored at the date of the last tumor assessment. 2 sided 95% CI is estimated by Kaplan-Meier method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 2 was 35.0 months.
| Intervention | months (Median) |
|---|
| Phase 2: Enrolled at Lenalidomide Dose 20 mg | 5.4 |
| Phase 2: Enrolled at Lenalidomide Dose 25 mg | 4.7 |
| Phase 2 Total: Enrolled at Lenalidomide Dose 20 or 25 mg | 5.4 |
Phase 1b: Complete Response (CR) Rate
The CR rate was defined as the percentage of participants who achieve a CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease, as assessed by the Investigator. (NCT02077166)
Timeframe: Estimated median time on Phase 1b study was 59.6 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1) | 33.3 |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | 0 |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | 42.9 |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | 11.1 |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | 50.0 |
| Phase 1b Total: Enrolled at Lenalidomide Dose 10 to 25 mg (All Dose Levels) | 27.5 |
Phase 1b: ORR
The ORR was defined as the percentage of participants who achieve either a PR or CR, according to the Revised International Working Group Response Criteria for Malignant Lymphoma (Cheson 2007), as assessed by the Investigator in response-evaluable population, where CR=disappearance of all evidence of disease and PR=regression of measurable disease and no new sites. The 95% CI was calculated using the exact method. (NCT02077166)
Timeframe: Estimated median time on study in Phase 1b was 59.6 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1) | 44.4 |
| Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1) | 0 |
| Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+) | 71.4 |
| Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2) | 22.2 |
| Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3) | 75.0 |
| Phase 1b Total: Enrolled at Lenalidomide Dose 10 to 25 mg (All Dose Levels) | 42.5 |
Overall Survival
Overall Survival (OS) is defined as the time from Stem Cell Transplant (SCT) to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT02086552)
Timeframe: Time from SCT to death due to any cause, assessed up to 3 years
| Intervention | years (Median) |
|---|
| Treatment (Sonidegib, Lenalidomide) | NA |
Progression-free Survival
The progression-free survival time is defined as the time from SCT to progression or death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. Here, we are reporting the proportion of patients that have not had a PFS event two years after SCT. (NCT02086552)
Timeframe: Time from SCT to progression or death due to any cause, assessed at 2 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Sonidegib, Lenalidomide) | 0.76 |
Progression-free Survival (1 Year Survival Rate)
The progression-free survival time is defined as the time from SCT to progression or death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. Here, we are reporting the proportion of patients that have not had a PFS event one year after SCT. (NCT02086552)
Timeframe: Time from SCT to progression or death due to any cause, assessed at 1 year
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Sonidegib, Lenalidomide) | 0.88 |
Complete Response (CR) Duration
Complete Response is defined as disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count >/= 1.0 x 10^9/L and platelet count>/= 100 x 10^9, and bone marrow differential showing NCT02126553)
Timeframe: Up to 7 years
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide) | NA |
Event-free Survival (EFS)
Time from date of treatment start until the date of first objective documentation of disease-relapse, death or discontinuation due to adverse events. (NCT02126553)
Timeframe: Up to 7 Years
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide) | 12 |
Overall Survival (OS)
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. (NCT02126553)
Timeframe: Up to 7 Years
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide) | NA |
Relapse-free Survival (RFS)
Time from date of treatment start until the date of first objective documentation of disease-relapse. (NCT02126553)
Timeframe: Up to 7 Years
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide) | 21.5 |
The Remission Rate for Participants With High-risk Myeloma
Toward improving the clinical outcomes of research subjects with high-risk MM (HR-MM) in the context of the immediately preceding TT5 trial 2008-02 and TT3 trials 2003-33 and 2006-66, TT5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission (AS-CR-2) by reducing host-imposed toxicity and thus facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib (CFZ). This will result in avoiding MM re-growth that, we postulate, ensued in TT3 during recovery phases from severe de-conditioning. Furthermore, we speculate that the incidence of positive minimal residual disease (MRD) will be reduced with the addition of one cycle of consolidation therapy. (NCT02128230)
Timeframe: from baseline to either death or study completion for each subject (up to approximately 48 months)
| Intervention | Participants (Number) |
|---|
| Total Therapy 5B | 0 |
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy-ORR
Part 2 - Overall Response rate will be defined as the proportion of subjects who achieve either a Complete Response or a Partial Response according to the international Working Group Response Criteria for NHL as assessed by investigator. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose
| Intervention | Participants (Count of Participants) |
|---|
| All Subjects Treated at RP2D | 16 |
| ABC Subjects Treated at RP2D | 9 |
Number of Participants With Complete Responses (CR) and Partial Responses (PR) as a Measure of Efficacy
Part-1: Overall Response rate (ORR) will defined as the proportion of subjects who achieve either a CR or a PR according to the international Working Group Response Criteria for NHL as assessed by investigator. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Dose Level 1 | 1 |
| Part 1: Dose Level 2 | 2 |
| Part 1: Dose Level 3 | 0 |
| Part 1: Dose Level 4 | 3 |
| Part 1: All Treated | 6 |
Progression Free Survival (PFS) and Overall Survival (OS) as a Measure of Efficacy
Part 2: PFS will be measured as time from first study drug administration to disease progression or death from any cause. OS will be measured from the time of first study drug administration until the date of death using Kaplan-Meier methodology. (NCT02142049)
Timeframe: From initial dose date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose, up to 36 months at the most.
| Intervention | Months (Median) |
|---|
| Progression Free Survival (PFS) | Overall Survival (OS) |
|---|
| ABC Subjects Treated at RP2D | 4.86 | 15.84 |
,| All Subjects Treated at RP2D | 4.86 | 15.84 |
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Part 2: The frequency (number and percentage) of treatment-emergent adverse events will be reported. (NCT02142049)
Timeframe: 1 year after last subjects received the first dose
| Intervention | Participants (Count of Participants) |
|---|
| All Subjects Treated at RP2D | 26 |
| ABC Subjects Treated at RP2D | 14 |
Number of Participants With Dose-Limiting Toxicities as a Measure of Safety and Tolerability
Part-1: To determine the maximum tolerated dose (MTD) of the combination of ibrutinib and lenalidomide with dose adjusted EPOCH-R (NCT02142049)
Timeframe: 1 year after last subjects received the first dose
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Dose Level 1 | 0 |
| Part 1: Dose Level 2 | 0 |
| Part 1: Dose Level 3 | 0 |
| Part 1: Dose Level 4 | 1 |
| Part 1: All Treated | 1 |
Duration of Response (DOR)
Part 2: DOR will be measured from the time by which the measurement criteria are met for CR or PR until the first date by which recurrent or progressive disease is objectively documented. (NCT02142049)
Timeframe: From initial response date until the date of first documented progression or death from any cause, whichever came first, assessed up to approximately 1 year after the last subject received the first dose.
| Intervention | Months (Median) |
|---|
| All Subjects Treated at RP2D Who Achieved Overall Response | 3.94 |
| ABC Subjects Treated at RP2D Who Achieved Overall Response | 4.09 |
Number of Participants With Any Grade and Grade 3 or Grade 4 (G3/4) Infusion Reactions Over the Entire Study Period
An infusion reaction in this study is defined as any relevant sign or symptom occurring during or after elotuzumab infusion and considered by the investigator as an infusion reaction. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Potentially Life-threatening or disabling, Gr 5=Death. (NCT02159365)
Timeframe: Date of first dose up to 60 days post last dose (approximately 4 years)
| Intervention | Participants (Count of Participants) |
|---|
| # of participants with any grade infusion reaction | # of participants with G3/4 infusion reaction |
|---|
| E-Ld | 3 | 1 |
Number of Participants With Grade 3 or Grade 4 (G3/4) Infusion Reactions by the End of Treatment Cycle 2
Infusion reaction was defined as any relevant sign or symptom occurring during or after elotuzumab infusion and considered by the investigator as an infusion reaction. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Potentially Life-threatening or disabling, Gr 5=Death. (NCT02159365)
Timeframe: From Day 1 to End of cycle 2 treatment (approximately 56 days)
| Intervention | Participants (Number) |
|---|
| E-Ld | 0 |
Number of Participants With a Response
"Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes < 4000/ul, normocellular, <30% lymphocytes, no B-lymphoid nodules, Platelets > 100,000/ul, hemoglobin >11.0 g/dl and Neutrophils >1500/ul.~PR is >/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count > 100,000/ul, Hemoglobin > 11 g/dl and Neutrophils >1500/ul or increase >/= 50% of all over base." (NCT02225275)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Lenalidomide, Obinutuzumab) | 5 |
Time to Next Treatment
The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy. (NCT02225275)
Timeframe: Up to 5 years, 2 months
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide, Obinutuzumab) | 26.9 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. (NCT02225275)
Timeframe: Up to 5 years, 2 months
| Intervention | Months (Median) |
|---|
| Treatment (Lenalidomide, Obinutuzumab) | NA |
Primary: Progression-free Survival (PFS)
PFS is defined as time from date of randomization to either progressive disease (PD) or death, whichever occurs first based on computerized algorithm as per International Myeloma Working Group (IMWG) criteria. PD is defined as an increase of 25 percent (%) from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligram [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be greater than [>]10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to Plasma cell (PC) proliferative disorder. (NCT02252172)
Timeframe: From randomization to disease progression, death, subsequent anti-myeloma therapy, withdrawal of consent to study participation or clinical cut-off (CCO) whichever occurs first (up to 3.5 years)
| Intervention | Months (Median) |
|---|
| Lenalidomide + Dexamethasone (Rd) | 31.87 |
| Daratumumab + Lenalidomide + Dexamethasone (DRd) | NA |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 Global Health Status Score to Day 1 of Cycle 3, 6, 9 and 12
"EORTC QLQ-C30 is 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from 1-not at all to 4-very much to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms." (NCT02252172)
Timeframe: Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)
| Intervention | Score on scale (Least Squares Mean) |
|---|
| Global health status score: Cycle 3 Day 1 | Global health status score: Cycle 6 Day 1 | Global health status score: Cycle 9 Day 1 | Global health status score: Cycle 12 Day 1 |
|---|
| Daratumumab + Lenalidomide + Dexamethasone (DRd) | 4.5 | 6.4 | 8.2 | 8.4 |
,| Lenalidomide + Dexamethasone (Rd) | 1.5 | 5.6 | 7 | 5.4 |
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score to Day 1 of Cycle 3, 6, 9 and 12
EQ-5D-5L is standardized, participant-reported questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L VAS. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5-dimension scores were combined and converted into single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of individual (but allows for values less than 0 by United kingdom [UK] scoring algorithm). (NCT02252172)
Timeframe: Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)
| Intervention | Score on scale (Least Squares Mean) |
|---|
| Change at Cycle 3 Day 1 | Change at Cycle 6 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 12 Day 1 |
|---|
| Daratumumab + Lenalidomide + Dexamethasone (DRd) | 0.107 | 0.136 | 0.124 | 0.141 |
,| Lenalidomide + Dexamethasone (Rd) | 0.08 | 0.116 | 0.124 | 0.113 |
Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) to Day 1 of Cycle 3, 6, 9 and 12
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. (NCT02252172)
Timeframe: Baseline and Day 1 of Cycle 3, 6, 9 and 12 (each Cycle of 28 days)
| Intervention | Score on scale (Least Squares Mean) |
|---|
| Change at Cycle 3 Day 1 | Change at Cycle 6 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 12 Day 1 |
|---|
| Daratumumab + Lenalidomide + Dexamethasone (DRd) | 4.9 | 8 | 10.2 | 10.1 |
,| Lenalidomide + Dexamethasone (Rd) | 2.5 | 5.7 | 7.7 | 4.9 |
Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms
(NCT02253316)
Timeframe: Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Maintenance Arm 1: Ixazomib | 5 |
| Maintenance Arm 2: Lenalidomide | 11 |
Number of Participants With Improvement in Minimal Residual Disease (MRD)
For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | 19 |
MRD-negative Rate After ASCT
For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing (NCT02253316)
Timeframe: Prior to beginning consolidation treatment (Day -28 to Day 0)
| Intervention | Participants (Count of Participants) |
|---|
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | 51 |
Compare Response Rate Between the Two Maintenance Arms
"Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).~sCR requires all of the following:~CR as defined below~Normal free light chain ratio (0.26-1.65)~Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence~CR requires all of the following:~Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine~If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)~<5% plasma cells in the bone marrow~Disappearance of soft tissue plasmacytoma" (NCT02253316)
Timeframe: Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Maintenance Arm 1: Ixazomib | 50 |
| Maintenance Arm 2: Lenalidomide | 80 |
Toxicity of IRD Consolidation
For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | 7 |
Response Rate of IRD Consolidation
For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. (NCT02253316)
Timeframe: After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Consolidation: Ixazomib, Lenalidomide, & Dexamethasone | 49 |
Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug. (NCT02265510)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE | SAE |
|---|
| Phase 1a TGA - INCB052793 100 mg | 6 | 2 |
,| Phase 1a TGA - INCB052793 15 mg | 3 | 0 |
,| Phase 1a TGA - INCB052793 25 mg | 3 | 1 |
,| Phase 1a TGA - INCB052793 35 mg | 6 | 0 |
,| Phase 1a TGA - INCB052793 50 mg | 4 | 2 |
,| Phase 1a TGA - INCB052793 75 mg | 3 | 3 |
,| Phase 1a TGB - INCB052793 25 mg | 3 | 1 |
,| Phase 1a TGB - INCB052793 35 mg | 4 | 2 |
,| Phase 1a TGB - INCB052793 50 mg | 4 | 2 |
,| Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg | 7 | 5 |
,| Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2 | 5 | 4 |
,| Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 16 | 14 |
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg. (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | nM (Mean) |
|---|
| Phase 1a TGA - INCB052793 15 mg | 522 |
| Phase 1a TGA - INCB052793 25 mg | 1110 |
| Phase 1a TGA - INCB052793 35 mg | 1120 |
| Phase 1a TGA - INCB052793 50 mg | 2050 |
| Phase 1a TGA - INCB052793 75 mg | 1840 |
| Phase 1a TGA - INCB052793 100 mg | 2890 |
| Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg | 928 |
| Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2 | 1270 |
| Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 1480 |
| Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 1610 |
Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment
Response rate is defined as the percentage of participants who achieved best overall response (BOR) as determined by IWG response criteria of investigator's assessment. A participant was considered an objective responder based on the following- Solid tumors: participant had a best overall response (BOR) of CR or PR, Lymphoma: participant had a BOR of complete radiologic response/complete metabolic response or partial remission/partial metabolic response, AML: participant had a BOR of CR, CRi, morphological leukemia-free state (MLFS), or PR, MDS: participant had a BOR of CR, PR, or marrow CR, MDS/myeloproliferative neoplasm (MPN): participant had a BOR of CR, PR, or marrow response, MM: participant had a BOR of stringent CR, CR, very good PR, PR, or MR. Subjects are combined by tumor type for this analysis. (NCT02265510)
Timeframe: Baseline through end of study (Up to approximately 4.5 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1a TGA - INCB052793 in Solid Tumors | 0 |
| Phase 1a TGB - INCB052793 in Lymphoma | 0 |
| Phase 1a TGB - INCB052793 in MDS/MPN | 1 |
| Phase 1a TGB - INCB052793 in MM | 0 |
| Phase 1b Cohort B - INCB052793 + Dexamethasone in MM | 2 |
| Phase 1b Cohort F-INCB052793 +Azacytidine in AML | 4 |
| Phase 1b Cohort F-INCB052793 +Azacytidine in MDS | 3 |
| Phase 1b Cohort F-INCB052793 +Azacytidine in MDS/MPN | 2 |
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg. (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | nM*hr (Mean) |
|---|
| Phase 1a TGA - INCB052793 15 mg | 4750 |
| Phase 1a TGA - INCB052793 25 mg | 9170 |
| Phase 1a TGA - INCB052793 35 mg | 8430 |
| Phase 1a TGA - INCB052793 50 mg | 14700 |
| Phase 1a TGA - INCB052793 75 mg | 18300 |
| Phase 1a TGA - INCB052793 100 mg | 27800 |
| Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg | 6390 |
| Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2 | 9580 |
| Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 10200 |
| Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 9380 |
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | nM*hr (Mean) |
|---|
| Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2 | 9870 |
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib
Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | nM (Mean) |
|---|
| Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2 | 1310 |
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Tmax is the time to maximum (peak) observed plasma drug concentration. Summary of Steady-State, Day 15, was evaluated by dosing regimen. For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg. (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | hours (hr) (Median) |
|---|
| Phase 1a TGA - INCB052793 15 mg | 1.1 |
| Phase 1a TGA - INCB052793 25 mg | 0.76 |
| Phase 1a TGA - INCB052793 35 mg | 2.0 |
| Phase 1a TGA - INCB052793 50 mg | 1.1 |
| Phase 1a TGA - INCB052793 75 mg | 2.2 |
| Phase 1a TGA - INCB052793 100 mg | 2.0 |
| Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg | 1.0 |
| Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2 | 1.1 |
| Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 1.1 |
| Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 0.51 |
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib
Tmax is the time to maximum (peak) observed plasma drug concentration. (NCT02265510)
Timeframe: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
| Intervention | hr (Median) |
|---|
| Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2 | 3.5 |
Phase 2: Objective Response Rate (ORR) in Hematological Malignancies
ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria. (NCT02265510)
Timeframe: Baseline through end of study (Up to approximately 4.5 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2 Cohort I-INCB052793 +Azacytidine (AML) | 0 |
| Phase 2 Cohort I-INCB052793 +Azacytidine (MDS) | 1 |
| Phase 2 Cohort J-Itacitinib +Azacitidine (AML) | 1 |
| Phase 2 Cohort J-Itacitinib +Azacitidine (MDS) | 0 |
Phase 2: Number of Participants With at Least One TEAE and SAE
An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug. (NCT02265510)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE | SAE |
|---|
| Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2 | 9 | 7 |
,| Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2 | 10 | 8 |
Objective Response Rate (ORR)
"ORR is the percentage of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) as determined by investigator using the International Myeloma Working Group (IMWG) response criteria.~SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required." (NCT02272803)
Timeframe: From first dose until documented response, up to approximately 72 months
| Intervention | Percentage of participants (Number) |
|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | 92.5 |
| Arm B: Lenalidomide + Dexamethasone | 73.8 |
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the date of the first documented tumor progression, as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria, or to death due to any cause, provided death does not occur more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical deterioration will not be considered progression. (NCT02272803)
Timeframe: From randomization to the date of first documented tumor progression or death due to any cause, up to approximately 72 months
| Intervention | Months (Median) |
|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | NA |
| Arm B: Lenalidomide + Dexamethasone | 43.33 |
Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld)
"ORR is the proportion of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or PR as determined by investigator using the International Myeloma Working Group (IMWG) response criteria.~SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required." (NCT02272803)
Timeframe: From first dose until documented response (assessed up to February 2017, approximately 24 months)
| Intervention | Percentage of participants (Number) |
|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | 87.5 |
Progression Free Survival (PFS) Rate
PFS rate is defined as the percentage of participants who have neither progressed nor died at the specified timepoints (NCT02272803)
Timeframe: From randomization up to the specified timepoints, up to 3 years
| Intervention | Percentage of Participants (Number) |
|---|
| 1 year | 2 years | 3 years |
|---|
| Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608) | 0.87 | 0.67 | 0.61 |
,| Arm B: Lenalidomide + Dexamethasone | 0.89 | 0.60 | 0.56 |
Overall Survival
Time from initiation of therapy to death (NCT02279394)
Timeframe: From start of treatment up to +/- 60 months
| Intervention | months (Median) |
|---|
| Elo / Len / Dex | 50.5 |
| Elo / Len | 60.2 |
Time to Progression
Time from initiation of therapy to progression defined by the IMWG criteria. (NCT02279394)
Timeframe: From start of treatment up to +/- 60 months
| Intervention | months (Median) |
|---|
| Elo / Len / Dex | 56.1 |
| Elo / Len | 56.2 |
Percent of Patients Who Are Progression Free at 2 Years
Percent of patients who are alive and without documented progression after at least 2-years of follow-up. All patients who receive study treatment are assessed including those who have died or lost to follow-up prior to 2-years. Progression was defined as an increase in SPEP [25% and an absolute increase of 0.5g/d] or UPEP [25% and an absolute increase of 200mg/24hours] on 2 successive evaluations as determined by the IMWG response criteria or documented progression by the FreeLite progressive disease criteria in the absence of serum or urine involvement. (NCT02279394)
Timeframe: 2 Years
| Intervention | percentage of participants (Number) |
|---|
| Elo / Len / Dex | 45.0 |
| Elo / Len | 36.4 |
Objective Response Percent
Percent of patients with objective response defined as partial response or better based on the International Myeloma Working Group Response (IMWG) criteria (NCT02279394)
Timeframe: 2 Years from start of treatment
| Intervention | percentage of participants (Number) |
|---|
| Elo / Len / Dex | 82.5 |
| Elo / Len | 72.7 |
Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale
"The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms such as pain, itching, night sweats,trouble sleeping, fatigue and trouble concentrating and concerns regarding lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. All questions are answered on a 5-point scale ranging from not at all (0) to very much (4). The Additional Concerns subscale ranges from 0 to 60, where higher scores reflect better HRQoL." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 3.8 | 5.8 | 6.6 | 8.3 |
,| Placebo Plus R-CHOP | 4.1 | 5.2 | 4.5 | 6.5 |
K-M Estimate of Time to Next Lymphoma Therapy (TTNLT)
Time to next lymphoma therapy was defined as the time from randomization to the time of treatment change for the next lymphoma treatment. Participants without treatment change were censored at date last known alive. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as treatment change for the next lymphoma therapy if the decision to treat and the location to be treated were determined prior to randomization. (NCT02285062)
Timeframe: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
| Intervention | Months (Median) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | NA |
| Placebo Plus R-CHOP | NA |
Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire
The completion rate for FACT-Lym assessments was judged by looking at the number of completed FACT-Lym assessments at each time point. The FACT-Lym was considered completed if at least 1 calculable score was present. Completion rates were calculated as the number and percentage of participants out of the total number of patients in the ITT population and summarized by visit/cycle and treatment group. The FACT-Lym is a health related quality of life (HRQoL) questionnaire targeted to the management of chronic illness, predominantly within oncology and is considered an extension of the FACT-General questionnaire. (NCT02285062)
Timeframe: Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Percentage of Participants (Number) |
|---|
| Screening | Midcycle = After Cycle 3, but before Cycle 4 | End of Treatment (EoT) = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 98.6 | 87.0 | 76.1 | 67.7 |
,| Placebo Plus R-CHOP | 98.2 | 86.3 | 79.6 | 69.5 |
Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS)
"The EQ-5D-3L questionnaire includes a visual analogue scale which records the respondent's self-rated health on a vertical, 0-100 scale where 100 = Best imaginable health state and 0 = Worst imaginable health state. Higher scores again indicate better HRQoL and positive change scores indicate that post screening values were higher than those observed at screening. The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to no problems, some problems and extreme problems." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 4.0 | 6.0 | 8.0 | 12.0 |
,| Placebo Plus R-CHOP | 3.0 | 9.0 | 6.0 | 9 |
K-M Estimate of Overall Survival (OS)
Overall survival was assessed by the Independent Response Adjudication Committee (IRAC) and defined as time from randomization until death due to any cause. Participants who withdrew consent were censored at the time of withdrawal. Participants who were still alive before the clinical data cutoff date and participants who were lost to follow-up were censored at date last known alive. (NCT02285062)
Timeframe: From randomization until death due to any cause (up to approximately 86 months)
| Intervention | Months (Median) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | NA |
| Placebo Plus R-CHOP | NA |
K-M Estimate of Duration of Complete Response
Duration of complete response was calculated for complete responders only and was defined as the time from documented initial complete response prior to initiation of subsequent systemic antilymphoma therapy until documented disease progression or death, whichever occurred earlier. Participants who had not progressed or died at the time of the analysis were censored at the date of last response assessment demonstrating no disease progression. Participants who changed treatment without evidence of disease progression were censored at the last assessment showing no progression prior to treatment change. (NCT02285062)
Timeframe: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months.
| Intervention | Months (Median) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | NA |
| Placebo Plus R-CHOP | NA |
Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale
"The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from not at all (0) to very much (4). The physical well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | -0.7 | -0.0 | 1.5 | 2.8 |
,| Placebo Plus R-CHOP | 0.2 | 0.9 | 0.7 | 2.6 |
Percentage of Participants Who Achieved an Objective Response
An objective response = percentage of participants who achieved a complete response or partial response after initiation of the treatment and prior to initiation of subsequent systemic anti-lymphoma therapy. A CR = complete metabolic response; Target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in other nodes, liver, or spleen. Splenic nodules regressed by ≥ 50% in their SPD or for single nodules, in the greatest transverse diameter; no new lesions. Participants who did not have any adequate response assessments during this period were not considered as responders. (NCT02285062)
Timeframe: From randomization date up to the data cut off date of 15 March 2019; median total treatment duration was 18.10 weeks for both treatment arms; range = 1.6 to 29.0 weeks for R2-CHOP arm and 0.3 to 22.9 weeks for placebo-R-CHOP arm
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 90.9 |
| Placebo Plus R-CHOP | 90.9 |
Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score
"The EQ-5D-3L is a generic, self-reported preference-based measure of health across five dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has three levels of 'severity' corresponding to no problems, some problems and extreme problems. The instrument is scored as a single summary index using one of the available EQ-5D-3L value sets; in this study the UK scoring weights 9 were used. The UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health (-0.594 is considered 'worse than death')." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 0.08 | 0.10 | 0.10 | 0.15 |
,| Placebo Plus R-CHOP | 0.08 | 0.14 | 0.06 | 0.09 |
Percentage of Participants Who Achieved a Complete Response (CR)
The percentage of participants who achieved a CR after initiation of the study treatment and prior to initiation of subsequent systemic antilymphoma therapy as assessed by the IRAC. A CR = complete metabolic response; target nodes/nodal masses regressed on computed tomography to (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy. Regressed to normal size by imaging, and absence of nodules related to lymphoma. If bone marrow was involved prior to therapy, no evidence of fluorodeoxyglucose avid disease in marrow per International Working Group (IWG) 2014 for Non-Hodgkin's Lymphoma (NHL). Participants who did not have any adequate response assessments during this period were not considered as responders. (NCT02285062)
Timeframe: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 69.1 |
| Placebo Plus R-CHOP | 64.9 |
Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI)
"The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from not at all (0) to very much (4). The FACT-Lym TOI is calculated by summing the Physical Well-being, Functional Well-being and Additional Concerns scores and has a range of 0 to 116. Higher scores reflect better HRQoL or fewer symptoms." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | 2.6 | 5.9 | 9.1 | 13.5 |
,| Placebo Plus R-CHOP | 4.6 | 7.5 | 5.8 | 12.2 |
Kaplan-Meier Estimate of Progression Free Survival (PFS)
Progression free survival was defined as the time (months) from the date of randomization to the date of disease progression or death (any cause), whichever occurred earlier and was assessed by the Independent Response Adjudication Committee (IRAC). Relapse from complete response (CR) was considered as disease progression throughout the study. Disease progression was determined based on the Revised Response Criteria for Malignant Lymphoma. The PFS analysis was based on the censoring rules using the Food and Drug Administration (FDA) Guidance. Participants who did not experience disease progression and who did not die before the clinical data cutoff date were censored at the date of last adequate response assessment. (NCT02285062)
Timeframe: From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months
| Intervention | months (Median) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | NA |
| Placebo Plus R-CHOP | NA |
Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS)
EFS was defined as the time (months) from randomization until occurrence of one of the following events, whichever occurred first: • Disease progression • Initiation of subsequent systemic anti-lymphoma therapy • Death due to any cause The assessment of EFS was conducted by the IRAC using the International Working Group (IWG) criteria for NHL. Pre-specified optional therapies such as the extra 2 doses of single agent rituximab after Cycle 6 or consolidation radiotherapy did not count as an EFS event (initiation of subsequent systemic anti-lymphoma therapy) if the decision to treat and the location to be treated was determined prior to randomization. Participants who did not experience any of the events defined in the categories above before the clinical data cutoff date were censored at date last known alive. (NCT02285062)
Timeframe: From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
| Intervention | Months (Median) |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | NA |
| Placebo Plus R-CHOP | NA |
Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale
"The FACT-Lym questionnaire is a validated instrument for assessing the impact of lymphoma on HRQL and contains 42 questions covering HRQL and common lymphoma symptoms and treatment side-effects. It begins with the Functional Assessment of Cancer Therapy - General (FACT-G), which contains 27 questions covering four core subscales: Physical Wellbeing (7 items), Social/Family Wellbeing (7), Emotional Wellbeing (6), and Functional Wellbeing (7). The FACT-Lym also includes an Additional Concerns subscale (15 questions) used to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from not at all (0) to very much (4). The functional well-being subscale ranges from 0 to 28, where higher scores reflect better HRQoL." (NCT02285062)
Timeframe: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
| Intervention | Units on a Scale (Mean) |
|---|
| Midcycle | C6 D1 | EoT = 3-4 weeks after C6 | Follow-Up Period: Week 34 |
|---|
| Lenalidomide Plus R-CHOP (R2-CHOP) | -0.5 | 0.0 | 1.0 | 2.3 |
,| Placebo Plus R-CHOP | 0.5 | 1.4 | 0.7 | 3.1 |
Proportion of Participants With Successful Response
"Rate of response to pneumococcal 13-valent conjugate vaccine defined as a four-fold rise from baseline to 28 days after immunization (day 43) for >= 2 of the 3 serotypes studied by OPA of antibodies from sera.~The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation." (NCT02309515)
Timeframe: Day 43
| Intervention | proportion of participants (Number) |
|---|
| Arm I (Lenalidomide, Pneumococcal 13-valent Conjugate Vaccine) | 0.2 |
| Arm II (Pneumococcal 13-valent Conjugate Vaccine) | 0.0 |
Percentage of Participants With Event-free Survival (EFS)
This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Event-free survival is defined as survival without disease progression, second primary malignancy, and death. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate event-free survival during the 5 year post-randomization follow-up period. (NCT02322320)
Timeframe: 5 years post-randomization in BMT CTN 0702
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 44.2 |
| RVD Consolidation | 42.1 |
| Lenalidomide Maintenance | 42.4 |
Percentage of Participants With Secondary Primary Malignancies (SPM)
"This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). SPM is defined as development of any second malignancy, excluding non-melanoma skin cancers. To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of SPM during the 5 year post-randomization follow-up period.~The development of any SPMs excludes non-melanoma skin cancers. Death without SPMs will be considered a competing risk for this event. The cumulative incidence of SPMs will be compared between treatment arms." (NCT02322320)
Timeframe: 5 years post-randomization in BMT CTN 0702
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 10.8 |
| RVD Consolidation | 7.9 |
| Lenalidomide Maintenance | 7.2 |
Percentage of Participants With Progression-free Survival (PFS)
This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate progression-free survival during the 5 year post-randomization follow-up period. (NCT02322320)
Timeframe: 5 years post-randomization in BMT CTN 0702
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 47.7 |
| RVD Consolidation | 44.1 |
| Lenalidomide Maintenance | 45.0 |
Percentage of Participants With Overall Survival (OS)
This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Overall survival is defined as survival of death from any cause. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate overall survival during the 5 year post-randomization follow-up period. (NCT02322320)
Timeframe: 5 years post-randomization in BMT CTN 0702
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 74.7 |
| RVD Consolidation | 75.4 |
| Lenalidomide Maintenance | 76.4 |
Percentage of Participants With Disease Progression
"This analysis includes all randomized subjects from BMT CTN 0702, classified by their treatment assignment (intention-to-treat). Disease progression is defined as progression of multiple myeloma, including one or more of the following:~Reappearance of serum monoclonal paraprotein at a level >= 0.5 g/dL~24-hour urine protein electrophoresis of at least 200mg paraprotein/24 hours~Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in serum and urine~At least 10% plasma cells in a bone marrow aspirate or trephine biopsy~Definite increase in the size of existing bone lesions or soft tissue plasmacytomas~Development of new bone lesions or soft tissue plasmacytomas~Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to other causes~To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of progression during the follow-up period." (NCT02322320)
Timeframe: 5 years post-randomization in BMT CTN 0702
| Intervention | percentage of participants (Number) |
|---|
| Tandem Auto Transplant | 48.8 |
| RVD Consolidation | 54.3 |
| Lenalidomide Maintenance | 54.2 |
The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years
"Progression is defined as an increase of ≥ 25% from the lowest response value in any one or more of the following:~Serum M-component with an absolute increase ≥ 0.5 g/dL; and/or Urine M-component with an absolute increase ≥ 200 mg/24 hours; and/or Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100mg/l) Bone marrow plasma cell percentage (absolute % must be ≥10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum calcium >11.5mg/100ml) that can be attributed solely to the plasma cell proliferative disorder" (NCT02331368)
Timeframe: 2 Years
| Intervention | percentage of patients (Number) |
|---|
| Anti-PD-1 (MK-3475) | 83 |
The Estimated Percentage of Patients Alive at 2 Years
(NCT02331368)
Timeframe: 2 Years
| Intervention | percentage of patients (Number) |
|---|
| Anti-PD-1 (MK-3475) | 100 |
The Number of Patients That Achieve Complete Response
The primary efficacy endpoint is complete response rate. The complete response rate was estimated by the observed proportion of complete responders at day 180. Complete response (CR) was defined as negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow and negative bone marrow flow cytometry. (NCT02331368)
Timeframe: 180 days post-transplant
| Intervention | Participants (Count of Participants) |
|---|
| Anti-PD-1 (MK-3475) | 7 |
Change From Baseline in Hemoglobin Levels
(NCT02335983)
Timeframe: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
| Intervention | g/L (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 1 Day 8 | Change from Baseline to Cycle 1 Day 15 | Change from Baseline to Cycle 2 Day 1 | Change from Baseline to Cycle 2 Day 8 | Change from Baseline to Cycle 2 Day 15 |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 111.50 | -1.25 | -1.75 | -3.75 | -0.13 | 0.00 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 113.21 | -1.82 | -5.64 | 2.19 | 4.19 | 2.97 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 120.00 | -5.56 | -6.50 | -3.29 | -2.86 | -5.14 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 116.90 | -1.50 | -6.90 | -5.70 | -6.00 | -8.50 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 120.67 | -3.33 | -9.50 | -9.25 | -8.17 | -11.33 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 123.24 | -0.91 | -5.10 | -7.38 | -5.59 | -8.45 |
Change From Baseline in Neutrophil Count
(NCT02335983)
Timeframe: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
| Intervention | 10^9 cells/L (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 1 Day 8 | Change from Baseline to Cycle 1 Day 15 | Change from Baseline to Cycle 2 Day 1 | Change from Baseline to Cycle 2 Day 8 | Change from Baseline to Cycle 2 Day 15 |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 3.04 | 0.59 | 1.08 | 0.02 | 0.57 | 0.33 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 3.26 | 0.37 | 0.09 | 0.18 | 0.41 | 0.42 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 3.24 | -0.19 | 0.43 | 0.09 | 0.46 | 0.56 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 2.53 | 0.02 | 0.28 | 0.36 | 0.18 | -0.30 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 3.40 | 0.03 | -0.09 | -0.33 | -0.67 | -0.54 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 2.72 | 0.97 | 0.81 | 0.16 | 0.63 | -0.06 |
Change From Baseline in Platelet Count
(NCT02335983)
Timeframe: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
| Intervention | 10^9 cells/L (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 1 Day 8 | Change from Baseline to Cycle 1 Day 15 | Change from Baseline to Cycle 2 Day 1 | Change from Baseline to Cycle 2 Day 8 | Change from Baseline to Cycle 2 Day 15 |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 214.00 | 2.38 | -23.25 | 141.75 | -28.00 | -21.25 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 233.03 | -21.42 | -53.39 | 111.06 | -52.78 | -44.19 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 242.89 | -51.11 | -101.88 | 152.00 | -106.29 | -76.14 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 151.60 | -12.90 | -58.60 | 55.00 | -44.10 | -44.40 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 202.50 | -49.50 | -66.83 | 68.67 | -74.75 | -63.25 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 172.38 | -17.36 | -66.39 | 44.84 | -71.06 | -60.13 |
Number of Participants With Adverse Events (AEs)
"Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events.~An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment.~A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria:~fatal~life threatening~requires in-patient hospitalization or prolongation of existing hospitalization~results in persistent or significant disability/incapacity~congenital anomaly/birth defect~other medically important serious event~The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death." (NCT02335983)
Timeframe: From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
| Intervention | Participants (Count of Participants) |
|---|
| Any adverse event (AE) | AE Grade ≥ 3 | Serious adverse events | AEs leading to discontinuation of carfilzomib | AEs leading to discontinuation of lenalidomide | AEs leading to discontinuation of dexamethasone | Fatal adverse events | Treatment-related adverse events (TRAE) | Treatment-related AEs Grade ≥ 3 | Treatment-related serious adverse events | TRAEs leading to discontinuation of carfilzomib | TRAEs leading to discontinuation of lenalidomide | TRAEs leading to discontinuation of dexamethasone | Treatment-related fatal adverse events |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 9 | 5 | 3 | 0 | 0 | 0 | 0 | 9 | 5 | 1 | 0 | 0 | 0 | 0 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 33 | 21 | 11 | 1 | 2 | 2 | 0 | 32 | 18 | 8 | 1 | 2 | 2 | 0 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 9 | 6 | 3 | 2 | 2 | 2 | 0 | 9 | 5 | 3 | 2 | 2 | 2 | 0 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 10 | 7 | 4 | 1 | 1 | 1 | 0 | 9 | 6 | 1 | 1 | 1 | 1 | 0 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 12 | 9 | 5 | 2 | 2 | 2 | 0 | 11 | 8 | 2 | 1 | 1 | 1 | 0 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 34 | 23 | 10 | 5 | 5 | 5 | 2 | 30 | 18 | 6 | 5 | 5 | 5 | 2 |
Change From Baseline in Bilirubin
(NCT02335983)
Timeframe: Baseline and Cycle 2 day 1
| Intervention | µmol/L (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 2 Day 1 |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 10.26 | 3.42 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 7.16 | 1.21 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 6.84 | 0.49 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 8.55 | 0.86 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 9.98 | 1.00 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 9.10 | 1.34 |
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
(NCT02335983)
Timeframe: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
| Intervention | hours (Median) |
|---|
| Carfilzomib 56 mg/m² | 0.28 |
| Carfilzomib 70 mg/m² | 0.27 |
Progression-free Survival (PFS)
"PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause.~Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia.~PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment." (NCT02335983)
Timeframe: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
| Intervention | months (Median) |
|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | NA |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | NA |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | NA |
| RRMM: Combined Carfilzomib 70 mg/m² | NA |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | NA |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | NA |
| NDMM: Combined Carfilzomib 70 mg/m² | NA |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | NA |
Overall Response Rate (ORR)
"Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy.~Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation." (NCT02335983)
Timeframe: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
| Intervention | percentage of participants (Number) |
|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 90.0 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 91.7 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 88.2 |
| RRMM: Combined Carfilzomib 70 mg/m² | 89.1 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 88.9 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 77.8 |
| NDMM: Combined Carfilzomib 70 mg/m² | 83.3 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 97.0 |
Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
(NCT02335983)
Timeframe: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
| Intervention | ng/mL (Mean) |
|---|
| Carfilzomib 56 mg/m² | 11700 |
| Carfilzomib 70 mg/m² | 12400 |
Change From Baseline in Creatinine
(NCT02335983)
Timeframe: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
| Intervention | µmol/L (Mean) |
|---|
| Baseline | Change from Baseline to Cycle 1 Day 8 | Change from Baseline to Cycle 1 Day 15 | Change from Baseline to Cycle 2 Day 1 | Change from Baseline to Cycle 2 Day 8 | Change from Baseline to Cycle 2 Day 15 |
|---|
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 75.80 | -1.22 | 3.65 | -10.39 | -12.27 | -12.38 |
,| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 80.60 | -0.22 | 0.42 | -4.31 | -4.32 | -1.99 |
,| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 95.37 | -8.51 | 29.39 | -17.17 | -20.08 | -21.85 |
,| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 80.18 | -2.65 | -4.42 | -3.80 | -6.45 | -6.28 |
,| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 82.88 | -5.30 | -4.60 | -7.74 | -11.09 | -13.26 |
,| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 79.09 | 2.09 | -1.85 | -1.44 | 1.85 | 4.88 |
Duration of Response (DOR)
Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment. (NCT02335983)
Timeframe: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
| Intervention | months (Median) |
|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | NA |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | NA |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | NA |
| RRMM: Combined Carfilzomib 70 mg/m² | NA |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | NA |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | NA |
| NDMM: Combined Carfilzomib 70 mg/m² | NA |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | NA |
Complete Response Rate (CRR)
"Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).~sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, < 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC." (NCT02335983)
Timeframe: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
| Intervention | percentage of participants (Number) |
|---|
| RRMM Dose-evaluation: Carfilzomib 56 mg/m² | 20.0 |
| RRMM Dose-evaluation: Carfilzomib 70 mg/m² | 16.7 |
| RRMM Dose-expansion: Carfilzomib 70 mg/m² | 26.5 |
| RRMM: Combined Carfilzomib 70 mg/m² | 23.9 |
| NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² | 22.2 |
| NDMM Dose-expansion: Carfilzomib 70 mg/m² | 11.1 |
| NDMM: Combined Carfilzomib 70 mg/m² | 16.7 |
| NDMM Dose-expansion: Carfilzomib 56 mg/m² | 33.3 |
Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
(NCT02335983)
Timeframe: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
| Intervention | hr*ng/mL (Mean) |
|---|
| Carfilzomib 56 mg/m² | 4150 |
| Carfilzomib 70 mg/m² | 9130 |
Grade 3 and 4 Treatment-Emergent Adverse Event (TEAE) Rate
Grade 3 and 4 TEA rate was defined as the proportion of participants who experienced a grade 3 or 4 adverse event of any attribution based on NCI Common Toxicity Criteria for Adverse Events Version 4 (CTCAEv4) on treatment. (NCT02375555)
Timeframe: The adverse event observation period defined as the time on treatment (+30d) is 278 weeks.
| Intervention | proportion of participants (Number) |
|---|
| Elotuzumab, Lenalidomide, Bortezomib, and Dexamethasone | 0.70 |
4 Cycle Response Rate
Disease response was defined as the proportion of patients who achieved a response of partial response or better using International Myeloma Working Group (IMWG) response criteria. Partial Response (PR) defined as 50% reduction of serum M-protein and reduction in 24h urinary M-protein by ≥90% or to <200mg/24h; Very Good Partial Response (VGPR) defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100mg/24h; Complete Response (CR) defined as negative immunofixation on serum and urine and, disappearance of any soft tissue plasmacytomas and, <5% plasma cells in BM; Stringent Complete Response (sCR) defined as normal FLC ratio and absence of clonal cells in BM by immunohistochemistry or 2-4 color flow cytometry. The Clopper and Pearson method was used to estimate the 95% CIs for the response rate at Week 12. (NCT02375555)
Timeframe: Participants were followed up to 12 weeks.
| Intervention | proportion of participants (Number) |
|---|
| Elotuzumab, Lenalidomide, Bortezomib, and Dexamethasone | 0.971 |
Successful Stem Cell Mobilization (SC Mob) Rate
Successful SC Mob defined as the proportion of participants with the ability to collect a total of at least 2*10^6 CD34+ cells/kg. (NCT02375555)
Timeframe: The most distant time of stem cell mobilization from time of registration is 21.4 weeks with a median of 15.14 weeks.
| Intervention | proportion of participants (Number) |
|---|
| Elotuzumab, Lenalidomide, Bortezomib, and Dexamethasone | 0.968 |
Objective Response Rate (ORR) at End of 8 Cycles of Induction Therapy.
ORR was defined as the proportion of patients who achieved a disease response of partial response (PR) or better using IMWG response criteria. PR defined as 50% reduction of serum M-protein and reduction in 24h urinary M-protein by ≥90% or to <200mg/24h; Very Good Partial Response (VGPR) defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100mg/24h; Complete Response (CR) defined as negative immunofixation on serum and urine and, disappearance of any soft tissue plasmacytomas and, <5% plasma cells in BM; Stringent Complete Response (sCR) defined as normal FLC ratio and absence of clonal cells in BM by immunohistochemistry or 2-4 color flow cytometry. (NCT02375555)
Timeframe: Participants were followed up to 24 weeks.
| Intervention | proportion of participants (Number) |
|---|
| All Patients Treated With E-RVD. | 0.950 |
4 Cycle Ever Dose Modification (DM) Rate
The 4 cycle ever DM rate is the proportion of participants who started therapy and required dose modification of any study drug during the first four cycles of E-RVD. (NCT02375555)
Timeframe: Participants were followed up to 12 weeks.
| Intervention | proportion of participants (Number) |
|---|
| Elotuzumab, Lenalidomide, Bortezomib, and Dexamethasone | .40 |
Time to Progression (TTP) by IRC Evaluation
TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma. (NCT02399085)
Timeframe: Approximately 2.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 16.2 |
Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs)
TEAEs are defined as any adverse event reported in the following time interval (including the lower and upper limits): date of first administration of study treatment; date of last administration of study treatment + 30 days, or if they are considered to be related to the study drug. (NCT02399085)
Timeframe: Approximately 6.5 years after first participant enrolled
| Intervention | Participants (Count of Participants) |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 81 |
Disease Control Rate (DCR) by IRC Evaluation
DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study. (NCT02399085)
Timeframe: Approximately 2.5 years after first participant enrolled
| Intervention | Participants (Count of Participants) |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 59 |
DCR by INV Evaluation
DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study. (NCT02399085)
Timeframe: Approximately 2.5 years after first participant enrolled
| Intervention | Participants (Count of Participants) |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 60 |
Duration of Response (DoR) by IRC Evaluation
DoR [months] = (date of assessment of tumor progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Treatment (MOR00208, Lenalidomide) | 43.9 | NA |
Time to Next Treatment (TTNT)
Kaplan-Meier analysis of TTNT in FAS population. TTNT is defined as the time from the first administration of any study drug to the institution of next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity and participant preference) or death of any cause, whatever comes first. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 12.1 | 12.5 |
Serum Drug Levels of MOR00208
"The pharmacokinetics (PK) profile of MOR00208 was investigated by quantifying serum drug levels at baseline and after repeated IV administrations for up to 24 treatment cycles using sparse sampling.~MOR00208 PK sample was taken pre-dose and 1 hour ± 10 min after the end of MOR00208 infusion for Cycle 1 to Cycle 23. MOR00208 PK sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21, 23)." (NCT02399085)
Timeframe: Cycle 1 Days 1, 4, 15 predose and 1 hr post-dose; Cycle 2 Days 1, 15 predose and 1 hr post-dose; Cycle 3 Days 1, 15 predose and 1 hr post-dose; Cycles 4, 5, 6, 7, 9, 11,13, 15, 17, 19, 21, 23 Day 1 predose; End of Treatment
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 Day 1 (Predose) | Cycle 1 Day 1 (1 hour post dose) | Cycle 1 Day 4 (pre-dose) | Cycle 1 Day 4 (1 hour post-dose) | Cycle 1 Day 15 (pre dose) | Cycle 1 Day 15 (1 hour post-dose) | Cycle 2 Day 1 (predose) | Cycle 2 Day 1 (1 hour post-dose) | Cycle 2 Day 15 (Pre Dose) | Cycle 2 Day 15 (1 hour post-dose) ) | Cycle 3 Day 1 (predose) | Cycle 3 Day 1 (1 hour post-dose) | Cycle 3 Day 15 (predose) | Cycle 3 Day 15 (1 hour post-dose) | Cycle 4 Day 1 (predose) ) | Cycle 5 Day 1 (pre dose) | Cycle 6 Day 1 (pre dose) | Cycle 7 Day 1 (pre dose) | Cycle 9 Day 1 (pre dose) | Cycle 11 Day 1 (pre dose) | Cycle 13 Day 1 (pre dose) | Cycle 15 Day 1 (pre dose) | Cycle 17 Day 1 (pre dose) | Cycle 19 Day 1 (pre dose) | Cycle 21 Day 1 (pre dose) | Cycle 23 Day 1 (pre dose) | End of Treatment |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 6.7 | 249075.9 | 126306.8 | 363626.2 | 157722.3 | 396262.1 | 181870.8 | 439788.2 | 217846.9 | 442940.2 | 208520.6 | 466135.8 | 223909.4 | 455635.0 | 216328.4 | 142134.4 | 115132.3 | 114661.5 | 108640.4 | 126472.0 | 100853.5 | 159676.5 | 175855.1 | 197045.0 | 197228.0 | 224253.3 | 141240.7 |
Progression-free Survival (PFS) by IRC Evaluation
PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 11.6 | 11.6 |
PFS by INV Evaluation
PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 9.1 | 9.1 |
Overall Survival (OS)
OS was defined as the time from the date of the first administration of any study drug until death from any cause (documented by the date of death). (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 33.5 | 33.5 |
Number of Participants With Best Objective Response Rate (ORR)
"ORR = complete response [CR] + partial response [PR]; Independent Radiology/Clinical Review Committee (IRC) Evaluation.~ORR after MOR00208 and Lenalidomide combination therapy assessed by the IRC evaluation.~ORR was defined as the number of participants of the total number of participants treated with MOR00208 + LEN with CR or PR as best response achieved at any time during the study." (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Participants (Count of Participants) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Treatment (MOR00208, Lenalidomide) | 46 | 46 |
Event-free Survival (EFS) by IRC Evaluation
EFS is defined as the time (in months) from the date of the first administration of any study drug to the date of tumour progression, first initiation of a new non-study anti-neoplastic therapy or death from any cause whichever comes first. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 8.7 | 9.1 |
DoR by Investigator (INV) Evaluation
DoR [months] = (date of assessment of tumour progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375. (NCT02399085)
Timeframe: Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Approximately 4.5 years after first participant enrolled | Approximately 6.5 years after first participant enrolled |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 43.9 | 43.4 |
TTP by INV Evaluation
TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma. (NCT02399085)
Timeframe: Approximately 2.5 years after first participant enrolled
| Intervention | Months (Median) |
|---|
| Tafasitamab (MOR00208) + Lenalidomide (LEN) | 14.1 |
Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization
Efficacy will be assessed monthly during NKAE treatment (4 months) by peripheral blood monoclonal protein monitoring. During follow-up, efficacy will be evaluated monthly the first 6 months. After that, quarterly until one year of follow-up. (NCT02481934)
Timeframe: 16 months
| Intervention | participants (Number) |
|---|
| NKAE Cells Infusion + Chemotherapy | 5 |
Number of Participants With Adverse Events During NKAE Treatment
Toxicity will be assessed by adverse events count during NKAE treatment monitoring peripheral blood absolute neutrophil count (cells/μl). Toxicity will be evaluated monthly during NKAE treatment (4 months). During follow-up, it will be assessed monthly the first 6 months. After that, quarterly until one year of follow-up, based on Common Toxicity Criteria for Adverse Events of the National Cancer Institute (CTCAE) to v.4.03. (NCT02481934)
Timeframe: 16 months
| Intervention | participants (Number) |
|---|
| NKAE Cells Infusion + Chemotherapy | 2 |
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
Number of participants experiencing a dose-limiting toxicity (DLT) is reported below. Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. (NCT02492750)
Timeframe: 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I - Dose Level 1 | 0 |
| Phase I - Dose Level 2 | 0 |
| Phase I - Dose Level 3 | 0 |
Survival Duration Without Disease Progression
Calculate rate of progression-free survival for subjects following treatment BiRd regimen compared to Rd treatment regimen. Progression is determined by the International Myeloma Working Group Criteria. (NCT02516696)
Timeframe: Until disease progression or death from any cause, for a maximum of approximately 5 years
| Intervention | days (Median) |
|---|
| BiRD Treatment Regimen | 661 |
| Rd Treatment Regimen | 1694 |
Overall Survival
Survival following treatment to the date of death of subjects on BiRd regimen as compared to Rd. (NCT02516696)
Timeframe: 4 years
| Intervention | days (Median) |
|---|
| BiRD Treatment Regimen | NA |
| Rd Treatment Regimen | 1014 |
Overall Response Rate
Capture the number of subjects who demonstrate a complete or partial response to treatment with BiRD regimen, as compared to Rd. Complete and partial responses are defined by the International Myeloma Working Group Criteria. (NCT02516696)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| BiRD Treatment Regimen | 7 |
| Rd Treatment Regimen | 4 |
Number of Patients With Objective Response Rate (CR+PR)
(NCT02516696)
Timeframe: up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| BiRD Treatment Regimen | 7 |
| Rd Treatment Regimen | 4 |
Number of Patients With Complete Response Rate (CR)
Complete response is defined by the International Myeloma Working Group Criteria. (NCT02516696)
Timeframe: up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| BiRD Treatment Regimen | 2 |
| Rd Treatment Regimen | 0 |
Number of Days for Event-Free Survival
Descriptively presented for each treatment group and no formal statistical comparison will be made between treatment arms (NCT02516696)
Timeframe: approximately 5 years
| Intervention | days (Median) |
|---|
| BiRD Treatment Regimen | 336 |
| Rd Treatment Regimen | 821 |
Number of Days for Duration of Response
Descriptively presented for each treatment group and no formal statistical comparison will be made between treatment arms (NCT02516696)
Timeframe: up to 3 years
| Intervention | days (Median) |
|---|
| BiRD Treatment Regimen | 308 |
| Rd Treatment Regimen | 803 |
Number of Days After Initiating Treatment With BiRd Regimen to Disease Progression, as Compared to Subjects on Rd Treatment Regimen.
Progression is determined by the International Myeloma Working Group Criteria. (NCT02516696)
Timeframe: Until disease progression for a maximum of approximately 5 years
| Intervention | days (Median) |
|---|
| BiRD Treatment Regimen | 661 |
| Rd Treatment Regimen | 1694 |
Number of Adverse Events Experienced
Capture the number of adverse events experienced with BiRd regimen as compared to Rd regimen (NCT02516696)
Timeframe: 2 years
| Intervention | adverse events (Number) |
|---|
| BiRD Treatment Regimen | 79 |
| Rd Treatment Regimen | 67 |
Functional Assessment of Chronic Illness Therapy - Fatigue Subscale (FS; Version 4) Score of Patients Receiving BiRd vs Rd Treatment
"The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) is a 40-item measure that assesses self-reported fatigue and its impact upon daily activities and function. The FACIT- Fatigue Subscore (FS) is comprised of 13 items, within the total 40-item FACIT-F, that assess fatigue and its impact. This analysis is only based on the FS score. Items are scored on a 5 point Likert-type scale. Item scores can range from 0 (not at all) to 4 (very much), and the total, summed score from 0 to 52; lower scores indicate greater fatigue. The recall period for each item is the past 7 days. Data is descriptively presented for each treatment group and no formal statistical comparison will be made between treatment arms." (NCT02516696)
Timeframe: up to 3 years
| Intervention | Score on a scale (Mean) |
|---|
| BiRD Treatment Regimen | 32.75 |
| Rd Treatment Regimen | 37.24 |
Apparent Total Clearance (CL/F) of Lenalidomide
Apparent volume of distribution, calculated as [(CL/F)/λz]. (NCT02538965)
Timeframe: Pharmacokinetic sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | ml/min (Geometric Mean) |
|---|
| Lenalidomide | 172.09 |
Apparent Volume of Distribution (Vz/F) of Lenalidomide
Apparent volume of distribution, calculated as [(CL/F)/λz]. (NCT02538965)
Timeframe: Pharmacokinetic sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | Liters (Geometric Mean) |
|---|
| Lenalidomide | 34.42 |
Area Under the Plasma Concentration Time Curve From 0 Extrapolated to Infinity (AUC-inf, AUC0∞) Of Lenalidomide
Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. (NCT02538965)
Timeframe: Pharmacokinetic sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Lenalidomide | 5656.67 |
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Lenalidomide (AUC-t)
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. (NCT02538965)
Timeframe: Pharmacokinetic (PK) sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Lenalidomide | 5378.83 |
Number of Participants Who Achieved a Best Response of Morphologic Complete Remission, Morphologic Complete Remission Incomplete or Partial Remission
"Overall response rate was defined as the number of participants with best response of CR, CRi or PR.~A CR was defined as:~ANC ≥ 1000/μL and platelets ≥ 100,000 without transfusions and/or exogenous growth factor support (no transfusion or exogenous growth factor within 7 days of assessment);~BM < 5% blasts evidence of trilineage hematopoiesis;~No evidence of extramedullary disease.~A CRi was defined as:~ANC < 1000/μL and platelets < 100,000/μL or > 100,000/μL without platelet recovery (requiring transfusion within 7 days of assessment);~BM with < 5% blasts and evidence of trilineage hematopoiesis;~No evidence of extramedullary disease.~A PR was defined as:~ANC of ≥ 1000/μL and platelets ≥ 100,000 without transfusions and/or exogenous growth factor support (no transfusion or exogenous growth factor within 7 days of assessment);~BM with 5% to 25% blasts and at least a 50% decrease in BM blast percent from baseline;~No evidence of extramedullary disease." (NCT02538965)
Timeframe: Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3.
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide | 1 |
Maximum Observed Concentration (Cmax) of Lenalidomide
Maximum observed plasma concentration, obtained directly from the observed concentration versus time data. (NCT02538965)
Timeframe: PK sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Lenalidomide | 1252.08 |
Number of Participants Who Achieved a Morphologic Complete Response Within the First Four Cycles of Lenalidomide Treatment According to the Modified International Working Group (IWG) Criteria
"The morphological complete response rate was defined as the total number of participants with morphological CR observed within the first 4 cycles of lenalidomide (regardless of whether the CR/CRi was observed at the end of Cycle 1, 2, 3 or 4) over the total number of participants evaluable for this endpoint. According to Modified IWG criteria, morphologic CR was defined as:~Absolute neutrophil count (ANC) ≥ 1000/μL and platelets ≥ 100,000 without transfusions and/or exogenous growth factor support (i.e., no transfusion or exogenous growth factor within 7 days of assessment;~Bone marrow < 5% blasts evidence of trilineage hematopoiesis;~No evidence of extramedullary disease.~Morphologic CRi was defined as:~ANC < 1000/μL and platelets < 100,000/μL or > 100,000/μL without platelet recovery (requiring transfusion within 7 days of assessment);~BM with < 5% blasts and evidence of trilineage hematopoiesis;~No evidence of extramedullary disease." (NCT02538965)
Timeframe: From day of the first dose of IP to end of cycle 4; Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3, and 4 and at treatment discontinuation.
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide | 1 |
Percentage of Participants With of Graft Versus Host Disease (GVHD)
Acute graft versus host disease generally occurs after allogeneic hematopoietic stem cell transplantation. It is a reaction of donor immune cells against host tissues. The 3 main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract. Chronic GVHD is scored per the National Institute of Health consensus conference grading system. Clinical manifestations of chronic GVHD include skin involvement resembling lichen planus or the cutaneous manifestations of scleroderma; dry oral mucosa with ulcerations and sclerosis of the gastrointestinal tract; and a rising serum bilirubin concentration. (NCT02538965)
Timeframe: From the first dose of study drug to 28 days after the last dose of study drug; up to data cut off date of 31 December 2017; maximum treatment was 12 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Lenalidomide | 0 |
Terminal Half-Life (t1/2) of Lenalidomide
Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. Terminal half-life was only calculated when a reliable estimate for λz could be obtained. (NCT02538965)
Timeframe: Pharmacokinetic sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | hours (Geometric Mean) |
|---|
| Lenalidomide | 2.311 |
Time to Reach Maximum Concentration (Tmax) of Lenalidomide
Time to cmax was obtained directly from the observed concentration versus time data. (NCT02538965)
Timeframe: Pk sampling was conducted after lenalidomide administration at Cycle 1 and was weight dependent at these timepoints: 0.5, 1, 2, 4, 6, 8 and 24 hours. The 24 hour PK sample was taken prior to the lenalidomide dose on Day 2.
| Intervention | Hours (Median) |
|---|
| Lenalidomide | 2.000 |
Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAE)
A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of lenalidomide and within 28 days after the last dose. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.3 and based on the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. (NCT02538965)
Timeframe: From the first dose of study drug until 28 days after the last dose of study drug; up to data cut off date of 31 December 2017; maximum duration of treatment was 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any TEAE Related to Lenalidomide | Any Grade 3/4 TEAE | Any Grade 3/4 TEAE Related to Lenalidomide | Any Grade 5 TEAE | Any Serious TEAE | Any Serious TEAE Related to Lenalidomide | Any Serious TEAE Leading to Dose Discontinuation | Any TEAE Leading to Dose Discontinuation | Any TEAE Leading to Dose Reduction | Any TEAE Leading to Dose Interruption | Any TEAE Leading to Death |
|---|
| Lenalidomide | 17 | 15 | 17 | 11 | 1 | 13 | 5 | 3 | 3 | 4 | 7 | 1 |
Number of Participants Who Received a Haematopoietic Stem Cell Transplant (HSCT)
The number of participants who had undergone a haematopoietic stem cell transplant was calculated over the total number of participants in the ITT population. Percentages were also calculated based on whether the transplantation was the first, second, or subsequent transplant post IP administration. (NCT02538965)
Timeframe: From first dose of study drug up to 5 years post HSCT
| Intervention | Participants (Count of Participants) |
|---|
| Any Transplant After Treatment Start | First Transplant After Treatment Start | Second Transplant After Treatment Start | Any Subsequent Transplant After Treatment Start |
|---|
| Lenalidomide | 2 | 2 | 0 | 0 |
Number of Participants With a Morphologic CR, CRi, PR or Treatment Failure at Cycles 1, 2 and 3
"Disease assessment outcome at the end of Cycles 1-3 based on Cheson criteria:~Morphologic CR =~ANC ≥ 1000/μL and platelet ≥ 100,000 without transfusions and/or exogenous growth factor support (no transfusion or exogenous growth factor within 7 days of assessment)~BM < 5% blasts evidence of trilineage hematopoiesis~No evidence of extramedullary disease Morphologic CRi =~1. ANC< 1000/μL and Platelets < 100,000/μL or > 100,000/μL without platelet recovery (requiring transfusion within 7 days of assessment) 2. BM with < 5% blasts and evidence of trilineage hematopoiesis 3. No evidence of extramedullary disease PR =~ANC ≥ 1000/μL and platelets ≥ 100,000 without transfusions and/or exogenous growth factor support~BM with < 5%-25% blasts and at least a 50% decrease in BM blast percent from baseline~No evidence of extramedullary disease Treatment Failure = resistant disease; survival ≥ 7 days post-therapy; failed to achieve CR, CRi, or PR but stable with persistent AML" (NCT02538965)
Timeframe: Response was assessed at the completion of the 21-day treatment period of cycles 1, 2, 3.
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 Morphologic CR | Cycle 1 Morphologic CRi | Cycle 1 PR | Cycle 1 Treatment Failure | Cycle 2 Morphologic CR | Cycle 2 Morphologic CRi | Cycle 2 PR | Cycle 2 Treatment Failure | Cycle 3 Morphologic CR | Cycle 3 Morphologic CRi | Cycle 3 PR | Cycle 3 Treatment Failure |
|---|
| Lenalidomide | 0 | 0 | 1 | 13 | 0 | 1 | 0 | 5 | 0 | 1 | 0 | 0 |
Number of Participants With Adverse Events Graded According to CTC (Phase II)
"The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence of maximum tolerated dose level of the Intent to treat (ITT) group of subjects is summarized.~39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group." (NCT02561273)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| grade 3,4 neutropenia | grade 3, 4 leukopenia | grade 3, 4 anemia | grade 3, 4 thrombocytopenia | grade 3, 4 lymphopenia | grade 3, 4 febrile neutropenia | grade 3, 4 diarrhea | grade 3, 4 Peripheral sensory neuropathy | grade 3, 4 fatigue | grade 3, 4 nausea | grade 3, 4 anorexia | grade 3, 4 vomiting | grade 3, 4 mucositis oral | grade 3, 4 Rash maculo-papular | grade 3, 4 hypotension | grade 3, 4 back pain |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 27 | 25 | 17 | 17 | 18 | 15 | 3 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I)
Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. (NCT02561273)
Timeframe: Up to 6 cycles of treatment (approximately 5 months)
| Intervention | Participants (Count of Participants) |
|---|
| grade 3,4 neutropenia | grade 3, 4 anemia | grade 3, 4 thrombocytopenia | grade 3,4 neutropenia fever | grade 3, 4 diarrhea | grade 3, 4 hyperglycemia | grade 3, 4 hypokalemia | grade 3, 4 hypotension | grade 3, 4 hyperbilirubinemia | grade 3, 4 mucositis | grade 3,4 nausea | grade 3,4 vomiting |
|---|
| 10 mg Lenalidomide Participants | 5 | 3 | 2 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| 15 mg Lenalidomide Participants | 4 | 3 | 3 | 0 | 2 | 2 | 1 | 1 | 1 | 2 | 2 | 1 |
Progression-free Survival
The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest. (NCT02561273)
Timeframe: Time from registration to progression or death due to any cause, assessed up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 55 |
Overall Survival
The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT02561273)
Timeframe: Time from registration to death due to any cause, assessed up to 1 year
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 89 |
Overall Response Rate
The ORR will be estimated by the total number of patients who achieve a PR or CR at the end of six cycles of treatment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true ORR will be calculated. (NCT02561273)
Timeframe: Up to the completion of course 6 (18 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 69 |
Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) within the first cycle of study treatment. (NCT02561273)
Timeframe: 21 days
| Intervention | milligrams (Number) |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 10 |
Complete Response Rate (Phase II)
A success is defined to be an objective status of CR after completion of 6 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A 95% confidence interval for the true overall CR rate will be calculated according to the method of Duffy and Santner. (NCT02561273)
Timeframe: Up to the completion of course 6 (18 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Combination Chemotherapy, Lenalidomide) | 49 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. OS was calculated from the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. This is an event-driven (events of death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). The database cutoff date was August 3, 2020. (NCT02579863)
Timeframe: Up to approximately 55 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | NA |
| Lenolidomide + Dexamethasone | NA |
Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020. (NCT02579863)
Timeframe: Up to approximately 55 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | 152 |
| Lenolidomide + Dexamethasone | 141 |
Number of Participants Discontinuing Study Treatment Due to an AE
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020. (NCT02579863)
Timeframe: Up to approximately 55 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | 44 |
| Lenolidomide + Dexamethasone | 26 |
Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review
Response duration was defined as the time from first documented evidence of at least a partial response (sCR+CR+VGPR+PR]), until confirmed disease progression or death. DOR was calculated from product-limit (Kaplan-Meier) method for censored data. This is an event-driven (events of disease progression and death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). Full Range is the minimum and maximum of the observed duration of response. The data cutoff date was July 9, 2018. (NCT02579863)
Timeframe: Up to approximately 30 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | NA |
| Lenolidomide + Dexamethasone | NA |
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Disease control rate was defined as the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, or have demonstrated SD for at least 12 weeks prior to any evidence of progression. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours; SD = not meeting the criteria for CR, VGPR, PR, or PD; PD = development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Data cutoff date was July 9, 2018. (NCT02579863)
Timeframe: Up to approximately 30 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | 89.1 |
| Lenolidomide + Dexamethasone | 91.6 |
Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review
PFS was defined as the time from randomization to the first documented disease progression (events of new bone lesions, soft tissue plasmacytomas or an increase in existing lesions, or death due to any cause). The median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. Due to the small number of events, the tail of the estimated survival distribution was close to the median for both arms. The higher variability of the tail estimates resulted in observing the median estimate in the experimental arm but not in the standard of care arm even when number of events in 2 arms were similar. The database cutoff date was July 9, 2018. (NCT02579863)
Timeframe: Up to approximately 30 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | 19.6 |
| Lenolidomide + Dexamethasone | NA |
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
ORR was based on participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018. (NCT02579863)
Timeframe: Up to approximately 30 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Lenalidomide + Dexamethasone | 74.4 |
| Lenolidomide + Dexamethasone | 68.8 |
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: From study start up to end of study (Up to a maximum of 69 months)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 100.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 97.4 |
Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT was defined as a complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 50.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 90.0 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 79.5 |
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
CR at EOI was assessed by IRC according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 66.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 60.0 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 38.5 |
Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone
CR at EOI was determined by Investigator according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 16.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 29.7 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 28.1 |
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
CR at EOI was assessed by Investigator according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 66.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 60.0 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 33.3 |
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
CR at EOI was determined by IRC according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 16.7 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 31.4 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 12.5 |
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of > 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase > 3 x baseline and an increase in direct bilirubin > 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | 0.0 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | 50.0 |
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | 0.0 |
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 0.0 |
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | 0.0 |
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | 0.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0.0 |
Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans
OR was defined as percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake> mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions;no new lesions & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. Partial response (PR) based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). Percentages have been rounded off up to the second decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 10.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 72.50 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 46.20 |
Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans
OR was defined percentage of participants with CR or PR assessed by the investigator according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes & ELS with score of 1, 2, 3 with or without residual mass on 5PS, where 1=no uptake above background 2=uptake ≤ mediastinum 3=uptake> mediastinum but ≤ liver 4=uptake moderately > liver 5=uptake markedly higher than liver and/or new lesions;no new lesions & no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes & ELS with score of 4 or 5 with reduced uptake compared with baseline & residual masses of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline(diffuse uptake compatible with reactive changes from chemotherapy allowed). Percentages are rounded off. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 10.0 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 80.0 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 46.20 |
Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 12.5 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 91.4 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 53.1 |
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in the sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point. (NCT02600897)
Timeframe: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 100.0 |
| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 11.1 |
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 89.2 |
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 59.4 |
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. (NCT02600897)
Timeframe: Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline prevalence of ADAs | Post baseline incidence of ADAs |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 1 | 0 |
,| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 1 | 0 |
Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab
The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. (NCT02600897)
Timeframe: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline prevalence of ADAs | Post baseline incidence of ADAs |
|---|
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0 | 0 |
,| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | 0 | 0 |
Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab
The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. (NCT02600897)
Timeframe: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline prevalence of ADAs | Post baseline incidence of ADAs |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 0 | 0 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | 0 | 0 |
,| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | 3 | 0 |
Observed Plasma Lenalidomide Concentration
(NCT02600897)
Timeframe: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 2h | Induction Cycle 1 Day 15 / Predose | Induction Cycle 1 Day 15 / 30 min | Induction Cycle 1 Day 15 / 1h | Induction Cycle 1 Day 15 / 2h | Induction Cycle 1 Day 15 / 4h | Induction Cycle 1 Day 15 / 8h | Induction Cycle 6 Day 1 / 2h | Unscheduled / 2h |
|---|
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 306 | 9.99 | 124 | 236 | 305 | 214 | 103 | 237 | 199 |
Observed Plasma Lenalidomide Concentration
(NCT02600897)
Timeframe: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 2h | Induction Cycle 1 Day 15 / Predose | Induction Cycle 1 Day 15 / 30 min | Induction Cycle 1 Day 15 / 1h | Induction Cycle 1 Day 15 / 2h | Induction Cycle 1 Day 15 / 4h | Induction Cycle 1 Day 15 / 8h | Induction Cycle 6 Day 1 / 2h |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | NA | 201 | 8.74 | 179 | 189 | 202 | 116 | 56.8 | 110 |
,| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 305 | 5.20 | 202 | 272 | 200 | 152 | 49.8 | 227 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | NA | 144 | 0.729 | 1.95 | 40.8 | 93.3 | 65.7 | 29.2 | 76.1 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | NA | 25.2 | 5.43 | 12.5 | 69.9 | 118 | 79.9 | 44.0 | 36.2 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | NA | 237 | 2.64 | 41.7 | 224 | 232 | 134 | 57.0 | 258 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 197 | 8.33 | 73.3 | 187 | 328 | 245 | 105 | 255 |
,| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | NA | 118 | 5.97 | 64.0 | 61.4 | 117 | 96.4 | 35.0 | 124 |
,| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 277 | 10.4 | 94.5 | 245 | 242 | 205 | 103 | 153 |
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days (NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | micrograms per milliliter (μg/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Induction Cycle 6 Day 1 / 30 mins | EOI / Predose | Maintenance Month 1 / Predose | Maintenance Month 7 / Predose | Day 120 Post Last Dose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | NA | 394 | 451 | 830 | 354 | 103 | 255 | 730 | 108 | 231 | 128 | 29.1 |
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days (NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | micrograms per milliliter (μg/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Induction Cycle 6 Day 1 / 30 mins | Maintenance Month 7 / Predose | Maintenance Month 13 / Predose | Maintenance Month 19 / Predose | 1 Year Post Last Dose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | NA | 351 | 386 | 695 | 344 | 653 | 327 | 1.18 | 229 | 269 | 204 | 0.377 |
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days (NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | micrograms per milliliter (μg/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Induction Cycle 6 Day 1 / 30 mins | Maintenance Month 1 / Predose | Maintenance Month 7 / Predose | Maintenance Month 13 / Predose | Maintenance Month 19 / Predose | Study Drug Discontinuation |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 333 | 481 | 667 | 405 | 742 | 384 | 751 | 230 | 125 | 134 | 154 | 17.3 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | NA | 358 | 372 | 749 | 321 | 644 | 504 | 804 | 381 | 212 | 142 | 354 | 46.4 |
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days (NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | micrograms per milliliter (μg/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Induction Cycle 6 Day 1 / 30 mins | Maintenance Month 1 / Predose | Maintenance Month 7 / Predose | Maintenance Month 13 / Predose | Maintenance Month 19 / Predose | Study Drug Discontinuation | Day 120 Post Last Dose | 1 Year Post Last Dose | Unscheduled / Predose |
|---|
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 182 | 312 | 588 | 270 | 547 | 255 | 543 | 176 | 135 | 150 | 165 | 87.5 | 44.5 | 0.340 | 561 |
Observed Serum Rituximab Concentration
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Induction Cycle 6 Day 1 / 30 mins |
|---|
| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | NA | 151 | 25.6 | 133 | 20.4 | 159 | 15.3 | 135 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | NA | 203 | 33.3 | 172 | 74.6 | 224 | 79.5 | 250 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 175 | 31.7 | 222 | 53.1 | 220 | 74.7 | 233 |
,| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 174 | 26.4 | 194 | 58.3 | 228 | 68.9 | 256 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Study Drug Discontinuation |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | NA | 580 | 50.2 | 17.3 | 4.96 | 555 | 5.34 | 32.9 | 7.70 | 0.180 |
,| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 432 | 27.7 | 6.73 | 2.50 | 295 | 7.68 | 531 | 9.70 | 0.180 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | NA | 660 | 80.0 | 24.7 | 6.55 | 623 | 11.5 | 416 | 19.9 | 0.635 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Unscheduled / Predose |
|---|
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 522 | 56.6 | 16.9 | 5.32 | 451 | 11.3 | 645 | 11.8 | 9.78 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Study Drug Discontinuation | Unscheduled / Predose |
|---|
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 333 | 11.9 | 5.95 | 1.88 | 481 | 8.99 | 492 | 9.82 | 1.71 | 23.1 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | NA | 476 | 11.4 | 2.50 | 0.961 | 508 | 8.47 | 519 | 9.37 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | NA | 568 | 58.9 | 22.3 | 7.44 | 537 | 4.19 | 371 | 3.06 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | NA | 106 | 52.0 | 18.3 | 5.58 | 568 | 8.25 | 507 | 11.5 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 513 | 43.9 | 18.6 | 6.12 | 716 | 11.7 | 737 | 15.8 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Study Drug Discontinuation |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | NA | 0.228 | 1.15 | 0.457 | 0.0280 | 0.151 | 0.0431 | 0.0817 | 0.0367 | 0.0180 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | NA | 0.160 | 2.05 | 0.459 | 0.0315 | 0.138 | 0.117 | 0.156 | 0.0929 | 0.0180 |
,| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 0.233 | 1.64 | 0.435 | 0.0334 | 0.136 | 0.0283 | 0.0752 | 0.0267 | 0.0180 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Unscheduled / Predose |
|---|
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 0.297 | 2.56 | 0.843 | 0.0713 | 0.210 | 0.0776 | 0.213 | 0.0852 | 0.0180 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose | Study Drug Discontinuation | Unscheduled / Predose |
|---|
| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 0.347 | 1.12 | 0.294 | 0.0268 | 0.102 | 0.0366 | 0.102 | 0.0342 | 0.0180 | 0.180 |
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 1 Day 1 / 30 mins | Induction Cycle 1 Day 8 | Induction Cycle 1 Day 15 | Induction Cycle 2 Day 1 / Predose | Induction Cycle 2 Day 1 / 30 mins | Induction Cycle 4 Day 1 / Predose | Induction Cycle 4 Day 1 / 30 mins | Induction Cycle 6 Day 1 / Predose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | NA | 0.420 | 2.40 | 0.387 | 0.0244 | 0.151 | 0.0672 | 0.104 | 0.0821 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | NA | 0.156 | 1.89 | 0.485 | 0.0501 | 0.186 | 0.0180 | 0.0180 | 0.0180 |
,| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | NA | 0.167 | 1.36 | 0.456 | 0.0310 | 0.123 | 0.0344 | 0.133 | 0.0517 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 0.298 | 3.65 | 0.683 | 0.0527 | 0.157 | 0.0729 | 0.208 | 0.0405 |
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 2 Day 1 / Predose | Induction Cycle 4 Day 1 / Predose | 1 Year Post Last Dose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 15 mg L + 1000 mg G in FL | NA | 0.200 | 2.57 | 0.0250 |
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 2 Day 1 / Predose | Induction Cycle 4 Day 1 / Predose | Study Drug Discontinuation |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 0.622 | 2.12 | 0.0903 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 1000 mg G in FL | NA | 2.01 | 4.45 | 0.170 |
,| Dose-escalation Phase: 1.8 mg Pola + 10 mg L + 375 mg R in DLBCL | NA | 1.57 | 0.900 | 1.50 |
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 2 Day 1 / Predose | Induction Cycle 4 Day 1 / Predose | Study Drug Discontinuation | Day 120 Post Last Dose |
|---|
| Dose-escalation Phase: 1.8 mg Pola + 15 mg L + 375 mg R in DLBCL | NA | 1.61 | 2.96 | 6.16 | 0.208 |
,| Dose-escalation Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 1.47 | 3.10 | 3.25 | 0.107 |
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 2 Day 1 / Predose | Induction Cycle 4 Day 1 / Predose | Study Drug Discontinuation | Day 120 Post Last Dose | 1 Year Post Last Dose |
|---|
| Dose-escalation Phase: 1.4 mg Pola + 10 mg L + 1000 mg G in FL | NA | 1.47 | 1.83 | 0.106 | 0.0661 | 0.0250 |
,| Expansion Phase: 1.4 mg Pola + 20 mg L + 1000 mg G in FL | NA | 0.339 | 2.31 | 0.175 | 0.0365 | 0.0357 |
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
(NCT02600897)
Timeframe: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Induction Cycle 1 Day 1 / Predose | Induction Cycle 2 Day 1 / Predose | Induction Cycle 4 Day 1 / Predose | Study Drug Discontinuation | Day 120 Post Last Dose | 1 Year Post Last Dose | Unscheduled / Predose |
|---|
| Expansion Phase: 1.8 mg Pola + 20 mg L + 375 mg R in DLBCL | NA | 1.35 | 3.42 | 0.455 | 0.0666 | 0.0250 | 2.59 |
Disease Free Survival
(NCT02619682)
Timeframe: Median of 4.6 years from start of study therapy
| Intervention | Participants (Count of Participants) |
|---|
| Post Autologous Transplant Maintenance | 11 |
Number of Participants With Adverse Events, Graded According to CTCAE Version 4.0
Adverse events Toxicity during the 24 months plus one month of post autologous transplant maintenance therapy (NCT02619682)
Timeframe: 2 years plus one month
| Intervention | Participants (Count of Participants) |
|---|
| Post Autologous Transplant Maintenance | 30 |
Overall Survival
all MM patients who got post autologous transplant study therapy (NCT02619682)
Timeframe: Median 4.6 years from start of therapy
| Intervention | Participants (Count of Participants) |
|---|
| Post Autologous Transplant Maintenance | 21 |
Number of Participants With Dose-limiting Toxicities (DLTs) During Cycle 2 of Study Treatment
Does limiting toxicity (DLT) is defined as any one of the following events occurring during Cycle 2 of treatment and assessed by the investigator as related to study treatment: - Adverse event of any grade that leads to a delay of more than 14 days at the start of the next treatment cycle; - Hematologic adverse events (neutropenia, thrombocytopenia); - Non-hematologic adverse event, except IRRs, diarrhea, nausea or vomiting (NCT02631577)
Timeframe: Day 1 - Day 28 of second cycle
| Intervention | Number of Participants (Number) |
|---|
| Atezolizumab-G-lena 15mg | 0 |
| Atezolizumab-G-lena 20mg | 0 |
Serum Concentration of Obinutuzumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | mcg/mL (Mean) |
|---|
| Ind C1 D1 - Predose | Ind C1 D1 - 30 min. Postdose | Ind C2 D1 - Predose | Ind C2 D1 - 30 min. Postdose | Ind C4 D1 - Predose | Ind C4 D1 - 30 min. Postdose | Ind C6 D1 - Predose | Ind C6 D1 - 30 min. Postdose | Maint M1 - Predose | Maint M7 - Predose | Maint M13 - Predose | Maint M19 - Predose | TRTC | OD120FU | O1YFU |
|---|
| Atezolizumab-G-lena 20mg | 0.634 | 375 | 392 | 753 | 301 | 657 | 272 | 652 | 201 | 112 | 104 | 111 | 148 | 46.2 | 57.9 |
Percentage of Participants Achieving CR at EOI, as Determined by the Investigator Using Modified Lugano 2014 Criteria
CR was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the Investigator. (NCT02631577)
Timeframe: 6 months (up to CCOD of 23 October 2018)
| Intervention | Percentage of Participants (Number) |
|---|
| Atezolizumab-G-lena 20mg | 75 |
Number of Participants Positive for Human Anti-human Antibodies (HAHA) to Obinutuzumab
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples from participants were negative for HAHAs to obinutuzumab and the results are shown below. (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Baseline - Negative | Ind C6 D1 - Negative | Study drug completion or early discontinuation - Negative | OB, PK, IMMUNO FU 120D - Negative | OB, PK, IMMUNO FU 1YR - Negative |
|---|
| Atezolizumab-G-lena 15mg | 4 | 3 | 0 | 1 | 2 |
,| Atezolizumab-G-lena 20mg | 34 | 27 | 15 | 11 | 4 |
Percentage of Participants Achieving CR at EOI, as Determined by the IRC and Investigator Using Lugano 2014 Criteria
CR was evaluated through use of CT scans, using the Lugano 2014 criteria. Response was determined by the IRC and by the Investigator. (NCT02631577)
Timeframe: 6 months (up to CCOD of 23 October 2018)
| Intervention | Percentage of Participants (Number) |
|---|
| Determined by the IRC with CT or MRI | Determined by Investigator with CT or MRI |
|---|
| Atezolizumab-G-lena 20mg | 31.3 | 50 |
Percentage of Participants With Adverse Events and Serious Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Adverse Events | Serious Adverse Events |
|---|
| Atezolizumab-G-lena 15mg | 4 | 2 |
,| Atezolizumab-G-lena 20mg | 34 | 16 |
Percentage of Participants With Best Response (CR or PR) During the Study as Determined by the Investigator on the Basis of CT Scans Alone
Best Response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the Investigator. (NCT02631577)
Timeframe: 30 months
| Intervention | Percentage (Number) |
|---|
| Best Response (CR,PR) | CR | PR |
|---|
| Atezolizumab-G-lena 20mg | 87.5 | 68.8 | 18.8 |
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of CT Scans Alone
Objective response was evaluated through use of CT scans alone, using the Lugano 2014. Response was determined by the IRC and by the Investigator. (NCT02631577)
Timeframe: 6 months (up to CCOD of 23 October 2018)
| Intervention | Percentage of Participants (Number) |
|---|
| Determined by IRC, based on Lugano 2014 - CT | Determined by Inv., based on Lugano 2014 - CT |
|---|
| Atezolizumab-G-lena 20mg | 81.3 | 87.5 |
Percentage of Participants With Objective Response (CR or PR) at EOI as Determined by the IRC and Investigator on the Basis of PET-CT Scans
Objective response was evaluated through use of PET-CT scans, using the Lugano 2014 or modified Lugano 2014 criteria. Response was determined by the IRC and by the Investigator. (NCT02631577)
Timeframe: 6 months (up to CCOD of 23 October 2018)
| Intervention | Percentage of Participants (Number) |
|---|
| Determined by IRC, based on Lugano 2014 - PET | Determined by Inv., based on Lugano 2014 - PET | Determined by IRC, Modified Lugano 2014 - PET-CT | Determined by Inv, Modified Lugano 2014 - PET-CT |
|---|
| Atezolizumab-G-lena 20mg | 81.3 | 84.4 | 78.1 | 84.4 |
Number of Participants Positive for Anti-therapeutic Antibodies (ATAs) to Atezolizumab
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year. All baseline and post-baseline samples were negative for ATAs to atezolizumab and the results are shown below. (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Ind C2 D1 - Negative | Ind C2 D15 - Negative | Ind C4 D1 - Negative | Ind C6 D1 - Negative | Maint M1 - Negative | Maint M4 - Negative | Maint M7 - Negative | Maint M13 - Negative | Maint M19 - Negative | Study drug completion or early discontinuation - Negative | ATEZO, PK, IMMUNO FU 120D - Negative | ATEZO, PK, IMMUNO FU 1YR - Negative |
|---|
| Atezolizumab-G-lena 15mg | 4 | 2 | 3 | 3 | 3 | 3 | 2 | 1 | 2 | 2 | 1 | 2 |
,| Atezolizumab-G-lena 20mg | 31 | 32 | 29 | 28 | 27 | 25 | 21 | 20 | 12 | 15 | 11 | 3 |
Serum Concentration of Atezolizumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Ind C2 D1 - Predose | Ind C2 D1 - 30 min. Postdose | Ind C2 D15 - Predose | Ind C4 D1 - Predose | Ind C4 D1 - 30 min. Postdose | Ind C6 D1 - Predose | Maint M1 - Predose | Maint M1 - Day 2, 30 min. Postdose | Maint M4 - Predose | Maint M7 - Predose | Maint M13 - Predose | Maint M19 - Predose | TRTC | PK FU 120D |
|---|
| Atezolizumab-G-lena 20mg | 0.184 | 279 | 90.0 | 226 | 477 | 279 | 172 | 666 | 292 | 322 | 309 | 327 | 116 | 38.4 |
Serum Concentration of Lenalidomide (ng/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; HR = Hour (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | nanograms/milliliter (ng/mL) (Mean) |
|---|
| Ind C1 D15 - Predose | Ind C1 D15 - 2.0 hr. Postdose | Ind C2 D15 - Predose | Ind C2 D15 - 30 min. Postdose | Ind C2 D15 -1.0 hr. Postdose | Ind C2 D15 - 2.0 hr. Postdose | Ind C2 D15 - 4.0 hr. Postdose | Ind C2 D15 - 8.0 hr. Postdose | Ind C6 D15 - Predose | Ind C6 D15 - 2.0 hr. Postdose |
|---|
| Atezolizumab-G-lena 15mg | 12.6 | 254 | 3.57 | 241 | 224 | 146 | 95.8 | 45.9 | 5.72 | 200 |
,| Atezolizumab-G-lena 20mg | 13.0 | 294 | 15.0 | 293 | 354 | 262 | 150 | 68.4 | 9.17 | 214 |
Serum Concentration of Obinutuzumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | mcg/mL (Mean) |
|---|
| Ind C1 D1 - 30 min. Postdose | Ind C2 D1 - Predose | Ind C2 D1 - 30 min. Postdose | Ind C4 D1 - Predose | Ind C4 D1 - 30 min. Postdose | Ind C6 D1 - Predose | Ind C6 D1 - 30 min. Postdose | Maint M1 - Predose | Maint M7 - Predose | Maint M13 - Predose | Maint M19 - Predose | OD120FU | O1YFU |
|---|
| Atezolizumab-G-lena 15mg | 364 | 288 | 606 | 175 | 509 | 230 | 503 | 114 | 66.1 | 77.9 | 94.0 | 23.3 | 46.9 |
Serum Concentration of Atezolizumab (mcg/mL)
The following abbreviations apply in the table: Ind C = Induction Cycle; D = Day; Maint M = Maintenance Month; TRTC = Study Drug Completion or Early Discontinuation; PK FU = Pharmacokinetics and Immunogenicity Follow-up; YR = Year (NCT02631577)
Timeframe: Baseline up to approximately 59 months
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Ind C2 D1 - 30 min. Postdose | Ind C2 D15 - Predose | Ind C4 D1 - Predose | Ind C4 D1 - 30 min. Postdose | Ind C6 D1 - Predose | Maint M1 - Predose | Maint M1 - Day 2, 30 min. Postdose | Maint M4 - Predose | Maint M7 - Predose | Maint M13 - Predose | Maint M19 - Predose | PK FU 120D |
|---|
| Atezolizumab-G-lena 15mg | 345 | 73.8 | 128 | 340 | 194 | 79.0 | 653 | 174 | 209 | 203 | 351 | 46.0 |
Percentage of Participants Achieving Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria
Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC. (NCT02631577)
Timeframe: 6 months (up to clinical cut-off date (CCOD) of 23 October 2018)
| Intervention | Percentage of Participants (Number) |
|---|
| Atezolizumab-G-lena 20mg | 71.9 |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Durvalumab (DURVA) after multiple doses on day 1 obtained from the observed concentration versus time data (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | day (Median) |
|---|
| Cohort A: High Risk, TNE | 0.051 |
| Cohort B: >=65 Years Old, TNE | 0.106 |
| Cohort C: High Risk, Post-transplant | 0.180 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Lenalidomide (LEN) after multiple doses on day 15 obtained from the observed concentration versus time data (NCT02685826)
Timeframe: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour (Median) |
|---|
| Cohort A: High Risk, TNE | 2.000 |
| Cohort B: >=65 Years Old, TNE | 1.000 |
| Cohort C: High Risk, Post-transplant | 1.042 |
Participants With Treatment Emergent Adverse Events (TEAE)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE includes AEs between the first dose date of either study drug and 90 days after the last dose of study drug. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death (NCT02685826)
Timeframe: Day 1 up to Week 84 (the longer of 90 days after discontinuing treatment with DURVA, or 28 days after the last dose of LEN or dex)
| Intervention | Participants (Count of Participants) |
|---|
| >= 1 TEAE | >=1 treatment-related TEAE | >=1 related to DURVA | >=1 related to LEN | >=1 related to dex | >=1 TEAE of severity grade 3 or 4 | >=1 severity 3/4, related to study drug | >=1 severity 3/4, related to DURVA | >=1 severity 3/4, related to LEN | >=1 severity 3/4, related to dex | >=1 Grade 5 TEAE (Death) | >=1 Grade 5 TEAE related to study drug | >=1 Grade 5 TEAE related to DURVA | >=1 Grade 5 TEAE related to LEN | >=1 Grade 5 TEAE related to dex | >=1 Serious TEAE | >=1 Serious TEAE related to study drug | >=1 Serious TEAE related to DURVA | >=1 Serious TEAE related to LEN | >=1 Serious TEAE related to dex | >=1 TEAE leading to discontinuation of study drug | >= TEAE leading to discontinuation of DURVA | >= TEAE leading to discontinuation of LEN | >= TEAE leading to discontinuation of dex | >=1 leading to delay/reduction/interruption drug | >=1 leading to dose delay of DURVA | >=1 leading to infusion interruption of DURVA | >=1 leading to dose reduction of LEN | >=1 leading to interruption of LEN | >=1 leading to dose reduction of dex | >=1 leading to interruption of dex |
|---|
| Cohort A: High Risk, TNE | 24 | 22 | 16 | 22 | 16 | 19 | 13 | 7 | 11 | 5 | 1 | 0 | 0 | 0 | 0 | 12 | 8 | 5 | 6 | 5 | 3 | 2 | 3 | 2 | 14 | 10 | 0 | 2 | 13 | 1 | 9 |
,| Cohort B: >=65 Years Old, TNE | 9 | 8 | 4 | 8 | 6 | 8 | 8 | 4 | 8 | 2 | 0 | 0 | 0 | 0 | 0 | 6 | 4 | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 7 | 3 | 0 | 2 | 5 | 3 | 3 |
,| Cohort C: High Risk, Post-transplant | 18 | 17 | 15 | 15 | NA | 7 | 6 | 4 | 4 | NA | 1 | 1 | 1 | 0 | NA | 4 | 4 | 4 | 2 | NA | 1 | 1 | 0 | NA | 6 | 4 | 1 | 3 | 5 | NA | NA |
Time to Response (for Cohorts A and B)
Time to response (for responders only, per IMWG Uniform Response Criteria) is calculated as the time from the first date of dosing of study medication to the first date of documented response (PR or better). (NCT02685826)
Timeframe: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
| Intervention | weeks (Median) |
|---|
| Cohort A: High Risk, TNE | 4.20 |
| Cohort B: >=65 Years Old, TNE | 4.10 |
Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28)
A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for >= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level <=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption >= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If >=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg (NCT02685826)
Timeframe: First treatment cycle: Day 1 to Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: High Risk, TNE | 1 |
| Cohort B: >=65 Years Old, TNE | 1 |
| Cohort C: High Risk, Post-transplant | 0 |
Participants Who Had Either Disease Progression or Death
This outcome was originally defined as a Kaplan-Meier estimate of progression-free survival (PFS) which estimated the time between first date of dosing of study medication and disease progression, as determined by the investigator using the IMWG Uniform Response Criteria, or death during study treatment, whichever occurred earlier. However due to the early study termination and limited follow-up time, the majority of participants were censored for PFS analysis. Data reported instead represent the number of participants who died during study treatment or had disease progression within 90 days of the last dose of durvalumab. (NCT02685826)
Timeframe: Day 1 up to Week 84
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: High Risk, TNE | 4 |
| Cohort B: >=65 Years Old, TNE | 1 |
| Cohort C: High Risk, Post-transplant | 3 |
Participants Who Died Up To Data Cut-off Date (15 December 2017)
This outcome was originally defined as a Kaplan-Meier estimate of overall survival (OS) and was defined as the time between first date of dosing of study medication and death due to any cause. However due to the early study termination and limited follow-up time, the majority of participants were censored for OS analysis. Data reported instead represent the number of participants who died due to any cause from Day 1 up to data cut-off. (NCT02685826)
Timeframe: Day 1 up to Week 87
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: High Risk, TNE | 2 |
| Cohort B: >=65 Years Old, TNE | 0 |
| Cohort C: High Risk, Post-transplant | 1 |
Participants Who Developed Anti-drug Antibody Against Durvalumab
The number of participants who develop antidrug antibody against durvalumab at any of the sampling timepoints during the study. (NCT02685826)
Timeframe: Pre-dose samples on Day 1 of cycles 1, 2, 4, 6, 10, and 14 (study days 1, 29, 85, 141, 253, 393)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: High Risk, TNE | 0 |
| Cohort B: >=65 Years Old, TNE | 1 |
| Cohort C: High Risk, Post-transplant | 0 |
Lenalidomide (LEN) Plasma PK Parameters in Cycle 1 Day 15: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour*ng/mL (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 1911.739 |
| Cohort B: >=65 Years Old, TNE | 1754.349 |
| Cohort C: High Risk, Post-transplant | 629.151 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 409.764 |
| Cohort B: >=65 Years Old, TNE | 452.850 |
| Cohort C: High Risk, Post-transplant | 171.235 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Lenalidomide (LEN) after multiple doses on day 1 obtained from the observed concentration versus time data (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour (Median) |
|---|
| Cohort A: High Risk, TNE | 1.050 |
| Cohort B: >=65 Years Old, TNE | 1.925 |
| Cohort C: High Risk, Post-transplant | 1.150 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Terminal Elimination Half-life (t1/2)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 3.477 |
| Cohort B: >=65 Years Old, TNE | 3.051 |
| Cohort C: High Risk, Post-transplant | 2.883 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 395.774 |
| Cohort B: >=65 Years Old, TNE | 354.018 |
| Cohort C: High Risk, Post-transplant | 161.372 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour*ng/mL (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 1468.102 |
| Cohort B: >=65 Years Old, TNE | 1442.549 |
| Cohort C: High Risk, Post-transplant | 591.085 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | hour*ng/mL (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 2534.684 |
| Cohort B: >=65 Years Old, TNE | 2011.889 |
| Cohort C: High Risk, Post-transplant | 768.104 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Volume of Distribution (Vz/F)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | liters (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 44.329 |
| Cohort B: >=65 Years Old, TNE | 54.689 |
| Cohort C: High Risk, Post-transplant | 54.157 |
Durvalumab (DURVA) Serum Pharmacokinetic (PK) Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | day*µg/L (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 3535033.014 |
| Cohort B: >=65 Years Old, TNE | 3582905.960 |
| Cohort C: High Risk, Post-transplant | 4026520.655 |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | day*µg/L (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 4944601.671 |
| Cohort B: >=65 Years Old, TNE | 5532568.144 |
| Cohort C: High Risk, Post-transplant | 6531541.670 |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Clearance (CL)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | L/day (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 0.303 |
| Cohort B: >=65 Years Old, TNE | 0.271 |
| Cohort C: High Risk, Post-transplant | 0.230 |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | µg/L (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 449280.231 |
| Cohort B: >=65 Years Old, TNE | 452827.419 |
| Cohort C: High Risk, Post-transplant | 482602.748 |
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Clearance (CL/F)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
| Intervention | L/hour (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 8.838 |
| Cohort B: >=65 Years Old, TNE | 12.426 |
| Cohort C: High Risk, Post-transplant | 13.019 |
Kaplan-Meier Estimates for Duration of Response (for Cohort A and B)
Duration of response (for responders only) was defined as the time from earliest date of documented response (PR or better) to the earliest date of disease progression (DP) as determined by the investigator per IMWG Uniform Response criteria or death during study treatment, whichever occurred first. (NCT02685826)
Timeframe: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
| Intervention | months (Median) |
|---|
| Cohort A: High Risk, TNE | 10.3 |
| Cohort B: >=65 Years Old, TNE | NA |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Volume of Distribution (Vz)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | liters (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 4.244 |
| Cohort B: >=65 Years Old, TNE | 4.582 |
| Cohort C: High Risk, Post-transplant | 4.563 |
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Terminal Elimination Half-life (t1/2)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values. (NCT02685826)
Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
| Intervention | day (Geometric Mean) |
|---|
| Cohort A: High Risk, TNE | 10.984 |
| Cohort B: >=65 Years Old, TNE | 13.376 |
| Cohort C: High Risk, Post-transplant | 15.844 |
Percentage of Participants With Progression-Free Survival in Pairwise Analysis
This is the pairwise comparison for percentage of participants with Progression-Free Survival. Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm. (NCT02728102)
Timeframe: 2 year
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 79.3 |
| Lenalidomide and GM-CSF | 91.3 |
| Maintenance Lenalidomide | 84.9 |
Number of Grade ≥ 3 Toxicities
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. All Grade ≥ 3 toxicities will be tabulated for treatment arms. Toxicities are categorized by organ system according to the CTCAE. Toxicities that involve multiple questions per organ system are combined in one category. (NCT02728102)
Timeframe: 2 years
| Intervention | Toxicities (Number) |
|---|
| Auditory Disorders | Blood and Lymphatic Disorders | Cardiovascular Disorders | GI Disorders | General Disorders | Hepatobiliary/Pancreas Disorders | Immune System Disorders | Investigations | Metabolism and Nutrition Disorders | Musculoskeletal and Connective Tissue Disorders | Nervous System Disorders | Renal Disorders | Respiratory, Thoracic and Mediastinal Disorders | Skin and Subcutaneous Tissue Disorders | Vascular Disorders | Abnormal Liver Symptoms |
|---|
| Lenalidomide and GM-CSF | 0 | 40 | 3 | 4 | 2 | 1 | 0 | 0 | 1 | 1 | 5 | 0 | 1 | 5 | 11 | 1 |
,| Lenalidomide, Vaccine, and GM-CSF | 1 | 81 | 4 | 15 | 5 | 4 | 2 | 2 | 7 | 1 | 14 | 1 | 5 | 4 | 6 | 0 |
,| Maintenance Lenalidomide | 0 | 38 | 2 | 2 | 2 | 1 | 0 | 1 | 3 | 2 | 1 | 2 | 2 | 7 | 3 | 0 |
Percentage of Participants With 1-year Response Rate of CR/sCR
The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. (NCT02728102)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 52.9 |
| Lenalidomide With or Without GM-CSF | 50.0 |
Percentage of Participants With Grade 2 and 3 Infections
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine and the combined non-vaccine groups using the Gray's test. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 26.6 |
| Lenalidomide With or Without GM-CSF | 23.2 |
Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms
The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm and the combined non-vaccine arms using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 20.7 |
| Lenalidomide With or Without GM-CSF | 11.8 |
Participants With Grade ≥ 3 Toxicities
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. The number of participants experiencing Grade ≥ 3 toxicity are displayed for the vaccine and non-vaccine arms separately. The proportion of participants experiencing Grade ≥ 3 toxicity are compared between the vaccine and non-vaccine arms combined. (NCT02728102)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 53 |
| Lenalidomide With or Without GM-CSF | 49 |
Participants Response to Treatment
A participant's disease status is evaluated based on the International Uniform Response Criteria per protocol. Before disease progression (PD), all disease classifications including stringent complete response (sCR), complete response (CR), very good partial remission (VGPR), partial response (PR), stable disease (SD) are relative to participant's disease status at study entry. Disease status is 'Not Evaluable' when disease assessment is not required, or disease status is missing. (NCT02728102)
Timeframe: 6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapy
| Intervention | Participants (Count of Participants) |
|---|
| Disease Status at 6 Months72284442 | Disease Status at 6 Months72284444 | Disease Status at 6 Months72284445 | Disease Status at 12 Months72284444 | Disease Status at 12 Months72284442 | Disease Status at 12 Months72284445 | Disease Status at 24 Months72284442 | Disease Status at 24 Months72284444 | Disease Status at 24 Months72284445 | Disease Status at Cycle 3 (Day 57 Assessment)72284442 | Disease Status at Cycle 3 (Day 57 Assessment)72284445 | Disease Status at Cycle 3 (Day 57 Assessment)72284444 | Disease Status at Cycle 6 (Day 141 Assessment)72284445 | Disease Status at Cycle 6 (Day 141 Assessment)72284444 | Disease Status at Cycle 6 (Day 141 Assessment)72284442 | Disease Status at Cycle 9 (Day 225 Assessment)72284442 | Disease Status at Cycle 9 (Day 225 Assessment)72284445 | Disease Status at Cycle 9 (Day 225 Assessment)72284444 | Disease Status at Cycle 12 (Day 309 Assessment)72284442 | Disease Status at Cycle 12 (Day 309 Assessment)72284444 | Disease Status at Cycle 12 (Day 309 Assessment)72284445 | Disease Status at Cycle 15 (Day 393 Assessment)72284444 | Disease Status at Cycle 15 (Day 393 Assessment)72284442 | Disease Status at Cycle 15 (Day 393 Assessment)72284445 | Disease Status at Cycle 18 (Day 477 Assessment)72284445 | Disease Status at Cycle 18 (Day 477 Assessment)72284442 | Disease Status at Cycle 18 (Day 477 Assessment)72284444 | Disease Status at Cycle 21 (Day 561 Assessment)72284445 | Disease Status at Cycle 21 (Day 561 Assessment)72284444 | Disease Status at Cycle 21 (Day 561 Assessment)72284442 | Disease Status at Cycle 24 (Day 654 Assessment)72284445 | Disease Status at Cycle 24 (Day 654 Assessment)72284444 | Disease Status at Cycle 24 (Day 654 Assessment)72284442 |
|---|
| Stringent Complete Response (sCR) | Complete Response (CR) | Very Good Partial Remission (VGPR) | Stable Disease (SD) | Not Evaluable | Partial Response (PR) | Progression (PD) | Dead |
|---|
| Maintenance Lenalidomide | 8 |
| Lenalidomide and GM-CSF | 12 |
| Lenalidomide, Vaccine, and GM-CSF | 22 |
| Maintenance Lenalidomide | 9 |
| Maintenance Lenalidomide | 3 |
| Maintenance Lenalidomide | 2 |
| Maintenance Lenalidomide | 0 |
| Maintenance Lenalidomide | 1 |
| Maintenance Lenalidomide | 10 |
| Lenalidomide, Vaccine, and GM-CSF | 8 |
| Lenalidomide and GM-CSF | 9 |
| Lenalidomide, Vaccine, and GM-CSF | 19 |
| Lenalidomide and GM-CSF | 5 |
| Maintenance Lenalidomide | 14 |
| Lenalidomide, Vaccine, and GM-CSF | 35 |
| Lenalidomide and GM-CSF | 15 |
| Lenalidomide, Vaccine, and GM-CSF | 5 |
| Lenalidomide and GM-CSF | 6 |
| Lenalidomide, Vaccine, and GM-CSF | 13 |
| Lenalidomide, Vaccine, and GM-CSF | 18 |
| Lenalidomide, Vaccine, and GM-CSF | 28 |
| Lenalidomide and GM-CSF | 14 |
| Lenalidomide, Vaccine, and GM-CSF | 1 |
| Lenalidomide, Vaccine, and GM-CSF | 16 |
| Lenalidomide and GM-CSF | 8 |
| Lenalidomide, Vaccine, and GM-CSF | 17 |
| Lenalidomide and GM-CSF | 7 |
| Maintenance Lenalidomide | 15 |
| Lenalidomide, Vaccine, and GM-CSF | 24 |
| Lenalidomide and GM-CSF | 13 |
| Lenalidomide, Vaccine, and GM-CSF | 6 |
| Lenalidomide and GM-CSF | 0 |
| Lenalidomide, Vaccine, and GM-CSF | 2 |
| Lenalidomide and GM-CSF | 2 |
| Lenalidomide, Vaccine, and GM-CSF | 7 |
| Lenalidomide and GM-CSF | 11 |
| Lenalidomide, Vaccine, and GM-CSF | 4 |
| Lenalidomide, Vaccine, and GM-CSF | 3 |
| Lenalidomide, Vaccine, and GM-CSF | 0 |
| Maintenance Lenalidomide | 4 |
| Maintenance Lenalidomide | 13 |
| Lenalidomide, Vaccine, and GM-CSF | 9 |
| Maintenance Lenalidomide | 7 |
| Lenalidomide, Vaccine, and GM-CSF | 20 |
| Maintenance Lenalidomide | 11 |
| Lenalidomide and GM-CSF | 17 |
| Maintenance Lenalidomide | 6 |
| Lenalidomide, Vaccine, and GM-CSF | 11 |
| Lenalidomide, Vaccine, and GM-CSF | 15 |
| Lenalidomide, Vaccine, and GM-CSF | 14 |
| Lenalidomide and GM-CSF | 16 |
| Lenalidomide and GM-CSF | 3 |
| Lenalidomide and GM-CSF | 1 |
| Lenalidomide, Vaccine, and GM-CSF | 12 |
| Lenalidomide and GM-CSF | 4 |
Number of Participants With Minimal Residual Disease (MRD)
Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. Multichannel flow cytometry will be used to establish MRD based on the presence of malignant plasma cells that are CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The number of patients with MRD negative (MRD-) are described using frequencies at pre-randomization and 9th cycle post-randomization and compared between the vaccine arm with the no-vaccine arms combined. (NCT02728102)
Timeframe: Pre-randomization, Post-randomization at Cycle 9
| Intervention | Participants (Count of Participants) |
|---|
| Pre-randomization | Post-randomization at Cycle 9 |
|---|
| Lenalidomide With or Without GM-CSF | 31 | 41 |
,| Lenalidomide, Vaccine, and GM-CSF | 35 | 38 |
Number of Grade 2 and 3 Infections
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after randomization will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient. (NCT02728102)
Timeframe: 2years
| Intervention | infections (Number) |
|---|
| Bacterial | Viral | Fungal | Other |
|---|
| Lenalidomide and GM-CSF | 3 | 6 | 0 | 0 |
,| Lenalidomide, Vaccine, and GM-CSF | 10 | 14 | 0 | 1 |
,| Maintenance Lenalidomide | 6 | 14 | 0 | 1 |
Percentage of Participants With Progression-Free Survival
Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine and the combined non-vaccine arms using the log-rank test. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 79.3 |
| Lenalidomide With or Without GM-CSF | 88.2 |
Percentage of Participants With Overall Survival in Pairwise Analysis
This is the pairwise comparison for percentage of participants with Overall Survival. Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm from time of randomization. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 97 |
| Lenalidomide and GM-CSF | 100 |
| Maintenance Lenalidomide | 96.9 |
Percentage of Participants With Overall Survival
Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine and the combined non-vaccine arms from time of randomization. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 97 |
| Lenalidomide With or Without GM-CSF | 98.5 |
Percentage of Participants With Myeloma Progression in Pairwise Analysis
This is the pairwise comparison for percentage of participants with Myeloma Progression. The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 20.7 |
| Lenalidomide and GM-CSF | 8.7 |
| Maintenance Lenalidomide | 15.1 |
Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis
This is the pairwise comparison for percentage of participants with Grade 2 and 3 infections. Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using the Gray's test. (NCT02728102)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Lenalidomide, Vaccine, and GM-CSF | 26.6 |
| Lenalidomide and GM-CSF | 14.2 |
| Maintenance Lenalidomide | 32.6 |
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose
| Intervention | h*ng/mL (Geometric Least Squares Mean) |
|---|
| Arm B: Ibrutinib 420 mg | 586.396 |
| Arm B: Ibrutinib 560 mg | 436.855 |
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | days*μg/L (Geometric Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 4867431.378 |
| Arm B: Durvalumab + Ibrutinib | 5818262.846 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 4762968.345 |
| Arm D: Durvalumab Monotherapy | 5593532.553 |
Time to First Response
Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants). (NCT02733042)
Timeframe: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
| Intervention | weeks (Median) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 70.85 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 12.60 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 18.20 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 11.85 |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 13.40 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 13.00 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 13.10 |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | 12.10 |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | 12.10 |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 12.35 |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 12.00 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 12.10 |
| Part 2, Arm D HL: DUR 1500 mg | 13.10 |
Time to Maximum Plasma Concentration (Tmax) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | days (Median) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 0.0510 |
| Arm B: Durvalumab + Ibrutinib | 0.0479 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 0.0510 |
| Arm D: Durvalumab Monotherapy | 0.0420 |
Volume of Distribution (Vz) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | liters (Geometric Least Squares Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 5.155 |
| Arm B: Durvalumab + Ibrutinib | 6.451 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 7.418 |
| Arm D: Durvalumab Monotherapy | 5.957 |
Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
| Intervention | hours (Median) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Arm A: Lenalidomide 10 mg | 1.9500 | 3.0333 |
,| Arm A: Lenalidomide 20 mg | 1.1667 | 1.000 |
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
| Intervention | ng/mL (Geometric Least Squares Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Arm B: Ibrutinib 420 mg | 129.704 | 86.840 |
,| Arm B: Ibrutinib 560 mg | 67.728 | 72.436 |
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | days*μg/L (Geometric Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 3120149.759 |
| Arm B: Durvalumab + Ibrutinib | 3225869.344 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 2670168.397 |
| Arm D: Durvalumab Monotherapy | 3053060.746 |
Kaplan-Meier Estimate of Progression-free Survival (PFS)
Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free. (NCT02733042)
Timeframe: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
| Intervention | months (Median) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 8.41 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | NA |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | NA |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | NA |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 28.71 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 9.69 |
| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | 1.25 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 3.82 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 2.48 |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | NA |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | NA |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 14.65 |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 2.06 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | NA |
| Part 2, Arm D FL: DUR 1500 mg | 1.68 |
| Part 2, Arm D DLBCL: DUR 1500 mg | 1.17 |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | 2.76 |
| Part 2, Arm D MCL: DUR 1500 mg | 2.33 |
| Part 2, Arm D HL: DUR 1500 mg | 2.66 |
Maximum Observed Plasma Concentration (Cmax) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | μg/L (Geometric Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 420264.066 |
| Arm B: Durvalumab + Ibrutinib | 361906.229 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 331572.478 |
| Arm D: Durvalumab Monotherapy | 392663.668 |
Kaplan-Meier Estimate of Duration of Response
Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free. (NCT02733042)
Timeframe: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
| Intervention | weeks (Median) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 10.14 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | NA |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | NA |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | NA |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | NA |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 29.29 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | NA |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | NA |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | NA |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | NA |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 24.14 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | NA |
| Part 2, Arm D HL: DUR 1500 mg | 11.14 |
Maximum Observed Plasma Concentration (Cmax) of Lenalidomide
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
| Intervention | ng/mL (Geometric Least Squares Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Arm A: Lenalidomide 10 mg | 141.881 | 107.635 |
,| Arm A: Lenalidomide 20 mg | 309.917 | 174.090 |
Clearance (CL) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | L/day (Geometric Least Squares Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 0.3082 |
| Arm B: Durvalumab + Ibrutinib | 0.2578 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 0.3149 |
| Arm D: Durvalumab Monotherapy | 0.2682 |
Number of Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5). (NCT02733042)
Timeframe: From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | TEAE Related to Any Study Drug | CTCAE Grade 3-4 TEAE | CTCAE Grade 3-4 TEAE Related to Any Study Drug | CTCAE Grade 5 TEAE | CTCAE Grade 5 TEAE Related to Any Study Drug | Serious TEAE | Serious TEAE Related to Any Study Drug | TEAE Leading to Discontinuation of Any Study Drug | TEAE Leading to Dose Modifications of Study Drug |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 8 | 8 | 7 | 7 | 0 | 0 | 4 | 3 | 3 | 3 |
,| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 3 | 3 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 |
,| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 3 | 3 | 3 | 3 | 0 | 0 | 2 | 2 | 0 | 3 |
,| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 3 | 3 | 2 | 1 | 0 | 0 | 2 | 1 | 1 | 3 |
,| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 4 | 4 | 3 | 1 | 0 | 0 | 2 | 0 | 0 | 4 |
,| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 3 | 3 | 2 | 2 | 0 | 0 | 2 | 1 | 0 | 3 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 4 | 4 | 3 | 2 | 0 | 0 | 1 | 0 | 0 | 4 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 5 | 5 | 4 | 2 | 0 | 0 | 3 | 1 | 0 | 4 |
,| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 9 | 9 | 9 | 7 | 0 | 0 | 5 | 3 | 1 | 4 |
,| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | 10 | 10 | 8 | 7 | 0 | 0 | 6 | 2 | 0 | 8 |
,| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | 10 | 9 | 10 | 6 | 1 | 1 | 7 | 3 | 2 | 9 |
,| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 5 | 5 | 5 | 3 | 1 | 0 | 2 | 1 | 2 | 3 |
,| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 10 | 10 | 6 | 5 | 0 | 0 | 5 | 3 | 2 | 7 |
,| Part 2, Arm D CLL/SLL: DUR 1500 mg | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 2, Arm D DLBCL: DUR 1500 mg | 9 | 3 | 7 | 2 | 4 | 0 | 7 | 1 | 0 | 0 |
,| Part 2, Arm D FL: DUR 1500 mg | 5 | 4 | 4 | 3 | 1 | 0 | 4 | 3 | 1 | 2 |
,| Part 2, Arm D HL: DUR 1500 mg | 5 | 2 | 3 | 1 | 0 | 0 | 2 | 0 | 0 | 3 |
,| Part 2, Arm D MCL: DUR 1500 mg | 5 | 3 | 4 | 1 | 0 | 0 | 3 | 0 | 1 | 3 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) - Extended Collection
TEAEs defined as AEs occurring or worsening on or after first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. Intensity of AEs graded according to the NCI CTCAE V. 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5). This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date (assessments made until August 21, 2022). (NCT02733042)
Timeframe: From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the study completion date of August 21, 2022 (up to approximately 75 months).
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | TEAE Related to Any Study Drug | CTCAE Grade 3-4 TEAE | CTCAE Grade 3-4 TEAE Related to Any Study Drug | CTCAE Grade 5 TEAE | CTCAE Grade 5 TEAE Related to Any Study Drug | Serious TEAE | Serious TEAE Related to Any Study Drug | TEAE Leading to Discontinuation of Any Study Drug | TEAE Leading to Dose Modifications of Study Drug |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 8 | 8 | 7 | 7 | 0 | 0 | 4 | 3 | 3 | 5 |
,| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 3 | 3 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 |
,| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 3 | 3 | 3 | 3 | 0 | 0 | 2 | 2 | 0 | 3 |
,| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 3 | 3 | 2 | 1 | 0 | 0 | 2 | 1 | 1 | 3 |
,| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 4 | 4 | 4 | 1 | 0 | 0 | 3 | 0 | 0 | 4 |
,| Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m² | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 3 | 3 | 2 | 2 | 0 | 0 | 2 | 1 | 0 | 3 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 4 | 4 | 3 | 2 | 0 | 0 | 1 | 0 | 0 | 4 |
,| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 5 | 5 | 4 | 2 | 0 | 0 | 3 | 1 | 0 | 4 |
,| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 9 | 9 | 9 | 7 | 0 | 0 | 5 | 3 | 1 | 4 |
,| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | 10 | 10 | 9 | 8 | 0 | 0 | 6 | 3 | 0 | 9 |
,| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | 10 | 9 | 10 | 6 | 1 | 1 | 7 | 3 | 2 | 9 |
,| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 5 | 5 | 5 | 3 | 1 | 0 | 2 | 1 | 2 | 3 |
,| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 10 | 10 | 6 | 5 | 0 | 0 | 5 | 3 | 2 | 7 |
,| Part 2, Arm D CLL/SLL: DUR 1500 mg | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 2, Arm D DLBCL: DUR 1500 mg | 9 | 3 | 7 | 2 | 4 | 0 | 7 | 1 | 0 | 0 |
,| Part 2, Arm D FL: DUR 1500 mg | 5 | 4 | 4 | 3 | 1 | 0 | 4 | 3 | 1 | 2 |
,| Part 2, Arm D HL: DUR 1500 mg | 5 | 2 | 3 | 1 | 0 | 0 | 2 | 0 | 0 | 3 |
,| Part 2, Arm D MCL: DUR 1500 mg | 5 | 3 | 4 | 1 | 0 | 0 | 3 | 0 | 1 | 3 |
Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.
| Intervention | hours (Median) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Arm B: Ibrutinib 420 mg | 2.000 | 1.8833 |
,| Arm B: Ibrutinib 560 mg | 1.9333 | 2.000 |
Terminal Elimination Phase Half-Life (t½) of Durvalumab
(NCT02733042)
Timeframe: Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.
| Intervention | days (Geometric Least Squares Mean) |
|---|
| Arm A: Durvalumab + Lenalidomide ± Rituximab | 11.596 |
| Arm B: Durvalumab + Ibrutinib | 17.344 |
| Arm C: Durvalumab + Bendamustine ± Rituximab | 16.327 |
| Arm D: Durvalumab Monotherapy | 15.399 |
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide
(NCT02733042)
Timeframe: Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose
| Intervention | h*ng/mL (Geometric Least Squares Mean) |
|---|
| Arm A: Lenalidomide 10 mg | 789.297 |
| Arm A: Lenalidomide 20 mg | 805.299 |
Overall Response Rate (ORR) During Durvalumab Treatment
For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL). (NCT02733042)
Timeframe: Up to 13 cycles (12 months)
| Intervention | percentage of participants (Number) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 33.3 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 66.7 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 80.0 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 66.7 |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 75.0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 33.3 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 50.0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 0 |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | 88.9 |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | 60.0 |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 88.9 |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 30.0 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 50.0 |
| Part 2, Arm D FL: DUR 1500 mg | 0 |
| Part 2, Arm D DLBCL: DUR 1500 mg | 0 |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | 0 |
| Part 2, Arm D MCL: DUR 1500 mg | 0 |
| Part 2, Arm D HL: DUR 1500 mg | 20.0 |
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event. (NCT02733042)
Timeframe: Cycle 1 (28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 0 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 3 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 1 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 0 |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 1 |
Overall Response Rate During the Entire Study
For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL). (NCT02733042)
Timeframe: From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
| Intervention | percentage of participants (Number) |
|---|
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg | 66.7 |
| Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | 66.7 |
| Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | 80.0 |
| Part 1, Arm B: DUR 1500 mg + IBR 420 mg | 66.7 |
| Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 75.0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² | 33.3 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 50.0 |
| Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m² | 0 |
| Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | 100.0 |
| Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | 70.0 |
| Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 88.9 |
| Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 30.0 |
| Part 2, Arm C CLL/SLL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | 50.0 |
| Part 2, Arm D FL: DUR 1500 mg | 0 |
| Part 2, Arm D DLBCL: DUR 1500 mg | 0 |
| Part 2, Arm D CLL/SLL: DUR 1500 mg | 0 |
| Part 2, Arm D MCL: DUR 1500 mg | 0 |
| Part 2, Arm D HL: DUR 1500 mg | 20.0 |
Maintenance Feasibility Rate (MFR)
defined as the percentage of patients starting induction treatment with ERd successfully completing treatment to end of maintenance (NCT02843074)
Timeframe: approximately 159 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment, 104 weeks/2 years of maintenance treatment)
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 19 |
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety
Safety data and abnormal lab values and abnormal vital signs were collected and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4.03). (NCT02843074)
Timeframe: weekly for 8 weeks, then every 2 weeks till the start of mobilization for Induction and 70-120 days post-ASCT, every 2 weeks during 16 weeks of Consolidation, and monthly for 24 months of Maintenance, up to 30 days after last dose of study drugs.
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 52 |
Complete Response Rate (CRR) for Complete Time on Study
Defined as the percentage of patients who achieve a complete response (CR) or near complete response (nCR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per International Myeloma Working Group (IMWG) and European Group for Blood and Marrow Transplantation (EBMT) criteria.CR=bone marrow contains ≤5% plasma cells; negative immunofixation on serum and urine; disappearance of soft tissue plasmacytomas. nCR = the absence of myeloma protein on electrophoresis, with positive immunofixation, stable bone disease, and a normal serum calcium concentration. Patient must have completed at least 1 cycle to be included in analysis. (NCT02843074)
Timeframe: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 25 |
Overall Survival (OS)
Defined as the time from start of induction treatment to 3 years post first study treatment or death from any cause, whichever comes first. Patient must have completed at least 1 cycle to be included in analysis. (NCT02843074)
Timeframe: every 4 weeks until end of treatment visit, and up to 3 years thereafter
| Intervention | months (Median) |
|---|
| ERd Therapy | NA |
Progression-free Survival (PFS)
The time from start of induction treatment to documented progressive disease (PD) or death from any cause up to 3 years post first study treatment. PD is defined as an increase of ≥ 25% from the nadir in at least one of the following criteria: serum M-protein (absolute increase must be ≥0.5 g/dL); urine M-protein (absolute increase must be ≥200 mg/24h) ; only in patients with non-measurable serum and urine M-protein levels: difference in involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); only in patients with non-measurable serum and urine M-protein levels and non-measurable disease by FLC levels, bone marrow plasma cell % (absolute % must be ≥10%) OR Definite development of new bone lesions or soft tissue plasmacytomas OR definite increase in the size of existing bone lesions or soft tissue plasmacytomas OR Development of hypercalcemia (corrected serum Ca >11.5mg/dL) for patients without hypercalcemia at baseline. Must have completed 1 cycle to be included. (NCT02843074)
Timeframe: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
| Intervention | months (Median) |
|---|
| ERd Therapy | 29.7002 |
Consolidation Feasibility Rate (CFR)
defined as the percentage of patients starting induction treatment with ERd successfully completing treatment to end of consolidation (NCT02843074)
Timeframe: approximately 55 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment).
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 34 |
Induction Feasibility Rate (IFR)
Defined as the percentage of patients who successfully complete four 28-day cycles of induction therapy with elotuzumab, lenalidomide and dexamethasone (ERd) and start autologous stem cell transplantation (ASCT). (NCT02843074)
Timeframe: approximately 22 weeks (16 weeks of treatment and 6 weeks allowance for planning and scheduling mobilization and ASCT).
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 33 |
Overall Response Rate (ORR) for Complete Time on Study
Defined as percentage of patients receiving at least 1 cycle with confirmed complete response, very good partial response, or partial response (CR, VGPR, or PR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per IMWG and EBMT criteria. CR=bone marrow contains ≤5% plasma cells; negative fixation on serum and urine; the disappearance of soft tissue plasmacytomas. VGPR=serum and urine M-protein detectable by immunofixation but not by electrophoresis or ≥90% reduction from baseline serum and urine M-protein level <100mg for 24h and In case of presence of soft tissue plasmacytoma(s) at baseline, the disappearance of any soft tissue plasmacytomas. PR=≥50% reduction from baseline in serum M-protein and ≥90% reduction from baseline in 24h urinary M-protein or urine M-protein <200 mg/24 hours and In case of presence of soft tissue plasmacytoma(s) at baseline, a reduction in the sum of products of the two longest perpendicular diameters (SPD) by >50%. (NCT02843074)
Timeframe: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| ERd Therapy | 47 |
Percentage of Participants With Overall Stringent Complete Response (sCR)
Overall sCR rate is defined as the percentage of participants who achieved sCR, according to the IMWG criteria. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5 % PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. (NCT02874742)
Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)
| Intervention | Percentage of participants (Number) |
|---|
| At the end of induction prior to ASCT | At the end of ASCT prior to consolidation | At the end of post-ASCT consolidation | At the end of Maintenance Treatment (up to 24 Months) |
|---|
| Randomized: Daratumumab+RVd (D-RVd) | 12.1 | 21.2 | 42.4 | 67.0 |
,| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 7.2 | 14.4 | 32.0 | 48.0 |
,| Safety Run-in: D-RVd | 0 | 43.8 | 56.3 | 93.8 |
Percentage of Participants With Overall Response Rate (ORR)
ORR- percentage of participants who achieved partial response (PR) or better (PR, Very Good Partial Response [VGPR], CR or sCR) based on computerized algorithm as per IMWG criteria. PR -greater than or equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg//24 hours. If serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required. A >=50% reduction in the size of soft tissue plasmacytomas is also required; VGPR-serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours; CR-negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR- in addition to CR a normal FLC ratio, and absence of clonal PCs by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. (NCT02874742)
Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance treatment of 24 months (overall duration up to 34 months)
| Intervention | Percentage of participants (Number) |
|---|
| At the end of induction prior to ASCT | At the end of ASCT prior to consolidation | At the end of post-ASCT consolidation | At the End of Maintenance Treatment (up to 24 Months) |
|---|
| Randomized: Daratumumab+RVd (D-RVd) | 98.0 | 99.0 | 99.0 | 99.0 |
,| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 91.8 | 91.8 | 91.8 | 91.8 |
,| Safety Run-in: D-RVd | 100 | 100 | 100 | 100.0 |
Duration of Complete Response or Better
Duration of CR or better is the duration from the date of initial documentation of a CR or sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease (PR), or relapse from CR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be greater than or equal to [>=] 0.5 gram per deciliter [g/dL] and >=200 milligrams [mg]/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to plasma cells (PCs) proliferative disorder. (NCT02874742)
Timeframe: From randomization to the date of first documented evidence of progressive disease or relapse from CR (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Duration of Response
Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. (NCT02874742)
Timeframe: From the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Duration of Stringent Complete Response (sCR)
Duration of sCR is the duration from the date of initial documentation of a sCR response, according to the IMWG criteria, to the date of first documented evidence of progressive disease, or relapse from sCR. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. (NCT02874742)
Timeframe: From randomization to the date of first documented evidence of progressive disease or relapse from sCR (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Overall Survival (OS)
OS is measured from the date of randomization to the date of the participant's death. (NCT02874742)
Timeframe: From randomization to the date of initial documentation of participant's death (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Percentage of Participants With Stringent Complete Response (sCR)
Percentage of participants who had achieved sCR as determined by the validated computer algorithm according to the International Myeloma Working Group (IMWG) criteria, by the end of post-autologous stem cell transplantation (post-ASCT) consolidation treatment were reported. Complete response (CR) is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. (NCT02874742)
Timeframe: From randomization to post-ASCT consolidation (after Cycle 6) before maintenance treatment (up to 10 months)
| Intervention | Percentage of participants (Number) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 32.0 |
| Randomized: Daratumumab+RVd (D-RVd) | 42.4 |
Progression-free Survival (PFS)
PFS is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease or death, whichever comes first. PD is defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. (NCT02874742)
Timeframe: From randomization to the date of first documented evidence of progressive disease or death (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Time to Complete Response or Better
Time to CR or better is the duration from the date of randomization to the date of initial documentation of CR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. (NCT02874742)
Timeframe: From randomization to the date of initial documentation of CR (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 9.6 |
| Randomized: Daratumumab+RVd (D-RVd) | 8.9 |
| Safety Run-in: D-RVd | 7.7 |
Time to Partial Response (PR) or Better
Time to PR or better is the duration from the date of randomization to the date of initial documentation of PR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. (NCT02874742)
Timeframe: From randomization to the date of initial documentation of PR or better (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 0.8 |
| Randomized: Daratumumab+RVd (D-RVd) | 0.8 |
| Safety Run-in: D-RVd | 0.8 |
Time to Progression (TTP)
TTP is defined as the duration from the date of randomization to the date of first documented evidence of progressive disease according to the IMWG criteria. (NCT02874742)
Timeframe: From randomization to the date of first documented evidence of progressive disease (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | NA |
| Randomized: Daratumumab+RVd (D-RVd) | NA |
| Safety Run-in: D-RVd | NA |
Time to Stringent Complete Response (sCR)
Time to sCR is the duration from the date of randomization to the date of initial documentation of sCR, which was confirmed by a repeated measurement as required by the IMWG criteria. (NCT02874742)
Timeframe: From randomization to the date of initial documentation of sCR (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 14.3 |
| Randomized: Daratumumab+RVd (D-RVd) | 10.2 |
| Safety Run-in: D-RVd | 8.4 |
Time to Very Good Partial Response (VGPR) or Better
Time to VGPR or better is the duration from the date of randomization to the date of initial documentation of VGPR or better, which was confirmed by a repeated measurement as required by the IMWG criteria. (NCT02874742)
Timeframe: From randomization to the date of initial documentation of VGPR or better (up to 5 years)
| Intervention | Months (Median) |
|---|
| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 3.0 |
| Randomized: Daratumumab+RVd (D-RVd) | 2.2 |
| Safety Run-in: D-RVd | 2.1 |
Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better
VGPR or better rate is defined as the percentage of participants who achieved VGPR or better, according to the IMWG criteria. VGPR is defined as serum and urine M-component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. (NCT02874742)
Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)
| Intervention | Percentage of participants (Number) |
|---|
| At the end of induction prior to ASCT | At the end of ASCT prior to consolidation | At the end of post-ASCT consolidation | At the End of Maintenance Period (up to 24 Months) |
|---|
| Randomized: Daratumumab+RVd (D-RVd) | 71.7 | 86.9 | 90.9 | 96.0 |
,| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 56.7 | 66.0 | 73.2 | 77.6 |
,| Safety Run-in: D-RVd | 68.8 | 100 | 100 | 100.0 |
Percentage of Participants With Complete Response (CR) or Better
CR or better rate is defined as the percentage of participants who achieve CR or sCR, according to the IMWG criteria. CR is negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% PCs in bone marrow. sCR is defined as in addition to CR a normal FLC ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry or immunofluorescence or 2 to 4-color flow cytometry. For 2 participants (1 in each randomized treatment group), data were updated by the study sites which resulted in their inclusion to the response-evaluable analysis set after the primary analysis. (NCT02874742)
Timeframe: From randomization to end of following: induction treatment, ASCT, post-ASCT consolidation (after Cycle 6) and at the end of maintenance period of 24 months (overall duration up to 34 months)
| Intervention | Percentage of participants (Number) |
|---|
| At the end of induction prior to ASCT | At the end of ASCT prior to consolidation | At the end of post-ASCT consolidation | At the end of maintenance period (up to 24 Months) |
|---|
| Randomized: Daratumumab+RVd (D-RVd) | 19.2 | 27.3 | 51.5 | 83.0 |
,| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 13.4 | 19.6 | 42.3 | 60.2 |
,| Safety Run-in: D-RVd | 12.5 | 56.3 | 68.8 | 93.8 |
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Minimal residual disease negative rate is defined as the percentage of participants who achieve MRD negative status by the respective time point. Minimal residual disease was evaluated in participants who achieved CR or sCR (including participants with VGPR or better and suspected daratumumab interference) using next-generation sequencing which utilizes multiple myeloma cell DNA from bone marrow aspirates at a threshold of less than (<) 10^5. (NCT02874742)
Timeframe: From randomization to end of following: induction treatment, post-ASCT consolidation (after Cycle 6) (up to 4.5 months), and at the end of maintenance period of 24 months (overall duration up to 34 months)
| Intervention | Percentage of participants (Number) |
|---|
| MRD from randomization to prior to ASCT (10^5) | Post ASCT consolidation (10^5) | At the End of Maintenance Period (up to 24 Months) (10^5) |
|---|
| Randomized: Daratumumab+RVd (D-RVd) | 22.1 | 50.0 | 64.4 |
,| Randomized: Lenalidomide+Bortezomib+Dexamethasone (RVd) | 7.8 | 20.4 | 30.1 |
,| Safety Run-in: D-RVd | 18.8 | 50.0 | 81.3 |
Progression-free Survival
Progression-free survival is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. Patients who receive subsequent treatment for myeloma before disease progression will be censored on the date of their last disease assessment prior to initiation of the subsequent treatment. Transplant will not be considered subsequent treatment. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT02880228)
Timeframe: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 3 years
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) | NA |
Proportion of Complete Response Plus Very Good Partial Response (VGPR)
"The International Myeloma Working Group response criteria was used to assess response to therapy. The proportion of VGPR response at any time during treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients achieving a VGPR, CR, or sCR at any time divided by the total number of evaluable patients. A very good partial response (VGPR) is defined as as a demonstration of:~Serum and urine M-component detectable by immunofixation but not on electrophoresis c or~greater than 90% reduction in serum m-component and urine m-component <100 mg/24 h~If the only measurable disease is FLC, a ≥90% reduction in the difference between involved and involved FLC levels~The proportion of successes will be estimated by the number of patients demonstrating a VGPR or better divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner." (NCT02880228)
Timeframe: Up to 112 days
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) | 0 |
Proportion of Successful Stem Cell Collection
The proportion of successful stem cell collection following initial therapy with the combination of pembrolizumab, lenalidomide and dexamethasone in patients with newly diagnosed MM will be estimated by the number of patients with a successful stem cell collection divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true successful proportion will be calculated. (NCT02880228)
Timeframe: Up to 112 days
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) | 0.4 |
Survival Time
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT02880228)
Timeframe: From time of registration to death due to any cause, assessed up to 3 years
| Intervention | months (Median) |
|---|
| Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) | NA |
Partial Response (PR)
"The PR response after 4 cycles of induction treatment with pembrolizumab added to lenalidomide and dexamethasone will be estimated by the number of patients who achieve a PR, VGPR, CR, or sCR after 4 cycles divided by the total number of evaluable patients. A PR is defined by the following criteria:>~If present at baseline, ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein or to <200 mg/24hrs>~If the only measurable disease is FLC, a ≥50% reduction in the difference between involved and involved FLC levels>~If the only measurable disease is BM, a ≥50% reduction in BM PC's (provided the baseline PC's was ≥30%)>~If present at baseline, ≥50% reduction in the size of soft tissue plasmacytomas>~Exact binomial 95% confidence intervals for the true success rate will be calculated." (NCT02880228)
Timeframe: Up to 112 days
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Lenalidomide, Dexamethasone, Pembrolizumab) | 0 |
Duration of Response
"Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).~The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented." (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | months (Median) |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 2.7 |
| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 8.9 |
| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 5.5 |
| Expansion Cohort I: Follicular Lymphoma at MTD | 8.7 |
Maximum Tolerated Dose (MTD) of Oral Ixazomib
"To determine the MTD of the combination of oral ixazomib and lenalidomide plus rituximab in patients with previously untreated low-grade B cell lymphoma having high tumor burden by GELF criteria or FLIPI 3-5.~MTD will be determined using the first 12 participants 15 months after beginning treatment" (NCT02898259)
Timeframe: 15 months after beginning treatment
| Intervention | mg (Number) |
|---|
| Lenalidomide + Ixazomib + Rituximab | 4 |
Overall Survival
Overall survival is defined as the date of study entry to the date of death. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | Participants (Count of Participants) |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 3 |
| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 3 |
| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 6 |
| Expansion Cohort I: Follicular Lymphoma at MTD | 5 |
| Expansion Cohort 2: Non-Follicular Lymphoma at MTD | 0 |
Progression Free Survival
"A number of participants who survived without disease progression~PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions." (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | Participants (Count of Participants) |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 3 |
| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 2 |
| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 5 |
| Expansion Cohort I: Follicular Lymphoma at MTD | 5 |
| Expansion Cohort 2: Non-Follicular Lymphoma at MTD | 0 |
Time to Progression
Duration of time from start of treatment to time of progression. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | months (Median) |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 0 |
| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 2.5 |
| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 9.0 |
| Expansion Cohort I: Follicular Lymphoma at MTD | 4.6 |
Time to Treatment Failure
Time to treatment failure (event-free survival) is defined as the time from study entry to first event of disease progression, discontinuation of treatment for any reason, initiation of new treatment, or death. (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | months (Median) |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 10 |
| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 0 |
| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 6.1 |
| Expansion Cohort I: Follicular Lymphoma at MTD | 5.8 |
Overall Response Rate
These criteria are based on the Revised Response Criteria for Malignant Lymphoma and include the following categories: Complete Response (CR)(Complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy), Partial Response (PR) (A ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses), Stable Disease (SD) (Failing to attain the criteria needed for a PR or CR, but not fulfilling those for progressive disease), Relapse and Progression (PD) (For determination of relapsed and progressive disease, lymph nodes should be considered abnormal if the long axis is more than 1.5 cm, regardless of the short axis). (NCT02898259)
Timeframe: Up to 15 months after beginning treatment
| Intervention | Participants (Count of Participants) |
|---|
| Complete response | Stable Disease | Partial Response | Relapse and Progression |
|---|
| DL1 (Ixazomib 2.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 1 | 2 | 0 | 0 |
,| DL2 (Ixazomib 3.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 2 | 0 | 0 | 1 |
,| DL3/MTD (Ixazomib 4.0 mg + Lenalidomide 20 mg + Rituximab 375mg/m2) | 2 | 3 | 1 | 1 |
,| Expansion Cohort 2: Non-Follicular Lymphoma at MTD | 0 | 0 | 0 | 0 |
,| Expansion Cohort I: Follicular Lymphoma at MTD | 5 | 0 | 0 | 0 |
Number of Participants With Adverse Events
For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate. (NCT02903381)
Timeframe: Baseline to 2 Years
| Intervention | Participants (Count of Participants) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 8 |
Objective Response Percent
The percent of patients with objective response defined as achieving a partial response or better according to the modified International Myeloma Working Group (IMWG) criteria (NCT02903381)
Timeframe: 2 Years
| Intervention | percentage of participants (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 87.5 |
Progression Free Survival (PFS) Probability at 2-years
Kaplan-Meier method, percent of patients alive and progression-free at 2-years (NCT02903381)
Timeframe: Baseline to disease progression or death from any cause, censored at date last known progression free for those who have not progressed or died, up to 24 months post initiation of therapy.
| Intervention | probability (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 0.75 |
Progression Free Survival Rate-Without Cyclophosphamide
It is expected that approximately 20% of the patients will receive cyclophosphamide (CTX) for mobilization and this may influence the PFS. Therefore, in a secondary analysis the 2 year PFS rate will be evaluated among those patients who did not receive CTX. (NCT02903381)
Timeframe: 2 Years
| Intervention | percentage of participants (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 71.4 |
Time to Progression Probability at 2-years
Time to progression (TTP) is defined as the time from protocol therapy initiation until documented progression, censored at date last known progression-free for those who have not progressed, up to 24 months post initiation of therapy. (NCT02903381)
Timeframe: Baseline to documented progression, up to 24 months post initiation of therapy.
| Intervention | probability (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 0.75 |
Overall Survival Probability at 2-years
Kaplan-Meier method, percent alive at 2-years (NCT02903381)
Timeframe: Baseline to death or date last known alive, up to 24 months post initiation of therapy.
| Intervention | probability (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 1.0 |
2 Year Progression Free Percent
The primary endpoint will be the 2-year progression-free percent and will be reported with corresponding 90% confidence interval. All patients who have received one dose of study treatment will be included for the analysis, including those who die or are lost to follow-up before 2 years. Progression is defined as ≥ 25% increase and an absolute increase of ≥ 0.5g/dL from their nadir in their serum or urine m-spike or FLC with no CRAB features attributable to MM progression. (NCT02903381)
Timeframe: 2 Year
| Intervention | percentage of participants (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 62.5 |
Duration of Response Probability at 2-years
Kaplan-Meier method, duration of response probability in patients with partial response or better. Events defined as confirmed progression or death from any cause (NCT02903381)
Timeframe: time from objective response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died, up to 24 months post initiation of therapy.
| Intervention | probability (Number) |
|---|
| Nivolumab, Lenalidomide, Dexamethasone | 0.71 |
Evaluation of Stringent Complete Response, Complete Response, and Very Good Partial Response Rate (sCR + CR + VGPR Rate).
Assessed by the investigator per International Myeloma Working Group criteria(IMWG) uniform response criteria. Result reflects number of participants whose best overall response qualified as sCR, CR, or VGPR in 2 year follow up period. (NCT02906332)
Timeframe: Every 3 weeks (day 1 of every 21-day treatment cycle +/- 7 days) through 12 weeks.
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Lenalidomide | 11 |
Number of Participants Serious Adverse Events
Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received pembrolizumab (MK-3475), lenalidomide and dexamethasone, including serious adverse events (SAEs). Result reflects count of participants who experienced an SAE. (NCT02906332)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Lenalidomide | 1 |
Number of Participants Who Progressed at 12 Months
Assessed at 12 months; Subjects without documented PD or death will be censored at the last disease assessment date. Those who died without documented PD will be censored at the time of death. Result reflects count of participants who had progressed at 12 months. (NCT02906332)
Timeframe: Time from Day 0 (transplant) and date of enrollment to study completion (through 12 weeks) by investigator assessment.
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Lenalidomide | 10 |
Progression Free Survival (PFS)
PFS will be assessed from the date of ASCT, with day 0 defined as date of stem cell infusion (if tandem transplant the 2nd of 2 transplants will be used) until the date of progression, defined as the date at which the patient starts the next line of therapy or the date of death. (NCT02906332)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Pembrolizumab + Lenalidomide | 27.6 |
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | Participants (Count of Participants) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 34 |
Overall Response Rate (ORR)
ORR:percentage of participants with CR including stringent complete response(sCR),VGPR,partial response(PR) per independent review committee(IRC)by IMWG criteria.CR: serum,urine -ve immunofixation; disappearance of soft tissue plasmacytomas,<5%plasma cells in bone marrow(CR in those with only measurable disease by serum FLC levels=normal FLC ratio 0.26 to 1.65+CR criteria).sCR:CR+normal FLC ratio,absence of clonal plasma cells(immunohistochemistry)or 2-to 4-color flow cytometry.VGPR:serum,urine M-protein detectable by immunofixation,not by electrophoresis or ≥90%reduction,<100mg/24hrs(VGPR in those with only measurable disease by serum FLC levels,requires>90%decrease in involved-uninvolved FLC level difference).PR: ≥50%reduction of serum M protein+reduction in 24-hr urinary M protein by≥90%/ to<200mg/24-hr or ≥50%decrease in difference between involved-uninvolved FLC levels/≥50%reduction in bone marrow plasma cells,if≥30%at baseline/≥50%soft tissue plasmacytoma size reduction. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 84.4 |
Overall Survival (OS)
OS was defined as the time from the date of first study drug administration to the date of death. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | months (Median) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | NA |
Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR)
Response was assessed using International Myeloma Working Group (IMWG) Criteria. CR was defined as negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | percentage of participants (Number) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 50.0 |
Duration of Response (DOR)
DOR was measured as time in months from date of first documentation of response, VGPR or better, and ORR (CR+PR (including sCR and VGPR) or better, to date of first documented PD among participants who responded to treatment. Response was assessed by investigator using IMWG Criteria. CR:negative immunofixation in serum and urine and; disappearance of any soft tissue plasmacytomas and;<5% plasma cells in bone marrow. sCR:CR plus normal FLC ratio, absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry. VGPR:serum and urine M-protein detectable by immunofixation but not on electrophoresis/≥90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hours. PR:≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved FLC levels/≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/≥50% reduction in size of soft tissue plasmacytomas. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | months (Median) |
|---|
| VGPR or better | ORR |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | NA | 21.65 |
Time to Progression (TTP)
TTP was measured as the time in months from the first dose of study treatment to the date of the first documented PD as assessed using IMWG criteria. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dL); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase > 10 mg/dL); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) attributed solely to plasma cell proliferative disease. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | months (Median) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 22.57 |
Progression-free Survival (PFS)
PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of PD or death from any cause, whichever occurred first. PD required one of the following: increase of ≥ 25% from nadir in: serum M-component (absolute increase ≥ 0.5 g/dl); urine M-component (absolute increase ≥ 200 mg/24 hours); in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 10 mg/dl); development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease. (NCT02917941)
Timeframe: Up to approximately 33 months
| Intervention | months (Median) |
|---|
| Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg | 22.05 |
Dose Escalation Phase: Maximum Tolerated Dose (MTD) of TAK-659
MTD was defined as the maximum dose that is determined to be safe and tolerable in different cohorts. Each cohort (A, B, C, D and E) received different escalating doses of TAK-659 in combination with other drugs. For each cohort the maximum tolerated dose of TAK-659 in combination with the other drug/s from the selected dose range is reported. (NCT02954406)
Timeframe: Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E - each cycle was of 28 days)
| Intervention | mg (Number) |
|---|
| Dose Escalation Phase Cohort A: TAK-659 60-100 mg + Bendamustine 90 mg/m^2 | NA |
| Dose Escalation Phase Cohort B: TAK-659 60-100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | NA |
| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | NA |
| Dose Escalation Phase Cohort D: TAK-659 40-60 mg + Lenalidomide 25 mg | NA |
| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | NA |
Time to Progression (TTP)
TTP was defined as the time from the date of first drug administration to the date of first documented PD. PD was defined as any new lesion or increase by >50% of previously involved sites from nadir. (NCT02954406)
Timeframe: Up to 123 weeks
| Intervention | months (Median) |
|---|
| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 4.2 |
| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 2.7 |
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | 9.6 |
| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 2.6 |
| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 4.2 |
| Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 1.3 |
| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | 1.4 |
| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 3.4 |
| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | NA |
| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | 2.7 |
Tmax: Time to Reach the Maximum Plasma Concentration for TAK-659
(NCT02954406)
Timeframe: Days 1 and 15: Pre-dose and at multiple time points (up to 24 hours) post-dose in Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E - each cycle was of 28 days)
| Intervention | hours (h) (Median) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | 4.00 | 3.83 |
,| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 4.00 | 4.00 |
,| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 2.03 | 1.09 |
,| Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 2.00 | 2.47 |
,| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 1.10 | 1.17 |
,| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 2.00 | 1.93 |
,| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | 4.13 | 2.76 |
,| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 0.6 | 1.9 |
,| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | 2.12 | 2.08 |
,| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | 1.00 | 1.01 |
Cmax: Maximum Observed Plasma Concentration for TAK-659
(NCT02954406)
Timeframe: Days 1 and 15: Pre-dose and at multiple time points (up to 24 hours) post-dose in Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E - each cycle was of 28 days)
| Intervention | nanograms(ng)/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | 118.10 | 187.73 |
,| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 83.61 | 126.49 |
,| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 89.74 | 145.03 |
,| Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 180.10 | 223.53 |
,| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 128.58 | 158.28 |
,| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 142.84 | 222.96 |
,| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | 141.27 | 303.34 |
,| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 139.00 | 188.00 |
,| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | 65.03 | 202.90 |
,| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | 120.23 | 306.59 |
Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of TAK-659
The RP2D was the MTD or less. The dose recommended for use in phase 2 studies was analyzed on the basis of the safety, tolerability, and preliminary pharmacokinetic (PK) and efficacy data obtained in phase 1 studies. Each cohort (A, B, C, D and E) received different escalating doses of TAK-659 in combination with other drugs. For each cohort the recommended Phase 2 dose of TAK-659 in combination with the other drug/s from the selected dose range is reported. (NCT02954406)
Timeframe: Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E each cycle was of 28 days)
| Intervention | mg (Number) |
|---|
| Dose Escalation Phase Cohort A: TAK-659 60-100 mg + Bendamustine 90 mg/m^2 | NA |
| Dose Escalation Phase Cohort B: TAK-659 60-100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 60 |
| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | NA |
| Dose Escalation Phase Cohort D: TAK-659 40-60 mg + Lenalidomide 25 mg | NA |
| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | NA |
AUCtau: Area Under the Plasma Concentration-time Curve During Dosing Interval
(NCT02954406)
Timeframe: Days 1 and 15: Pre-dose and at multiple time points (up to 24 hours) post-dose in Cycle 1 (Cohorts A, B and C - each cycle was of 21 days and Cohorts D and E - each cycle was of 28 days)
| Intervention | h×ng/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | 1532.34 | 3050.97 |
,| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 1094.51 | 1845.21 |
,| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 1011.49 | 1675.91 |
,| Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 1444.89 | 2662.16 |
,| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 852.36 | 1896.76 |
,| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 1455.92 | 2788.61 |
,| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | 387.54 | 3251.29 |
,| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 1456.03 | 2536.48 |
,| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | 758.76 | 2578.30 |
,| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | 968.82 | 4218.90 |
Overall Response Rate (ORR)
ORR was defined as the percentage of participants in the response-evaluable population who achieved either complete response (CR), or partial response (PR). CR was defined as the disappearance of all evidence of disease, and PR was defined as regression of measurable disease and no new sites. (NCT02954406)
Timeframe: Up to 123 weeks
| Intervention | percentage of participants (Number) |
|---|
| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 33.3 |
| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 75.0 |
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | 50.0 |
| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 40.0 |
| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 80.0 |
| Dose Escalation Phase Cohort B: TAK-659 100 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 0.0 |
| Dose Escalation Phase Cohort C: TAK-659 60 mg + Gemcitabine 1000 mg/m^2 | 0.0 |
| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 100.0 |
| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | 33.3 |
| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | 50.0 |
Duration of Response (DOR)
DOR was defined as the time from the date of first documented response to the date of first documented PD. PD was defined as any new lesion or increase by > 50% of previously involved sites from nadir. (NCT02954406)
Timeframe: Up to 123 weeks
| Intervention | months (Median) |
|---|
| Dose Escalation Phase Cohort A: TAK-659 60 mg + Bendamustine 90 mg/m^2 | 2.3 |
| Dose Escalation Phase Cohort A: TAK-659 80 mg + Bendamustine 90 mg/m^2 | 2.8 |
| Dose Escalation Phase Cohort A: TAK-659 100 mg + Bendamustine 90 mg/m^2 | NA |
| Dose Escalation Phase Cohort B: TAK-659 60 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | NA |
| Dose Escalation Phase Cohort B: TAK-659 80 mg + Bendamustine 90 mg/m^2 + Rituximab 375 mg/m^2 | 3.9 |
| Dose Escalation Phase Cohort D: TAK-659 40 mg + Lenalidomide 25 mg | 1.8 |
| Dose Escalation Phase Cohort D: TAK-659 60 mg + Lenalidomide 25 mg | NA |
| Dose Escalation Phase Cohort E: TAK-659 60 mg + Ibrutinib 560 mg | NA |
Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage
Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome. (NCT03003520)
Timeframe: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
| Intervention | percentage of participants (Number) |
|---|
| High Group for PDL1 % of Total Cells | 75 |
| Low Group for PDL1 % of Total Cells | 20 |
Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data
Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome. (NCT03003520)
Timeframe: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
| Intervention | percentage of participants (Number) |
|---|
| High Group for RNA IFN Gamma Score | 43 |
| Low Group for RNA IFN Gamma Score | 60 |
Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy
The primary efficacy analysis evaluated the complete response rate (CRR) at the end of the induction therapy in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined as a complete metabolic response and radiographic evidence showing target nodes/nodal masses regressed to ≤ 1.5 cm in longest diameter, no new lesions, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis for the primary endpoint was rejected if the lower limit of the confidence interval for the complete response rate at the completion of the induction therapy in the efficacy evaluable population is above 55%. (NCT03003520)
Timeframe: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
| Intervention | percentage of participants (Number) |
|---|
| DUR + R-CHOP | 54.1 |
| DUR + R2-CHOP | 66.7 |
Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018)
The percentage of participants who achieved a partial response (PR) or complete response (CR) at the end of Induction and continued into consolidation period in the efficacy evaluable population in a comparative manner against historical control. The response to treatment was assessed according to the 2014 International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) (Cheson, 2014). CR was defined in outcome #1. PR was defined as a partial metabolic response and radiographic evidence showing ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites, no new lesions, spleen must have regressed > 50% in length beyond normal, and residual bone marrow involvement improved from baseline. Clopper-Pearson two-sided 95% confidence interval is reported. Null hypothesis was rejected if the lower limit of the confidence interval for the rate of subjects who continue consolidation therapy out of all subjects. (NCT03003520)
Timeframe: From first dose of study drug to completion of at least one cycle in the Consolidation Period (Day 1 up to Week 52)
| Intervention | percentage of participants (Number) |
|---|
| DUR + R-CHOP | 67.6 |
| DUR + R2-CHOP | 66.7 |
Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density
Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome. (NCT03003520)
Timeframe: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
| Intervention | percentage of participants (Number) |
|---|
| High Group for CD8 Density | 67 |
| Low Group for CD8 Density | 64 |
Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells
Data in the analysis include all participants who received durvalumab, irrespective of the study arm in which they enrolled, because the selected biomarkers have been associated with response in other anti-PD1 or anti-PDL1 studies, such as durvalumab. IHC analysis was performed on the baseline tumor biopsy to quantify CD8 T-cell density. Participants with 'high' values, i.e. above the threshold defined as the median value of 774 cells/mm^2 found in commercial DLBCL samples using matched analytical methods, were predicted to be responders to treatment with durvalumab. The definition of a complete response was that used in the primary outcome. (NCT03003520)
Timeframe: Biomarker biopsies: Days -28 to Day -1. Clinical response: From first dose of study drug to end of Induction therapy (Day 1 up to Week 26 - maximum duration of Induction Period).
| Intervention | percentage of participants (Number) |
|---|
| High Group for PDL1 % of Tumor Cells | 64 |
| Low Group for PDL1 % of Tumor Cells | 56 |
Participants With Treatment Emergent Adverse Events (TEAE)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator. (NCT03003520)
Timeframe: From the date of the first dose of study drug to within 90 days after the last dose of durvalumab or 28 days after the last dose of any investigational product (IP) whichever is greater. (Up to approximately 72 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| >= 1 Treatment-emergent adverse event (TEAE) | >=1 TEAE related to durvalumab | >=1 TEAE related to R-CHOP | >=1 TEAE related to durvalumab or any other IP | >=1 TEAE severity grade 3-4 | >=1 TEAE severity grade 3-4 related to durvalumab | >=1 TEAE severity grade 3-4 related to R-CHOP | >=1 TEAE severity grade 3-4 related to any IP | >=1 TEAE severity grade 5 | >=1 TEAE severity grade 5 related to any IP | >=1 serious TEAE | >=1 serious TEAE related to durvalumab | >=1 serious TEAE related to R-CHOP | >=1 serious TEAE related to any IP | >=1 leading to discontinuation of durvalumab | >=1 leading to discontinuation of R-CHOP | >=1 leading to discontinuation of any IP | >=1 leading to interruption of durvalumab | >=1 leading to interruption of R-CHOP | >=1 leading to interruption of any IP | >=1 leading to infusion interruption of durvalumab | >=1 leading to dose reduction of vincristine |
|---|
| DUR + R-CHOP | 43 | 33 | 40 | 41 | 37 | 18 | 27 | 31 | 3 | 0 | 23 | 10 | 10 | 14 | 13 | 4 | 13 | 15 | 12 | 18 | 2 | 4 |
Participants With Treatment Emergent Adverse Events (TEAE)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild (no limitation in activity or intervention); - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); - Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); - Grade 4 = Life-threatening; - Grade 5 = Death. Relation to IP is determined by the investigator. (NCT03003520)
Timeframe: From the date of the first dose of study drug to within 90 days after the last dose of durvalumab or 28 days after the last dose of any investigational product (IP) whichever is greater. (Up to approximately 72 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| >= 1 Treatment-emergent adverse event (TEAE) | >=1 TEAE related to durvalumab | >=1 TEAE related to R-CHOP | >=1 TEAE related to lenalidomide | >=1 TEAE related to durvalumab or any other IP | >=1 TEAE severity grade 3-4 | >=1 TEAE severity grade 3-4 related to durvalumab | >=1 TEAE severity grade 3-4 related to R-CHOP | >=1 TEAE severity grade 3-4 related to lenalidomid | >=1 TEAE severity grade 3-4 related to any IP | >=1 TEAE severity grade 5 | >=1 TEAE severity grade 5 related to any IP | >=1 serious TEAE | >=1 serious TEAE related to durvalumab | >=1 serious TEAE related to R-CHOP | >=1 serious TEAE related to lenalidomide | >=1 serious TEAE related to any IP | >=1 leading to discontinuation of durvalumab | >=1 leading to discontinuation of R-CHOP | >=1 leading to discontinuation of lenalidomide | >=1 leading to discontinuation of any IP | >=1 leading to interruption of durvalumab | >=1 leading to interruption of R-CHOP | >=1 leading to interruption of lenalidomide | >=1 leading to interruption of any IP | >=1 leading to infusion interruption of durvalumab | >=1 leading to dose reduction of vincristine | >=1 leading to dose reduction of lenalidomide |
|---|
| DUR + R2-CHOP | 3 | 3 | 3 | 3 | 3 | 3 | 1 | 3 | 2 | 3 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 2 | 3 | 0 | 1 | 1 |
Number of Participants Who Survived
Number of Participants Who Survived at day 180. (NCT03019640)
Timeframe: From the time of transplant, assessed up to day 180
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, NK Infusion, Stem Cell Transplant) | 16 |
Total Number of Adverse Events
Collect and grade all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant. (NCT03050450)
Timeframe: Two 28 day cycles
| Intervention | total adverse events (Number) |
|---|
| Grade 1 adverse events | Grace 2 adverse events | Grade 3 adverse events | Grade 4 adverse events | Grade 5 adverse events |
|---|
| Dose Level 1 | 68 | 32 | 12 | 2 | 1 |
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors
Best response by MRIs per definitions in the protocol (complete response, partial response, stable disease, progressive disease). MRI's were obtained every 2 cycles and the best response was reported. (NCT03050450)
Timeframe: Every 2 cycles up to 24 cycles
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease |
|---|
| Dose Level 1 | 0 | 1 | 1 | 2 |
Number Participants With Hematologic and Non-hematologic Toxicities
Number participants with grades 3 to 5 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2. (NCT03050450)
Timeframe: Two 28 day cycles
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 & 4 Blood/Bone Marrow | Grade 3 & 4 Gastrointestinal | Grade 3 & 4 Metabolic/Laboratory | Grade 3 & 4 Musculoskelatal/Soft Tissue | Grade 3 & 4 Neurology | Grade 3 & 4 Pain | Grade 3 & 4 Vascular | Grade 3 & 4 & 5 Other |
|---|
| Dose Level 1 | 0 | 2 | 5 | 1 | 1 | 0 | 0 | 6 |
Transfusion Support: Number of Red Blood Cell and Platelet Transfusions
Number of red blood cell and platelet transfusions received within the first 50 days of treatment (NCT03118466)
Timeframe: 50 days
| Intervention | Number of Transfusions (Median) |
|---|
| Platelet Transfusions | Red Blood Cell Transfusions |
|---|
| Lenalidomide and MEC Chemotherapy | 7 | 9 |
Overall Survival
Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive. (NCT03118466)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Lenalidomide and MEC Chemotherapy | 16 |
Number of Patients That Achieved Platelet Recovery
The number of patients that achieved a stable platelet count > 20,000/mm3 for 3 days within 45 days of starting treatment (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 27 |
Number of Patients That Achieved ANC Recovery
The number of patients that achieved a neutrophil count of > 500/mm3 for 3 days within 45 of starting treatment (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 25 |
Complete Response Rate
"Proportion of patients who have achieve CR or CRp after treatment.~Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC >1000/mm3 and platelet count >100,000/mm3.~Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count < 100,000/mm3 (CRp)." (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 19 |
Overall Survival
Overall survival is defined as the time from date of study enrollment until death from any cause. (NCT03224507)
Timeframe: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 108 |
Percentage of Patients Achieving Complete Remission Following Complete Therapy
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. Complete therapy incorporates induction and consolidation therapy. (NCT03224507)
Timeframe: Baseline up to 15 months
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 106 |
Serious Adverse Events (SAEs) From the KRdD Treatment
The Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used for this assessment. SAEs include events that are Grade 3 and above; non-serious events are Grades 1-2. (NCT03224507)
Timeframe: Baseline until the progression of disease or MRD(-) status up to an estimated 15 months.
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 14 |
Percentage of Patients With MRD(-) Status at the Completion of Induction Therapy
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. (NCT03224507)
Timeframe: Baseline until MRD(-) status estimated at 6 months or until disease progression
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 45 |
Progression-free Survival
Progression-free survival is defined as the interval from the start of therapy to the earliest occurrence of the following: disease progression, initiation of anti-myeloma therapy that is not an accepted maintenance therapy of lenalidomide or death from any cause. Kaplan-Meier methods will used. (NCT03224507)
Timeframe: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 90 |
Percentage of Patients With MRD(-) Remissions at the Completion of Consolidation Therapy
The primary endpoint of MRD(-) rate, or percentage of patients with MRD(-) remissions, will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. (NCT03224507)
Timeframe: Baseline until MRD(-) is reached estimated to be up to 15 months.
| Intervention | percentage of patients achieving MRD (-) (Number) |
|---|
| KRdD Followed by Auto-HCT | 81.4 |
Percentage of Patients With Auto-HCT That Convert From Positive to Negative MRD
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. (NCT03224507)
Timeframe: From baseline up to an estimated 9 months
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 32 |
Percentage of Patients That Convert From MRD(-) to MRD(+) Following Treatment Discontinuation
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. (NCT03224507)
Timeframe: Baseline to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| KRdD Followed by Auto-HCT | 23 |
Overall Response
Overall response with elotuzumab and lenalidomide for each study arm. Overall Response is defined as best Overall Response, as Complete Response or Partial Response. Response will be assessed per the uniform response criteria of the International Myeloma Working Group(IMWG). Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. Complete Response= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates; Partial Response= ≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by ≥90% or to <200 mg per 24 h; (NCT03411031)
Timeframe: Up to 60 days post last study treatment
| Intervention | Participants (Count of Participants) |
|---|
| A: Elotuzumab + Lenalidomide at 25 mg | 1 |
| B: Elotuzumab + Lenalidomide at 10 mg | 2 |
Minimum Response (MR)
Minimum response (MR) or better with elotuzumab and lenalidomide for each study arm. The Consensus on Uniform Reporting of Response will be used to evaluate response. Myeloma participants enrolled in this clinical study will be assessed for disease response after every cycle. (NCT03411031)
Timeframe: Up to 60 days post last study treatment
| Intervention | Participants (Count of Participants) |
|---|
| A: Elotuzumab + Lenalidomide at 25 mg | 2 |
| B: Elotuzumab + Lenalidomide at 10 mg | 3 |
Percentage of Participants With Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the time of randomization to date of death from any cause, date of relapse/progression, or the last follow-up date, whichever comes first. The Kaplan-Meier method will be used to estimate PFS for each Study Arm. The method of Brookmeyer and Crowley will be used to construct 95% confidence interval. (NCT03411031)
Timeframe: An average of 8 months
| Intervention | percentage of participants (Number) |
|---|
| A: Elotuzumab + Lenalidomide at 25 mg | 11.1 |
| B: Elotuzumab + Lenalidomide at 10 mg | 22.2 |
Percentage of Participants With Anti-Daratumumab Antibodies
Percentage of participants with antibodies to daratumumab were reported. (NCT03412565)
Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 0 |
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 0 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 0 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 0 |
D-VRd Cohort: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved a PR or better, IMWG criteria, during the study or during follow up. IMWG criteria for PR >= 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required. (NCT03412565)
Timeframe: Up to 2 years and 3 months
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 97.0 |
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. (NCT03412565)
Timeframe: From baseline up to 2 years 7 months
| Intervention | percentage of participants (Number) |
|---|
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 77.6 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 80.0 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 77.3 |
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
MRD negativity rate was defined as the percentage of participants who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5. (NCT03412565)
Timeframe: Up to 2 years and 3 months
| Intervention | percentage of participants (Number) |
|---|
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 25.4 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 21.5 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 27.3 |
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. (NCT03412565)
Timeframe: Up to 2 years and 3 months
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 71.6 |
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days. (NCT03412565)
Timeframe: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 Day 4 | Cycle 3 Day 4 |
|---|
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 108 | 648 |
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days. (NCT03412565)
Timeframe: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 Day 4 | Cycle 2 Day 4 | Post-treatment Phase Week 8 |
|---|
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 98.6 | 612 | 162 |
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days. (NCT03412565)
Timeframe: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 Day 4 | Cycle 3 Day 4 | Post-treatment Phase Week 8 |
|---|
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 137 | 869 | 49.3 |
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days. (NCT03412565)
Timeframe: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 Day 4 | Cycle 4 Day 4 | Post-treatment Phase Week 8 |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 100 | 746 | 263 |
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required. (NCT03412565)
Timeframe: Up to 2 years 3 months
| Intervention | percentage of participants (Number) |
|---|
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 88.1 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 90.8 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 84.8 |
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
DOR was defined as the time from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death due to PD. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder. (NCT03412565)
Timeframe: From baseline up to 2 years 7 months
| Intervention | months (Median) |
|---|
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | NA |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | NA |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | NA |
Percentage of Participants With CR or Better Response
CR or better rate was defined as the percentage of participants with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. (NCT03412565)
Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 16.4 |
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 55.2 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 50.8 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 42.4 |
Percentage of Participants With Anti-rHuPH20 Antibodies
Percentage of participants with antibodies to rHuPH20 were reported. (NCT03412565)
Timeframe: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | 6.1 |
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | 3.1 |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | 4.8 |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | 4.7 |
Percentage of Participants With Bone Lesions (Bone Evaluation)
(NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 100.0 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 59.1 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 64.0 |
Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)
VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 33.3 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 43.6 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 42.2 |
Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment
(NCT03416374)
Timeframe: 12 months
| Intervention | Percentage of Participants (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 50.0 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 35.9 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 37.8 |
Overall Survival (OS) From the Start of Study Treatment
OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Months (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | NA |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | NA |
| [Overall]; Combination Therapy + Ixazomib Therapy | NA |
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 83.3 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 71.8 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 73.3 |
Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Participants (Count of Participants) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 6 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 35 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 41 |
Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Number of Events per Participants-Month (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 1.9 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 2.9 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 2.7 |
Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants
HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Days (Mean) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 14.8 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 19.4 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 18.8 |
Duration of Therapy (DOT)
DOT is defined as the treatment duration of study drug at study treatment Period I. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Months (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 14.69 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 12.43 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 12.43 |
Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Months (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 15.31 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 28.03 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 28.03 |
Evaluation of Modified Quality-Adjusted Life-Years (QALYs)
Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Quality-Adjusted Life-Years (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 0.467 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 0.534 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 0.518 |
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR
MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10^-4 to - Max; 10^-5 to 10^-4; 10^-6 to 10^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Participants (Count of Participants) |
|---|
| Sensitivity Level; 10^-4=< - Max | Sensitivity Level; 10^-5=< - <10^-4 | Sensitivity Level; 10^-6=< - <10^-5 | Negative |
|---|
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 1 | 2 | 1 | 5 |
,| [Overall]; Combination Therapy + Ixazomib Therapy | 1 | 3 | 2 | 5 |
,| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 0 | 1 | 1 | 0 |
Time to Next Treatment (TTNT)
TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Months (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 21.59 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 32.26 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 32.26 |
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03416374)
Timeframe: Up to 12 months
| Intervention | Percentage of Participants (Number) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 50.0 |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 48.7 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 48.9 |
PFS From the Start of Study Treatment
PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Months (Median) |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | NA |
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 28.96 |
| [Overall]; Combination Therapy + Ixazomib Therapy | 28.96 |
Percentage of Participants Who Achieve or Maintain Any Best Response
Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| CR | VGPR | PR |
|---|
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 23.1 | 20.5 | 28.2 |
,| [Overall]; Combination Therapy + Ixazomib Therapy | 24.4 | 17.8 | 31.1 |
,| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 33.3 | 0 | 50.0 |
Relative Dose Intensity (RDI)
RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles]. (NCT03416374)
Timeframe: Up to 39 months as a maximum
| Intervention | Percent (Median) |
|---|
| Bortezomib, Ixazomib | Carfilzomib, Ixazomib | Bortezomib/Carfilzomib, Ixazomib | Lenalidomide | Dexamethasone |
|---|
| [Overall]; Combination Therapy + Ixazomib Therapy | 71.93 | 87.70 | 83.24 | 47.18 | 48.61 |
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening. (NCT03416374)
Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)
| Intervention | Score on a Scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: Cycle 23 | Side-Effects of Treatment: Baseline | Side-Effects of Treatment: Cycle 23 | Body Image: Baseline | Body Image: Cycle 23 | Future Perspective: Baseline | Future Perspective: Cycle 23 |
|---|
| [VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy | 24.07 | 0 | 16.67 | 3.70 | 44.44 | 0 | 66.67 | 11.11 |
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening. (NCT03416374)
Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)
| Intervention | Score on a Scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: Cycle 23 | Disease Symptoms: Cycle 32 | Side-Effects of Treatment: Baseline | Side-Effects of Treatment: Cycle 23 | Side-Effects of Treatment: Cycle 32 | Body Image: Baseline | Body Image: Cycle 23 | Body Image: Cycle 32 | Future Perspective: Baseline | Future Perspective: Cycle 23 | Future Perspective: Cycle 32 |
|---|
| [KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy | 19.23 | 4.63 | 2.78 | 16.60 | 16.05 | 18.52 | 23.08 | 16.67 | 16.67 | 44.16 | 35.19 | 27.78 |
,| [Overall]; Combination Therapy + Ixazomib Therapy | 19.88 | 3.97 | 2.78 | 16.61 | 14.29 | 18.52 | 25.93 | 14.29 | 16.67 | 47.16 | 31.75 | 27.78 |
Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Participants (Count of Participants) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 249 |
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 53.9 |
Overall Survival (OS)
OS is defined as the period from the start of IRd therapy in standard medical care to the time when death (regardless of the cause of death) is confirmed. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Months (Median) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 20.23 |
Percentage of Participants Who Achieve VGPR or Better (CR+VGPR)
The percentage of participants of CR + VGPR is defined as the rate of participants who achieve a best response of VGPR or better (sCR, CR, or VGPR) according to the IMWG Criteria after the start of the IRd therapy. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 31.5 |
Percentage of Participants With Bone Lesions (Bone Evaluation)
(NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 21.5 |
Time to Next Treatment (TTNT)
TTNT will be measured as the period from the start of IRd therapy in standard medical care to the start of next treatment or time when death is confirmed (regardless of the cause of death), whichever is earlier. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Months (Median) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 5.02 |
Relative Dose Intensity (RDI)
RDI is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles]. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percent (Mean) |
|---|
| Ixazomib | Lenalidomide | Dexamethasone |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 66.49 | 44.72 | 41.07 |
Percentage of Participants Who Achieve or Maintain Any Best Response
Best response is defined as the cumulative numbers of participants who achieve each level of best response including partial response (PR), very good PR (VGPR) and complete response (CR) assessed with IMWG Criteria after each cycle of treatment. Per IMWG criteria, PR: ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum+urine +disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| CR | VGPR | PR |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 20.0 | 8.5 | 22.0 |
Percentage of Participants Who Continue to Receive Treatment at 12 Months and 24 Months After Start of Treatment
(NCT03433001)
Timeframe: 12 months and 24 months
| Intervention | Percentage of Participants (Number) |
|---|
| Month 12 | Month 24 |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 40.0 | 21.7 |
Progression-Free Survival (PFS)
PFS was defined as the period from the start of ixazomib, lenalidomide, dexamethasone (IRd) therapy in standard medical care to the time of confirmed progressive disease (PD) or confirmed death (regardless of the cause of death), whichever was earlier. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, PD: serum M-component increase ≥ 0.5 g/dl or urine M-component increase ≥ 200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥ 10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03433001)
Timeframe: Up to 36 Months as a maximum
| Intervention | Months (Median) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 4.79 |
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the future perspective scale, higher score = better perspective of the future. For the body image scale, higher scores = better body image. Higher score for the disease symptoms scale = higher level of symptomatology. (NCT03433001)
Timeframe: Baseline and End of Treatment (Up to 37 cycles, each cycle was of 28 days)
| Intervention | Score on a Scale (Mean) |
|---|
| Disease Symptoms: Baseline | Disease Symptoms: End of Treatment | Side-Effects of Treatment: Baseline | Side-Effects of Treatment: End of Treatment | Body Image: Baseline | Body Image: End of Treatment | Future Perspective: Baseline | Future Perspective: End of Treatment |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 19.33 | 11.11 | 17.80 | 16.67 | 28.18 | 16.67 | 42.49 | 33.33 |
Duration of Therapy (DOT)
DOT is defined as the treatment duration of IRd therapy. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Days (Mean) |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 353.3 |
Rate of Minimal Residual Disease (MRD) Negativity in Bone Marrow in Participants Who Achieved CR
Rate of MRD will be calculated by the percentage of participants who are MRD-negative. (NCT03433001)
Timeframe: Up to 36 months as a maximum
| Intervention | Percentage of Participants (Number) |
|---|
| 10^-4=< - Max | 10^-5=< - <10^-4 | 10^-6=< - <10^-5 | Negative |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 26.7 | 16.7 | 6.7 | 50.0 |
PFS Rate at 12 Months and 24 Months After the Start of Treatment
PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months and 24 months after the date of start of study treatment. PFS was assessed by IMWG Criteria (2014 version). Per IMWG criteria, PD: serum M-component increase ≥ 0.5 g/dl or urine M-component increase ≥ 200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell ≥ 10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia. (NCT03433001)
Timeframe: 12 months and 24 months
| Intervention | Percentage of Participants (Number) |
|---|
| Month 12 | Month 24 |
|---|
| Ixazomib + Lenalidomide + Dexamethasone | 57 | 41 |
Number of Participants Who Achieved Complete Response (CR), Very Good Partial Response (VGPR), and Partial Response (PR)
Number of participants who achieved CR, PR, VGPR were assessed in accordance to International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or greater than or equal to (>=) 90% decrease in serum M-protein with urine M-protein <100 milligram per 24 hours (mg/24 hrs). If disease measurable only by SFLC, >= 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). PR: >= 50% reduction of serum M-protein and >= 90% reduction in urine M-protein or to <200 mg/24 hrs, or a >= 50% decrease in dFLC. A >=50% decrease in the size of soft tissue plasmacytomas present at baseline (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Ixazomib 4.0 mg | 0 |
| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 2 |
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
(NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Ixazomib 4.0 mg | 7 |
| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 7 |
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
DLT:Any following adverse events (AEs) possibly related to ixazomib assessed by Common Terminology Criteria for AEs (CTCAE) version 4.03; Grade 4 neutropenia/thrombocytopenia lasting >7 consecutive days; Grade 3/greater neutropenia with fever/infections; Grade 3/greater thrombocytopenia with clinically significant bleeding; platelet count less than (<)10,000 per cubic meter(/mm^3); Grade 2 peripheral neuropathy with pain/Grade 3 or greater peripheral neuropathy; Grade 3/greater nonhematologic toxicities with exceptions of arthralgia/myalgia, fatigue lasting <7 days manageable nausea/emesis with antiemetic prophylaxis, diarrhea that is controlled with supportive care; treatment delay of >14 days at start of Cycle 2 due to failure of hematologic/nonhematologic recovery; Other Grade 2/greater ixazomib related nonhematologic toxicities required permanent discontinuation of ixazomib;Inability to receive at least 80% of planned lenalidomide doses due to the AEs related to ixazomib. (NCT04272775)
Timeframe: From Cycle 1 Day 1 until Cycle 2 Day 1 (Cycle length is equal to [=] 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Ixazomib 4.0 mg | 1 |
| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 1 |
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Laboratory tests abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Grade 4: Neutrophils low | Grade 4: Leukocytes low | Grade 4: Lymphocytes low | Grade 4: Platelets low | Grade 4: Sodium low | Grade 4: Potassium low | Grade 3: Neutrophils low | Grade 3: Hemoglobin low | Grade 3: Leukocytes low | Grade 3: Lymphocytes low | Grade 3: Platelets low | Grade 3: Albumin low | Grade 3: Corrected calcium high | Grade 3: Sodium low | Grade 3: Potassium low | Grade 3: Phosphate low |
|---|
| Cohort 1: Ixazomib 4.0 mg | 0 | 0 | 3 | 3 | 0 | 0 | 4 | 2 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 1 |
,| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 2 | 1 | 0 | 2 | 1 | 1 | 2 | 2 | 2 | 3 | 2 | 1 | 1 | 0 | 0 | 1 |
Cmax: Maximum Observed Plasma Concentration for Ixazomib
(NCT04272775)
Timeframe: Days 1 and 15 of Cycle 1: pre-dose and at multiple time points (15, 30, 60, and 90 minutes and 2, 4, 8, 24, 48, 96, and 168 hours) post-dose (Cycle length=28 days)
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Day 1 | Day 15 |
|---|
| Cohort 1: Ixazomib 4.0 mg | 65.3 | 68.8 |
,| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 32.9 | 34.5 |
Number of Participants With Grade 3 or Higher TEAE Related to Body Weight
Body weight abnormalities were graded using the CTCAE version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE). (NCT04272775)
Timeframe: Baseline up to 29 days after last dose of study drug (up to Cycle 87 Day 44) (Each Cycle length=28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: Ixazomib 4.0 mg | 0 |
| Cohort 2: Ixazomib 4.0 mg + Lenalidomide and Dexamethasone | 0 |
Overall Response Rate After 4 Cycles Induction Therapy
"Overall response rate will be the percentage of patients who achieve at least partial response (PR) per International Myeloma Working Group (IMWG) Uniform Response criteria after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI).~The IMWG response criteria define a PR as:~> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h, OR If the serum and urine M-protein are unmeasurable, a > 50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, OR If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, > 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was > 30%.~In addition to the above listed criteria, if present at baseline, a > 50% reduction in the size of soft tissue plasmacytomas is also required for a partial response." (NCT04430894)
Timeframe: 112 days (4 cycles)
| Intervention | Participants (Count of Participants) |
|---|
| Induction | 47 |
Minimal Residual Disease (MRD) Rate at 10^(-5) in Patients Receiving Upfront Stem Cell Transplant
MRD is the small number myeloma cells surviving in the bone marrow after a clinical response has been measured and the patient is in remission. MRD negativity will be determined by deep sequencing of genomic deoxyribonucleic acid from bone marrow samples using rearranged Ig locus-specific primers (Adaptive, Seattle, WA). The MRD rate is the percentage of patients who are MRD negative at 10^(-5), meaning that no MRD was detected in a sample of 100,000 cells. MRD status was assessed after 4 cycles of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI) induction, stem cell transplant, and 2 cycles of KRDI consolidation therapy (6 cycles total.) (NCT04430894)
Timeframe: 168 Days (6 cycles, upfront transplant)
| Intervention | percentage of participants (Number) |
|---|
| Upfront Stem Cell Transplant (4 Cycles Induction Therapy, SCT, and 2 Cycles Consolidation Therapy) | 20 |
Minimal Residual Disease (MRD) Rate at 10^(-5) in Patients Deferring Stem Cell Transplant
MRD is the small number myeloma cells surviving in the bone marrow after a clinical response has been measured and the patient is in remission. MRD negativity will be determined by deep sequencing of genomic deoxyribonucleic acid from bone marrow samples using rearranged Ig locus-specific primers (Adaptive, Seattle, WA). The MRD rate is the percentage of patients who are MRD negative at 10^(-5), meaning that no MRD was detected in a sample of 100,000 cells. MRD status was assessed after 4 cycles of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI) induction, stem cell collection, and 4 additional cycles of KRDI (8 cycles total). (NCT04430894)
Timeframe: 224 Days (8 cycles transplant-deferred)
| Intervention | Participants (Count of Participants) |
|---|
| Deferred Stem Cell Transplant (4 Cycles, Stem Cell Collection, 4 Additional Cycles) | 26 |
Complete Response Rate in Patients With Upfront Stem Cell Transplant
"Percentage of patients who achieved a complete response (CR) or stringent CR (sCR) per International Myeloma Working Group (IMWG) Uniform Response criteria after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI), stem cell transplant, and 2 cycles of KRDI consolidation (6 cycles total). IMWG criteria define a CR as Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow and an sCR as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence." (NCT04430894)
Timeframe: 168 Days
| Intervention | percentage of participants (Number) |
|---|
| Upfront Stem Cell Transplant (4 Cycles Induction Therapy, SCT, and 2 Cycles Consolidation Therapy) | 80 |
Complete Response (CR + Stringent CR) Rate
"Percentage of patients who achieved a complete response (CR) or stringent CR (sCR) per International Myeloma Working Group (IMWG) Uniform Response criteria after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI). IMWG criteria define a CR as Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow and an sCR as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence." (NCT04430894)
Timeframe: 112 Days
| Intervention | Participants (Count of Participants) |
|---|
| Induction | 19 |
Overall Survival at 12 Months
Overall survival (OS) is defined as the time between the start of treatment and death due to any cause. OS at 12 months is the percentage of patients who were alive 12 months after initiating treatment with of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI). (NCT04430894)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| Induction | 97.9 |
Progression Free Survival at 12 Months
Progression free survival (PFS) is defined as the time between the start of treatment and disease progression or death due to any cause. PFS at 12 months is the percentage of patients who were alive and without disease progression 12 months after initiating treatment with of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI). (NCT04430894)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| Induction | 97.9 |
Minimal Residual Disease (MRD) Rate After 4 Cycles Induction Therapy
MRD is the small number myeloma cells surviving in the bone marrow after a clinical response has been measured and the patient is in remission. MRD negativity will be determined by deep sequencing of genomic deoxyribonucleic acid from bone marrow samples using rearranged Ig locus-specific primers (Adaptive, Seattle, WA). The MRD rate after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI) is the percentage of patients who are MRD negative at 10^(-5) and 10^(-6), meaning that no MRD was detected in samples of 100,000 cells and 1,000,000 cells, respectively. (NCT04430894)
Timeframe: 112 Days (4 Cycles)
| Intervention | Participants (Count of Participants) |
|---|
| MRD negative at 10^(-5) | MRD negative at 10^(-6) |
|---|
| Induction | 12 | 9 |
Complete Response Rate in Patients Deferring Stem Cell Transplant
"Percentage of patients who achieved a complete response (CR) or stringent CR (sCR) per International Myeloma Working Group (IMWG) Uniform Response criteria after 4 cycles of of Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (KRDI), stem cell collection, and 4 additional cycles of KRDI after deferring stem cell transplant (8 cycles total). IMWG criteria define a CR as Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow and an sCR as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence." (NCT04430894)
Timeframe: 224 Days
| Intervention | percentage of participants (Number) |
|---|
| Deferred Stem Cell Transplant (4 Cycles, Stem Cell Collection, 4 Additional Cycles) | 67 |