| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| A Phase 2 Trial of Leflunomide, Pomalidomide, and Dexamethasone for Relapsed/Refractory Multiple Myeloma [NCT04508790] | Phase 2 | 29 participants (Anticipated) | Interventional | 2020-11-27 | Recruiting |
| An Open Label, Randomized Phase 2 Trial of Pomalidomide/Dexamethasone With or Without Elotuzumab in Relapsed and Refractory Multiple Myeloma (ELOQUENT-3) [NCT02654132] | Phase 2 | 117 participants (Actual) | Interventional | 2016-03-18 | Completed |
| A Phase I/II Study of the Safety, Pharmacokinetics and Efficacy of Pomalidomide (CC-4047) in the Treatment of Kaposi Sarcoma in Individuals With or Without HIV [NCT01495598] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2012-01-10 | Completed |
| A Phase 3 Study Comparing Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor. [NCT03180736] | Phase 3 | 304 participants (Actual) | Interventional | 2017-06-12 | Active, not recruiting |
| A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Thera [NCT05572515] | Phase 3 | 590 participants (Anticipated) | Interventional | 2023-03-29 | Recruiting |
| A Phase 3 Randomized Study Comparing Talquetamab SC in Combination With Daratumumab SC and Pomalidomide (Tal-DP) or Talquetamab SC in Combination With Daratumumab SC (Tal-D) Versus Daratumumab SC, Pomalidomide and Dexamethasone (DPd), in Participants With [NCT05455320] | Phase 3 | 810 participants (Anticipated) | Interventional | 2022-10-13 | 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 Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory [NCT05083169] | Phase 3 | 587 participants (Actual) | Interventional | 2021-10-14 | Active, not 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 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 |
| A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Rela [NCT04181827] | Phase 3 | 419 participants (Actual) | Interventional | 2020-06-12 | Active, not recruiting |
| A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma [NCT04108195] | Phase 1 | 290 participants (Actual) | Interventional | 2020-02-21 | Active, not recruiting |
| A Phase 1 Study of SEA-BCMA in Patients With Relapsed or Refractory Multiple Myeloma [NCT03582033] | Phase 1 | 83 participants (Actual) | Interventional | 2018-11-01 | Terminated(stopped due to Study closed due to portfolio prioritization) |
| Clinical and Pharmacodynamic Comparison of Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma [NCT01319422] | Phase 2 | 40 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Multi-Center Phase 2 Study of Daratumumab With Pomalidomide and Dexamethasone in Combination With All-Transretinoic Acid in Patients With Multiple Myeloma Previously Exposed to Daratumumab-Based Regimens [NCT04700176] | Phase 2 | 43 participants (Anticipated) | Interventional | 2022-05-02 | Recruiting |
| Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Pomalidomide, Dexamethasone, and Carfilzomib (PdC) in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma [NCT01665794] | Phase 1/Phase 2 | 101 participants (Anticipated) | Interventional | 2012-08-13 | Recruiting |
| Multicenter Study of Pomalidomide, Cyclophosphamide, and Dexamethasone in Relapsed Refractory Myeloma: Safety Profile in Mexican Population [NCT03601624] | Phase 2 | 18 participants (Anticipated) | Interventional | 2018-09-01 | Recruiting |
| A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide With or Without Pomalidomide in Patients With Relapsed and Refractory Multiple Myeloma [NCT03215524] | Phase 2 | 120 participants (Actual) | Interventional | 2017-10-25 | 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 |
| A Single-Arm Phase II Study of Isatuximab With Carfilzomib and Pomalidomide in Relapsed or Refractory Multiple Myeloma [NCT04850599] | Phase 2 | 5 participants (Actual) | Interventional | 2022-06-14 | Active, not recruiting |
| A MULTICENTER, OPEN LABEL, RANDOMIZED PHASE III STUDY OF POMALIDOMIDE-DEXAMETHASONE vs POMALIDOMIDE-CYCLOPHOSPHAMIDE-DEXAMETHASONE IN MULTIPLE MYELOMA (MM) PATIENTS WHO EXPERIENCE BIOCHEMICAL OR CLINICAL RELAPSE DURING LENALIDOMIDE MAINTENANCE TREATMENT [NCT03440411] | Phase 3 | 9 participants (Actual) | Interventional | 2016-02-18 | Terminated(stopped due to Low enrollment) |
| A Phase 2B Study of Selinexor (KPT-330), in Combination With Carfilzomib, Daratumumab or Pomalidomide in Patients With Multiple Myeloma Relapsing on Current Therapy [NCT04661137] | Phase 2 | 96 participants (Anticipated) | Interventional | 2021-03-16 | Recruiting |
| An Open-label Phase I/II Trial of Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Systemic Light-Chain Amyloidosis [NCT05451771] | Phase 1/Phase 2 | 53 participants (Anticipated) | Interventional | 2022-10-26 | Recruiting |
| A Phase Ib Investigation of the Safety and Efficacy of ABI-009 (Nab-rapamycin) in Combination With Pomalidomide and Dexamethasone for Relapsed and Refractory Multiple Myeloma [NCT03657420] | Phase 1 | 0 participants (Actual) | Interventional | 2019-05-30 | Withdrawn(stopped due to Funding withdrawn by sponsor) |
| A Phase 1 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Glutaminase Inhibitor CB-839 in Patients With Advanced and/or Treatment-Refractory Hematological Malignancies [NCT02071888] | Phase 1 | 25 participants (Actual) | Interventional | 2014-02-28 | Completed |
| A Multicenter, Single-arm, Open-label Study With Pomalidomide in Combination With Low Dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma [NCT01712789] | Phase 3 | 682 participants (Actual) | Interventional | 2012-11-06 | Completed |
| A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myelom [NCT04045795] | Phase 1 | 56 participants (Actual) | Interventional | 2019-08-06 | Active, not recruiting |
| Phase II Trial of Daratumumab Retreatment in Patients With Relapsed Multiple Myeloma [NCT03841565] | Phase 2 | 0 participants (Actual) | Interventional | 2020-08-07 | Withdrawn(stopped due to There are no patients enrolled on this study and all efforts are being discontinued.) |
| A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma [NCT03567616] | Phase 2 | 8 participants (Actual) | Interventional | 2018-10-18 | Terminated(stopped due to Following results of the primary progression-free survival analysis from Study NCT02755597, company-sponsored MM studies were placed on partial clinical hold (PCH). Sponsor did not pursue release of the PCH for this study.) |
| A Single-arm, Prospective, Multicenter Clinical Trial of the Combination of Thiotepa and Pomalidomide for the Treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma. [NCT05931328] | Phase 2 | 28 participants (Anticipated) | Interventional | 2022-10-15 | Recruiting |
| A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab [NCT04302324] | Phase 2 | 40 participants (Anticipated) | Interventional | 2021-10-28 | Recruiting |
| Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Relapsed/Refractory Light Chain Amyloidosis Patients Previously Exposed to Daratumumab [NCT04270175] | Phase 2 | 21 participants (Anticipated) | Interventional | 2021-04-14 | Recruiting |
| A Multicenter Open Label Phase II Study of Pomalidomide and Cyclophosphamide and Dexamethasone in Relapse/Refractory Multiple Myeloma Patients Who Were First Treated Within the IFM/DFCI 2009 Trial [NCT02244125] | Phase 2 | 100 participants (Actual) | Interventional | 2014-04-14 | Completed |
| Hase I Open-Label Two-Part Study To Evaluate The Effect Of Food and Of CYP1A2 Induction On Pomalidomide (CC-4047) Pharmacokinetics in Healthy Subjects [NCT02168205] | Phase 1 | 55 participants (Actual) | Interventional | 2014-05-30 | Completed |
| Multiple Phase 1/2 Cohorts of Nivolumab Monotherapy or Nivolumab Combination Regimens Across Relapsed/Refractory Hematologic Malignancies [NCT01592370] | Phase 1/Phase 2 | 316 participants (Actual) | Interventional | 2012-08-02 | Active, not recruiting |
| A Phase 1b Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Anti-Tumor Activity of an Alternative Liquid Formulation of ACY-1215 (Ricolinostat) In Combination With Pomalidomide and Low-Dose Dexamethasone [NCT02189343] | Phase 1 | 16 participants (Actual) | Interventional | 2014-09-15 | Completed |
| 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 |
| Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone (Isa-KPd) for Patients With Relapsed/Refractory Multiple Myeloma [NCT04883242] | Phase 2 | 37 participants (Anticipated) | Interventional | 2021-07-29 | Recruiting |
| An Exploratory Study to Evaluate the Combination of Elotuzumab and Nivolumab With and Without Pomalidomide in Relapsed Refractory Multiple Myeloma [NCT03227432] | Phase 2 | 0 participants (Actual) | Interventional | 2018-12-31 | Withdrawn(stopped due to Withdrawn before enrollment due to issues around the FDA hold on PD-1/PD-L1 drugs in combination with IMIDs.) |
| 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 |
| A Phase II, Multicenter, Open-Label Study of the Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma [NCT05408026] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2022-10-01 | Withdrawn(stopped due to Study withdrawn, trial therapy deemed no longer novel and there was a lack of site interest.) |
| Phase II Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma A University of California Hematologic Malignancies Consortium Protocol (UCHMC1809) [NCT03590652] | Phase 2 | 46 participants (Anticipated) | Interventional | 2018-10-17 | Active, not recruiting |
| 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 |
| A Phase II Study of Daratumumab With Weekly Carfilzomib, Pomalidomide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma [NCT04176718] | Phase 2 | 43 participants (Anticipated) | Interventional | 2020-05-18 | Recruiting |
| A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide, Bortezomib and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma [NCT01734928] | Phase 3 | 559 participants (Actual) | Interventional | 2013-01-07 | Completed |
| Phase 1-2 UMBRELLA Trial Evaluating Isatuximab With or Without Dexamethasone in Combination With Novel Agents Compared to Isatuximab With Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (RRMM) - Master Protocol [NCT04643002] | Phase 1/Phase 2 | 197 participants (Anticipated) | Interventional | 2021-01-25 | 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 |
| A Pilot, Open-label, Randomized, Two-Way Crossover, Single-Dose Bioequivalence Study of Pomalidomide Under Fasting Condition in Indian Healthy Volunteers [NCT06058689] | Phase 1 | 10 participants (Anticipated) | Interventional | 2024-09-15 | Not yet recruiting |
| A Phase 2, Multicenter, Open-label, Study to Determine the Safety and Efficacy for the Combination of Durvalumab (DURVA) and Daratumumab (DARA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) [NCT02807454] | Phase 2 | 37 participants (Actual) | Interventional | 2016-07-07 | Terminated(stopped due to Health Authority request due to class effect) |
| A Pilot, Open-label, Randomized, Two-Way Crossover, Single-Dose Bioequivalence Study of Pomalidomide Under Fasting Condition in Chinese Healthy Volunteers. [NCT03424928] | Phase 1 | 12 participants (Actual) | Interventional | 2018-01-19 | Completed |
| A Phase 2 Study of Selinexor, Pomalidomide, and Dexamethasone For Multiple Myeloma With Central Nervous System Involvement [NCT05478993] | Phase 2 | 21 participants (Anticipated) | Interventional | 2022-10-12 | Recruiting |
| Personalized Selinexor-based Therapy for Relapsed/Refractory Multiple Myeloma [NCT04925193] | Phase 2 | 25 participants (Anticipated) | Interventional | 2021-11-18 | Recruiting |
| Phase I/II Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas (Primary Effusion Lymphoma and Large Cell Lymphoma Arising in KSHV-Associated Multicentric Castleman Disease) [NCT02228512] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2014-08-15 | Withdrawn |
| A Phase I Single Arm Study to Assess the Safety and Efficacy of Pomalidomide in Patients With Bleeding Due to Hereditary Hemorrhagic Telangiectasia and Refractory Angiodysplasia [NCT02287558] | Phase 1 | 9 participants (Actual) | Interventional | 2015-01-27 | Completed |
| Multicenter Non-interventional Study to Investigate Drug Utilization of Pomalidomide in Clinical Practice for the Treatment of Relapsed/Refractory Multiple Myeloma (rrMM) [NCT02555839] | | 150 participants (Anticipated) | Observational | 2015-02-20 | Active, not recruiting |
| Expanded Access for CC-4047 [NCT03723096] | | 0 participants | Expanded Access | | No longer available |
| Phase 2 Trial of Pomalidomide, Ixazomib and Dexamethasone in Patients With Multiple Myeloma With Extramedullary Disease or Plasma Cell Leukemia [NCT02547662] | Phase 2 | 17 participants (Actual) | Interventional | 2015-12-24 | Completed |
| Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day: Reduction in Costs, Same Efficacy? A PKPD Bioequivalence Pilot Study; the POMAlternative Study [NCT05555329] | Phase 4 | 12 participants (Anticipated) | Interventional | 2022-12-01 | Not yet recruiting |
| A Phase 1, Multicenter, Open-label, Dose-escalation Study in Japan to Determine the Tolerated Dose and to Evaluate the Safety, Efficacy, and Pharmacokinetics of Pomalidomide Alone or in Combination With Dexamethasone in Patients With Refractory or Relapse [NCT01568294] | Phase 1 | 12 participants (Actual) | Interventional | 2012-04-01 | Completed |
| Myeloma-Developing Regimens Using Genomics (MyDRUG) (Genomics Guided Multi-arm Trial of Targeted Agents Alone or in Combination With a Backbone Regimen) [NCT03732703] | Phase 1/Phase 2 | 228 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| Pomalidomide, Bortezomib and Dexamethasone (PVd) Versus Bortezomib and Dexamethasone (Vd) in NDMM Patients With Renal Injury (RI)：A Multicenter, Randomized Controlled, Open-label Trial. [NCT05432414] | Phase 2 | 79 participants (Anticipated) | Interventional | 2022-12-08 | Recruiting |
| A Phase 1b, Dose Escalation and Expansion Study of Lemzoparlimab With or Without Dexamethasone and in Combination With Anti-Myeloma Regimens for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma [NCT04895410] | Phase 1 | 8 participants (Actual) | Interventional | 2022-01-17 | Terminated(stopped due to Strategic considerations) |
| (INTREPID-1) A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Oprozomib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma [NCT02939183] | Phase 1 | 61 participants (Actual) | Interventional | 2017-01-17 | Completed |
| Randomized Phase 2 Study of Daunorubicin and Cytarabine Liposome + Pomalidomide Versus Daunorubicin and Cytarabine Liposome in Newly Diagnosed AML With MDS-Related Changes [NCT04802161] | Phase 2 | 78 participants (Anticipated) | Interventional | 2022-08-24 | Recruiting |
| A Phase 1b Study of SAR650984 (Isatuximab) in Combination With Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma [NCT02283775] | Phase 1 | 54 participants (Actual) | Interventional | 2015-05-15 | Completed |
| Phase I Study of Pomalidomide, Bortezomib, and Dexamethasone (PVD) as First-Line Treatment of AL Amyloidosis or Light Chain Deposition Disease [NCT01728259] | Phase 1 | 18 participants (Actual) | Interventional | 2013-03-31 | Terminated(stopped due to FDA placed the study on a clinical hold, due to the concerns by the FDA and Health Canada, Celgene decided to permanently close the study.) |
| A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma [NCT03030261] | Phase 2 | 25 participants (Actual) | Interventional | 2017-11-22 | Active, not recruiting |
| A Phase 1b Trial of Vactosertib in Combination With Pomalidomide (POM) in Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM) [NCT03143985] | Phase 1 | 18 participants (Anticipated) | Interventional | 2017-07-21 | Active, not recruiting |
| Study of Pomalidomide in Anal Cancer Precursors (SPACE): a Phase 2 Study of Immunomodulation in People With Persistent HPV-associated High Grade Squamous Intraepithelial Lesions [NCT03113942] | Phase 2 | 26 participants (Actual) | Interventional | 2017-06-14 | Active, not recruiting |
| A Phase 2 Trial of the Efficacy and Safety of Elotuzumab in Combination With Pomalidomide, Carfilzomib and Dexamethasone Among High Risk Relapsed/ Refractory Multiple Myeloma Patients [NCT03104270] | Phase 2 | 13 participants (Actual) | Interventional | 2017-03-13 | Terminated(stopped due to The study was terminated early by Funding Sponsor due to low enrollment.) |
| A Multicenter Phase II Study of Pomalidomide Monotherapy in Kaposi Sarcoma [NCT04577755] | Phase 2 | 45 participants (Anticipated) | Interventional | 2022-03-18 | Recruiting |
| A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants With Relapsed/Refractory Multi [NCT03828292] | Phase 1 | 15 participants (Actual) | Interventional | 2019-03-14 | Active, not recruiting |
| A Multi-center, Open-label, Single-arm Clinical Study of Ixazomib/Pomalidomide/Dexamethasone (IxaPD) in the Treatment of Patients With Relapsed Multiple Myeloma [NCT04989140] | Phase 4 | 60 participants (Anticipated) | Interventional | 2021-07-26 | Recruiting |
| A Phase 1, Multicenter, Open-label, Dose-Escalation Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma [NCT02103335] | Phase 1 | 38 participants (Actual) | Interventional | 2014-06-05 | Completed |
| 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, Single-Arm Study of Selinexor in Combination With Clarithromycin, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma [NCT04843579] | Phase 2 | 4 participants (Actual) | Interventional | 2021-12-29 | Terminated(stopped due to low enrollment) |
| An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab as Monotherapy and Cevostamab Plus Pomalidomide and Dexamethasone or Cevostamab Plus Daratumumab and Dexamethasone in Patients With Relapsed or [NCT04910568] | Phase 1 | 184 participants (Anticipated) | Interventional | 2021-07-26 | Recruiting |
| A Phase II Study of Pomalidomide, Daily Low Dose Oral Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma [NCT02176213] | Phase 2 | 35 participants (Actual) | Interventional | 2014-06-30 | Completed |
| A PHASE 2 CLINICAL STUDY OF POMALIDOMIDE (CC-4047) MONOTHERAPY FOR CHILDREN AND YOUNG ADULTS WITH RECURRENT OR PROGRESSIVE PRIMARY BRAIN TUMORS [NCT03257631] | Phase 2 | 53 participants (Actual) | Interventional | 2017-08-22 | Completed |
| A Phase II Trial of a Novel Proteasome/IMiD Combination, Ixazomib, Pomalidomide, and Dexamethasone in Relapsed Multiple Myeloma Patients [NCT02578121] | Phase 2 | 0 participants (Actual) | Interventional | 2015-12-31 | Withdrawn(stopped due to Investigator decided to close study without enrollment) |
| 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 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma [NCT04892446] | Phase 2 | 153 participants (Anticipated) | Interventional | 2021-11-09 | Active, not recruiting |
| A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple [NCT02990338] | Phase 3 | 307 participants (Actual) | Interventional | 2016-12-22 | Completed |
| Multi-Center Phase II Study With Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage [NCT00949364] | Phase 2 | 103 participants (Actual) | Interventional | 2009-12-31 | Completed |
| Multicenter Open Label Phase 2 Single Arm Study of Ixazomib, Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Characterized With Genomic Abnormalities of Adverse Adverse Prognostic [NCT03683277] | Phase 2 | 26 participants (Actual) | Interventional | 2019-11-03 | Terminated(stopped due to Recruitment issue, 26 patients enrolled instead of 70 initially planned) |
| Phase I/II Trial of MLN9708 Plus Pomalidomide and Dexamethasone for Relapsed or Relapsed Refractory Multiple Myeloma [NCT02119468] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2014-06-30 | Active, not recruiting |
| A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma [NCT03170882] | Phase 2 | 122 participants (Actual) | Interventional | 2017-08-01 | Completed |
| Belantamab Mafodotin in Combination With Nirogacestat and Pomalidomide in Patients With Relapsed or Refractory Multiple Myeloma [NCT05556798] | Phase 1 | 30 participants (Anticipated) | Interventional | 2022-10-04 | Recruiting |
| Pilot Study (Phase II) of Pomalidomide, Oral Dexamethasone and Very Low-dose Cyclophosphamide in Patients With Refractory Multiple Myeloma Who Have Received Lenalidomide and Bortezomib [NCT04243109] | Phase 2 | 6 participants (Actual) | Interventional | 2017-02-23 | Terminated(stopped due to Low recruitment rate. Lack of interest of the sponsor.) |
| A Phase 3, Multicenter, Randomized, Open Label Study of ABBV-383 Compared With Standard Available Therapies in Subjects With Relapsed or Refractory Multiple Myeloma (3L+ RRMM Monotherapy Study) [NCT06158841] | Phase 3 | 380 participants (Anticipated) | Interventional | 2024-04-26 | Not yet recruiting |
| A Prospective, Non-interventional, Multinational, Observational Study With Isatuximab in Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM) [NCT04458831] | | 1,200 participants (Anticipated) | Observational [Patient Registry] | 2020-08-13 | Recruiting |
| Prospective Follow-up of Relapse Myeloma Patients After Previous Exposure to Bortezomib and Lenalidomide Treated on Pomalidomide and Dexamethasone [NCT02158702] | Phase 2 | 100 participants (Anticipated) | Interventional | 2014-11-30 | Active, not recruiting |
| Clinical Study of Efficacy and Safety of Novel Targeted Drugs Combined With R-ICE Regimen in the Treatment of Relapsed and Refractory Diffuse Large B-cell Lymphoma [NCT05348213] | Phase 2 | 76 participants (Anticipated) | Interventional | 2022-05-16 | Recruiting |
| 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 2 Study of Isatuximab in Combination With Pomalidomide and Dexamethasone in MM Patients Who Received One Prior Line of Therapy Containing Lenalidomide and a Proteasome Inhibitor [NCT05298683] | Phase 2 | 108 participants (Anticipated) | Interventional | 2022-05-31 | Not yet recruiting |
| A Phase 2, Multicenter, Open-label, Single Arm, Two-stage Study to Evaluate the Efficacy and Safety of CC-4047 (Pomalidomide) in Patients With Advanced Soft Tissue Sarcomas Who Have Relapsed or Are Refractory to Systemic Anticancer Therapy [NCT00717522] | Phase 2 | 7 participants (Actual) | Interventional | 2008-08-01 | Terminated(stopped due to Study enrollment was terminated due to a corporate strategic decision unrelated to patient safety.) |
| Phase Ib of Cyclophosphamide, Pomalidomide, Dexamethasone and Daratumumab (CPD-DARA) in Patients With Relapsed/Refractory Multiple Myeloma. (The CPD-DARA Study) [NCT04667663] | Phase 1 | 20 participants (Anticipated) | Interventional | 2021-12-08 | Active, not recruiting |
| Phase I Study of Pomalidomide, Dexamethasone and Rituximab (PDR) in Relapsed or Refractory Waldenstrom's Macroglobulinemia [NCT01078974] | Phase 1 | 7 participants (Actual) | Interventional | 2010-05-31 | Terminated(stopped due to Safety concerns (IgM Flare)) |
| A Phase II Study of Dexamethasone (DECADRON®), Clarithromycin (BIAXIN®), and Pomalidomide (CC-4047®) for Subjects With Relapsed or Refractory Multiple Myeloma [NCT01159574] | Phase 2 | 121 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A Single-arm, Multisite, Prospective Study of Ixazomib-pomalidomide-dexamethasone as Second or Third-line Combination Treatment for Patients With Relapsed and Refractory Multiple Myeloma (RRMM) Previously Treated With Daratumumab, Lenalidomide and Bortezo [NCT04790474] | Phase 2 | 60 participants (Anticipated) | Interventional | 2021-03-25 | Recruiting |
| A Phase 2 Study With Safety Run-In of Marizomib, Pomalidomide, and Dexamethasone For Relapsed and Refractory Multiple Myeloma and CNS Myeloma [NCT05050305] | Phase 2 | 30 participants (Anticipated) | Interventional | 2024-03-31 | Not yet recruiting |
| 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 Clinical Trial for Evaluation of Nivolumab and Pomalidomide Combination for Relapsed/Refractory Primary Central Nervous System Lymphoma and Primary Vitreoretinal Lymphoma [NCT03798314] | Phase 1 | 3 participants (Actual) | Interventional | 2019-01-30 | Completed |
| A Multicenter Randomized Open Label Phase II Study of Pomalidomide and Dexamethasone in Relapse and Refractory Multiple Myeloma Patients Who Are Progressive and Did Not Achieve at Least a Partial Response to Bortezomib and Lenalidomide [NCT01053949] | Phase 2 | 84 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Phase I Trial of Pomalidomide for Children With Recurrent, Progressive, or Refractory CNS Tumors [NCT02415153] | Phase 1 | 29 participants (Actual) | Interventional | 2015-07-14 | Completed |
| Maintenance Therapy With Carfilzomib, Pomalidomide and Dexamethasone (CPd) in High-Risk Myeloma Patients: A Phase 2 Study With a Safety Run-In [NCT03756896] | Phase 2 | 29 participants (Actual) | Interventional | 2019-01-25 | Active, not recruiting |
| A Phase 2 Multicenter, Open-label Study to Determine the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Moderate or Severe Renal Impairment Including Su [NCT02045017] | Phase 2 | 81 participants (Actual) | Interventional | 2014-02-28 | Completed |
| Phase II Multicenter, Open-label, Single Arm Clinical Study of Pomalidomide and dexamethasonE in RelapSed Myeloma Plus rEsponse Adapted Cyclophosphamide as a Tailored InnoVativE Strategy [NCT02046915] | Phase 2 | 60 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Phase 2, Open-Label, Single-Arm, Pilot Study of Safety and Efficacy of CC-4047 (Pomalidomide) in Patients With Advanced Chronic Graft-Versus-Host Disease Developing After Allogeneic Hematological Stem Cell Transplantation [NCT00770757] | Phase 2 | 13 participants (Actual) | Interventional | 2009-02-28 | Completed |
| An Open-Label, Randomized Phase 3 Trial of Combinations of Nivolumab, Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma [NCT02726581] | Phase 3 | 170 participants (Actual) | Interventional | 2016-08-10 | Completed |
| A Phase 2, Prospective, Randomized, Multicenter, Double-blind, Active-control, Parallel-group Study to Determine the Safety of and to Select a Treatment Regimen of CC-4047 (Pomalidomide) Either as Single-agent or in Combination With Prednisone to Study Fu [NCT00463385] | Phase 2 | 88 participants (Actual) | Interventional | 2007-04-01 | Completed |
| A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide Plus Lowdose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 3) [NCT04162210] | Phase 3 | 325 participants (Actual) | Interventional | 2020-04-02 | Active, not recruiting |
| A Phase 3, Two-Stage, Randomized, Multicenter, Open-Label Study Comparing Mezigdomide (CC-92480), Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Subjects With Relapsed or Refractory Multiple Myeloma (RRMM) [NCT05519085] | Phase 3 | 810 participants (Anticipated) | Interventional | 2022-09-20 | Recruiting |
| AN OPEN-LABEL, 3-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) MONOTHERAPY AND ELRANATAMAB + DARATUMUMAB VERSUS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE IN PARTICIPANTS WITH RELAPSED/REFRACTO [NCT05020236] | Phase 3 | 764 participants (Anticipated) | Interventional | 2021-10-04 | Recruiting |
| A Phase 1, Double-blind, Four Period Crossover Study to Investigate the Effects of Pomalidomide (CC 4047) on the QT Interval in Healthy Male Subjects [NCT01986894] | Phase 1 | 72 participants (Actual) | Interventional | 2013-10-18 | Completed |
| Phase II Study of Immunomaintenance Using POmalidomide With Elotuzumab afteR Second Autologous Transplant (Immuno-POWER Trial): Big Ten Cancer Research Consortium BTCRC-MM19-428 [NCT04584307] | Phase 2 | 0 participants (Actual) | Interventional | 2021-04-30 | Withdrawn(stopped due to Funder pulled support/funding) |
| A MULTICENTER, OPEN LABEL PHASE I/II STUDY OF CARFILZOMIB, POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (MM) PATIENTS [NCT02185820] | Phase 1/Phase 2 | 57 participants (Actual) | Interventional | 2014-06-30 | Completed |
| Autologous Stem Cell Transplant With Pomalidomide (CC-4047®) Maintenance Versus Continuous Clarithromycin/ Pomalidomide / Dexamethasone Salvage Therapy in Relapsed or Refractory Multiple Myeloma: A Phase 2 Open-Label Randomized Study by Tristate Consortiu [NCT01745588] | Phase 2 | 23 participants (Actual) | Interventional | 2012-12-31 | Active, not recruiting |
| A Phase I Study of Pomalidomide Given at the Time of Lymphocyte Recovery Following Induction Timed Sequential Chemotherapy With Cytarabine, Daunorubicin and Etoposide (AcDVP16) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk MD [NCT02029950] | Phase 1 | 50 participants (Actual) | Interventional | 2013-12-16 | Completed |
| Phase I Trial of Pomalidomide and Dose-Adjusted EPOCH +/- Rituximab for HIV-Associated Lymphomas [NCT05389423] | Phase 1 | 20 participants (Anticipated) | Interventional | 2023-06-27 | Recruiting |
| Phase 2 Trial of Induction With Ixazomib, Pomalidomide, Dexamethasone Prior to Salvage Autologous Stem Cell Transplant Followed by Consolidation With Ixazomib, Pomalidomide, and Dexamethasone and Ixazomib Maintenance in Multiple Myeloma [NCT03202628] | Phase 2 | 8 participants (Actual) | Interventional | 2017-07-24 | Completed |
| A Phase I Study of Pomalidomide and Nivolumab in Patients With Virus-Associated Malignancies With or Without HIV [NCT04902443] | Phase 1 | 54 participants (Anticipated) | Interventional | 2021-12-10 | Recruiting |
| A Phase 1/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 Monotherapy, or in Combination With Pomalidomide, With and Without Dexamethasone in Subjects With Relapsed or Refractory Multiple [NCT03287908] | Phase 1 | 174 participants (Actual) | Interventional | 2017-11-13 | Terminated(stopped due to business decision, not safety reasons.) |
| A Phase 1a/1b Multicenter, Single-Arm, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relap [NCT02400242] | Phase 1 | 85 participants (Actual) | Interventional | 2015-05-07 | Active, not recruiting |
| A Phase 1 Trial of Pomalidomide in Combination With Liposomal Doxorubicin in Patients With Advanced or Refractory Kaposi Sarcoma [NCT02659930] | Phase 1 | 99 participants (Anticipated) | Interventional | 2016-01-13 | Recruiting |
| Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003 [NCT01324947] | Phase 3 | 74 participants (Actual) | Interventional | 2011-03-01 | Completed |
| A Phase 1b Trial of AR-42 With Pomalidomide in Relapsed Multiple Myeloma [NCT02569320] | Phase 1 | 9 participants (Actual) | Interventional | 2016-05-20 | Completed |
| Phase 1/2 Trial of Selinexor in Combination With Pomalidomide and Dexamethasone ± Carfilzomib for Patients With Proteasome-Inhibitor and Immunomodulatory Drug Refractory Multiple Myeloma (SCOPE) [NCT04764942] | Phase 1/Phase 2 | 81 participants (Anticipated) | Interventional | 2021-05-06 | Recruiting |
| A Phase I/II Multicenter, Randomized, Open Label, Dose-Escalation Study To Determine The Maximum Tolerated Dose, Safety, And Efficacy Of CC-4047 Alone Or In Combination With Low-Dose Dexamethasone In Patients Wth Relapsed And Refractory Multiple Myeloma W [NCT00833833] | Phase 1/Phase 2 | 259 participants (Actual) | Interventional | 2008-06-30 | Completed |
| Zn-DDC to Target Hypoxia-NFkappaB-CSCs Pathway and Improve the Treatment Outcomes of Haematological Malignancies - A Translation Bench Study [NCT04234022] | | 70 participants (Anticipated) | Observational | 2021-10-22 | Recruiting |
| A Phase 2 Study of Pomalidomide as a Replacement for Lenalidomide for Multiple Myeloma Patients Relapsed or Refractory to a Lenalidomide-Containing Combination Regimen [NCT02188368] | Phase 2 | 45 participants (Actual) | Interventional | 2014-07-07 | Terminated(stopped due to Lack of enrollment) |
| Phase I/II Study of Ixazomib in Combination With Pomalidomide, Clarithromycin and Dexamethasone (PiC-D) in Patients With Double Refractory Multiple Myeloma [NCT02542657] | Phase 1/Phase 2 | 30 participants (Actual) | Interventional | 2015-10-31 | Active, not recruiting |
| Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China [NCT04762745] | Phase 1/Phase 2 | 56 participants (Anticipated) | Interventional | 2021-02-28 | Not yet recruiting |
| 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 Multicenter, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone in Chinese Patients With Relapsed and Refractory Multiple Myeloma [NCT02916420] | Phase 3 | 73 participants (Anticipated) | Interventional | 2016-09-30 | Recruiting |
| Study of Isatuximab Plus Pomalidomide and Dexamethasone in Highly Toxicity-vulnerable Subjects With Relapsed or Refractory Multiple Myeloma [NCT05911321] | Phase 2 | 49 participants (Anticipated) | Interventional | 2023-12-30 | Not yet recruiting |
| Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma [NCT01889420] | Phase 1 | 1 participants (Actual) | Interventional | 2014-07-31 | Terminated(stopped due to Low accrual) |
| A Phase 1, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Pomalidomide (CC-4047) Following Multiple Daily Doses in Healthy Male Subjects [NCT01474330] | Phase 1 | 33 participants (Actual) | Interventional | 2011-08-01 | Completed |
| Phase II Randomized Open-Label, Two-Arm Study of Safety and Efficacy of CC-4047 in Subjects With Metastatic Hormone Refractory Prostate Cancer (HRPC) [NCT00072722] | Phase 2 | 36 participants | Interventional | 2003-09-30 | Completed |
| A Phase 2, Multicenter, Multi-cohort, Open-label Study of Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following [NCT01946477] | Phase 2 | 186 participants (Actual) | Interventional | 2014-05-29 | Active, not recruiting |
| A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male Subjects [NCT01707407] | Phase 1 | 32 participants (Actual) | Interventional | 2012-09-01 | Completed |
| A Phase I, Open-Label Study to Determine the Maximum Tolerated Dose (MTD) and to Evaluate the Safety Profile of CC-4047 in Subjects With Advanced Solid Tumors [NCT00482521] | Phase 1 | 42 participants (Actual) | Interventional | 2007-03-31 | 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 |
| 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 |
| A Phase II Multicenter Study of Pomalidomide Monotherapy in HIV-Positive Individuals With Kaposi Sarcoma (KS) in Sub-Saharan Africa (SSA) [NCT03601806] | Phase 2 | 26 participants (Actual) | Interventional | 2021-04-26 | Active, not recruiting |
| A Randomized Phase 2 Single-Center Study of Pomalidomide for Chronic GvHD [NCT01688466] | Phase 2 | 34 participants (Actual) | Interventional | 2012-08-30 | Completed |
| Pomalidomide in Relapsed and Refractory Multiple Myeloma (RRMM) [NCT02406222] | Phase 2 | 124 participants (Actual) | Interventional | 2016-03-31 | Active, not recruiting |
| Prospective Exploratory Clinical Study of Orelabrutinib, Pomalidomide, Rituximab Combined With miniCHOP-like Regimen in Treatment-naive Elderly Patients With DLBCL [NCT05809180] | | 35 participants (Anticipated) | Interventional | 2023-01-04 | Recruiting |
| A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With R [NCT04484623] | Phase 3 | 357 participants (Anticipated) | Interventional | 2020-10-01 | Recruiting |
| Phase II Trial of Sequential Treatment of Multiple Myeloma With Antibody Therapy [NCT03713294] | Phase 2 | 41 participants (Anticipated) | Interventional | 2018-12-19 | Active, not recruiting |
| A Prospective, Multi-Center, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety and Effect on Induction of Fetal Hemoglobin of CC-4047 In Subjects With Sickle Cell Disease [NCT01522547] | Phase 1 | 12 participants (Anticipated) | Interventional | 2007-08-01 | Completed |
| A Phase 1/2 Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, A Hypoxia-Activated Prodrug, and Dexamethasone With or Without Bortezomib or Pomalidomide in Subjects With Relapsed/Refractory Multiple Myeloma [NCT01522872] | Phase 1/Phase 2 | 98 participants (Anticipated) | Interventional | 2012-02-29 | Active, not recruiting |
| 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)) |
| A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients With Relapsed/Refractory Multiple Myeloma [NCT01541332] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2012-02-29 | Active, not recruiting |
| A Phase I/II Assessment of Combination Immuno-Oncology Drugs Elotuzumab, Anti-LAG-3 (BMS-986016) and Anti-TIGIT (BMS-986207) [NCT04150965] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2020-06-30 | Active, not recruiting |
| A Phase I/II Clinical Trial of Pomalidomide With Melphalan and Dexamethasone in Patients With Newly Diagnosed Untreated Systemic AL Amyloidosis: Trial Stopped During Phase I [NCT01807286] | Phase 1 | 3 participants (Actual) | Interventional | 2014-01-31 | Terminated(stopped due to Sponsor requested termination) |
| A Non-interventional Post Authorisation Registry of Patients Treated With Pomalidomide for Relapsed and Refractory Multiple Myeloma Who Have Received at Least Two Prior Treatment Regimens, Including Both Lenalidomide and Bortezomib, and Have Demonstrated [NCT02164955] | | 775 participants (Actual) | Observational [Patient Registry] | 2014-06-26 | Completed |
| A Phase I/II Study of CC-4047 in Combination With Gemcitabine in Subjects With Untreated Advanced Carcinoma of the Pancreas [NCT00540579] | Phase 1/Phase 2 | 23 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Pomalidomide, Ixazomib, and Dexamethasone (PId) With or Without Intensification by Cyclophosphamide (PICd): A Phase II Study in Relapsed or Refractory Multiple Myeloma [NCT03731832] | Phase 2 | 82 participants (Anticipated) | Interventional | 2018-09-20 | Active, not recruiting |
| A Multicenter, Phase I/IIA, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose and To Evaluate the Safety Profile of CC-4047 Administered in Combination With Cisplatin and Etoposide in Patients With Extensive Disease Small Cell Lung [NCT00537511] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2008-02-01 | Terminated(stopped due to This study was terminated for administrative reasons.) |
| Phase I Study of Pomalidomide in Relapsed or Refractory Waldenstrom Macroglobulinemia [NCT01198067] | Phase 1 | 15 participants (Actual) | Interventional | 2010-10-06 | Active, not recruiting |
| A Multicenter, Open-Label, Single-Arm Clinical Study of the Efficacy and Safety of Pomalidomide Capsules Combined With Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma [NCT05236621] | Phase 3 | 85 participants (Actual) | Interventional | 2021-01-04 | 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 |
| 1454GCC: Phase I/II Anti-PD-1 (MK-3475) and IMiD (Pomalidomide) Combination Immunotherapy in Relapsed/Refractory Multiple Myeloma [NCT02289222] | Phase 1/Phase 2 | 48 participants (Actual) | Interventional | 2014-12-30 | Terminated(stopped due to Due to the inclusion of an IMid in combination with pembrolizumab, Study Sponsor terminated the study.) |
| Post Marketing Surveillance on Safety Evaluation of POMALYST® (Pomalidomide) Treatment of Multiple Myeloma in Korea [NCT03288974] | | 600 participants (Anticipated) | Observational | 2017-12-28 | Recruiting |
| A Phase 1, Multicenter, Open Label, Dose-escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide (POM), Bortezomib (BTZ) and Low-Dose Dexamethasone (LDDEX) in Subjects With Relapsed or Refractory Multiple Myeloma (MM) [NCT01497093] | Phase 1 | 34 participants (Actual) | Interventional | 2012-02-15 | Completed |
| An Open-label, Phase II Study of Pomalidomide and Dexamethasone (PDex) for Previously Treated Patients With AL Amyloidosis. [NCT01510613] | Phase 2 | 28 participants (Actual) | Interventional | 2012-02-29 | Completed |
| A Multicenter, Single-Arm, Open-Label Treatment Use Protocol for Pomalidomide (POM) in Combination With Low Dose Dexamethasone (LD-Dex) in Patients With Relapsed or Refractory Multiple Myeloma [NCT01632826] | | 0 participants | Expanded Access | | Approved for marketing |
| A Phase 1/2a Open-label, Dose-Escalation Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-079 Administered Subcutaneously as a Single Agent in Patients With Relapsed/Refractory Multiple Myeloma [NCT03439280] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2018-04-20 | Completed |
| A Multicenter Open Label Phase II Study of Pomalidomide and Dexamethasone in Progressive Relapsed or Refractory Multiple Myeloma Patients With Deletion 17p or Translocation (4;14) Adverse Karyotypic Abnormalities-IFM2010-02 [NCT01745640] | Phase 2 | 63 participants (Actual) | Interventional | 2012-01-31 | Completed |
| 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 |
| Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial [NCT03520985] | Phase 2 | 34 participants (Actual) | Interventional | 2018-10-01 | Terminated(stopped due to Feasibility (low patient accrual and financial reasons)) |
| Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed/or Refractory Multiple Myeloma [NCT04094961] | Phase 1/Phase 2 | 61 participants (Anticipated) | Interventional | 2019-09-18 | Recruiting |
| A Phase I-II Study of the Combination of Bendamustine and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01754402] | Phase 1/Phase 2 | 56 participants (Actual) | Interventional | 2013-01-07 | Active, not recruiting |
| 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 II Trial of CC-4047 Plus Dexamethasone in Patients With Relapsed of Refractory Multiple Myeloma or Amyloidosis [NCT00558896] | Phase 2 | 378 participants (Actual) | Interventional | 2007-11-30 | Completed |
| A Phase 2, Open Label, Multicenter, Single-stage Study to Evaluate the Efficacy of Isatuximab Plus Pomalidomide and Dexamethasone (IPd), in Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy [NCT05066607] | Phase 2 | 46 participants (Anticipated) | Interventional | 2022-02-11 | 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 II Study of Belantamab Mafodotin in Combination With Carfilzomib, Pomalidomide, and Dexamethasone (KPd) in Patients With Relapsed Multiple Myeloma [NCT05789303] | Phase 2 | 83 participants (Anticipated) | Interventional | 2023-05-30 | Recruiting |
| [NCT03023527] | Phase 1 | 6 participants (Actual) | Interventional | 2017-01-31 | Terminated(stopped due to Safety) |
| A Phase 1 Multi-Center, Open-Label, Dose-Escalation Study to Determine the Pharmacokinetics and Safety of Pomalidomide When Given in Combination With Low Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma and Impaired Renal Functi [NCT01575925] | Phase 1 | 25 participants (Actual) | Interventional | 2012-06-01 | Completed |
| A Phase I Study of INCB053914 (Pan-PIM Kinase Inhibitor) and Pomalidomide With Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma [NCT04355039] | Phase 1 | 0 participants (Actual) | Interventional | 2021-07-01 | Withdrawn(stopped due to Terminated for lack of funding.) |
| Phase II Trial of Pomalidomide in GEP-defined High-risk Multiple Myeloma That is Relapsing or Refractory to Prior Therapy [NCT01177735] | Phase 2 | 71 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase-3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Compare Efficacy and Safety of Pomalidomide in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis and Red Blood Cell-Transfusion-Dependence [NCT01178281] | Phase 3 | 267 participants (Actual) | Interventional | 2010-09-08 | Completed |
| Phase II, Single-arm Trial of Carfilzomib, Pomalidomide, and Dexamethasone for Myeloma Patients Who Had Relapsed or Progressed After Carfilzomib, Lenalidomide, and Dexamethasone [NCT05509374] | Phase 2 | 33 participants (Anticipated) | Interventional | 2021-10-28 | Recruiting |
| Maintenance Therapy With Belantamab, Pomalidomide and Dexamethasone (BPd) in High-Risk Myeloma Patients: A Phase 2 Study With a Safety Run-In [NCT05208307] | Phase 2 | 34 participants (Anticipated) | Interventional | 2022-07-21 | Recruiting |
| A Randomized Multicenter Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma [NCT02548962] | Phase 1/Phase 2 | 11 participants (Actual) | Interventional | 2016-03-31 | Terminated(stopped due to After completing Phase 1, the Sponsor elected not to move forward with Phase 2.) |
| A Phase 3, Open-Label Study of Elranatamab Monotherapy Versus Elotuzumab, Pomalidomide, Dexamethasone (EPd) Or Pomalidomide, Bortezomib, Dexamethasone (PVd) Or Carfilzomib, Dexamethasone (Kd) In Participants With Relapsed/Refractory Multiple Myeloma Who R [NCT06152575] | Phase 3 | 492 participants (Anticipated) | Interventional | 2023-12-18 | Not yet recruiting |
| A Phase-Ib/II Study of Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary Myelofibrosis [NCT01644110] | Phase 1/Phase 2 | 96 participants (Actual) | Interventional | 2013-08-31 | Active, not recruiting |
| Daratumumab, Pomalidomide and Dexamethasone for Del(17p) Positive Relapsed and Relapsed/Refractory Multiple Myeloma Patients [DEDALO] [NCT04124497] | Phase 2 | 45 participants (Anticipated) | Interventional | 2019-07-01 | Active, not recruiting |
| A Phase 3, Muticenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone Versus High-dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma [NCT01311687] | Phase 3 | 455 participants (Actual) | Interventional | 2011-03-11 | Completed |
| Phase I/II, Multicenter, Open Label, Clinical Trial of Filanesib (ARRY-520) in Combination With Pomalidomide and Dexamethasone for Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients [NCT02384083] | Phase 1/Phase 2 | 47 participants (Actual) | Interventional | 2015-09-30 | Completed |
| 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.) |
| A Phase 2, Multiple Cohort Study of Elotuzumab in Combination With Pomalidomide and Low-Dose Dexamethasone (EPd), and in Combination With Nivolumab (EN), in Patients With Multiple Myeloma Relapsed or Refractory to Prior Treatment With Lenalidomide. [NCT02612779] | Phase 2 | 74 participants (Actual) | Interventional | 2016-02-09 | Completed |
| A Phase III Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (KEYNOTE 183) [NCT02576977] | Phase 3 | 251 participants (Actual) | Interventional | 2015-10-19 | Terminated(stopped due to The study was terminated early due to business reasons) |
| A Phase 1, Open-Label, Two-Part Study to Evaluate the Pharmacokinetics of Pomalidomide (CC-4047) in Hepatically Impaired Male Subjects [NCT01835561] | Phase 1 | 32 participants (Actual) | Interventional | 2013-03-01 | Completed |
| Phase I Trial of Pomalidomide for Patients With Relapsed/Refractory Primary CNS Lymphoma and Primary Vitreoretinal Lymphoma [NCT01722305] | Phase 1 | 29 participants (Actual) | Interventional | 2013-04-08 | Completed |
| A Multisite, Phase II Study of Isatuximab, Pomalidomide, Elotuzumab and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma [NCT04835129] | Phase 2 | 53 participants (Anticipated) | Interventional | 2022-01-10 | Recruiting |
| Phase II Expansion Cohorts Studies of a Novel Triple Combination Therapy, DTRM-555, in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Non-Hodgkin's Lymphomas [NCT04305444] | Phase 2 | 120 participants (Anticipated) | Interventional | 2020-04-24 | Recruiting |
| A Phase 1 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of Intravenous TAK-573 as Part of Combination Therapy in Patients With Relapsed or Refractory Multiple Myeloma [NCT04392648] | Phase 1 | 0 participants (Actual) | Interventional | 2020-06-24 | Withdrawn(stopped due to Business Decision (no enrollment)) |
| MC1082: A Phase I/II Trial of Pomalidomide (CC-4047), Bortezomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01212952] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A Phase I/II Study of Pomalidomide, Dexamethasone and Ixazomib vs. Pomalidomide and Dexamethasone for Patients With Multiple Myeloma Relapsing on Lenalidomide as Part of First Line Therapy [NCT02004275] | Phase 1/Phase 2 | 118 participants (Actual) | Interventional | 2014-02-28 | Active, not recruiting |
| A Phase 2, Proof-Of-Concept, Multicenter, Randomized, Double-Blind, Placebo- Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) in Subjects With Systemic Sclerosis With Interst [NCT01559129] | Phase 2 | 23 participants (Actual) | Interventional | 2012-08-09 | Terminated(stopped due to Enrollment was stopped early (see limitations and caveats section).) |
| A Phase 2, Multicenter, Single-arm, Open-label Study in Japan to Evaluate the Efficacy and Safety of Pomalidomide (CC-4047) in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma [NCT02011113] | Phase 2 | 36 participants (Actual) | Interventional | 2013-12-31 | Completed |
| Phase 1b/3 Multicenter Study of Oprozomib, Pomalidomide, and Dexamethasone in Primary Refractory or Relapsed and Refractory Multiple Myeloma Subjects [NCT01999335] | Phase 1 | 33 participants (Actual) | Interventional | 2014-07-30 | 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 OPZ007 was halted during dose-expansion.) |
| An Open-label, Randomized, Phase 3 Study of Linvoseltamab (REGN5458; Anti- BCMA x Anti-CD3 Bispecific Antibody) Versus the Combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), in Patients With Relapsed/Refractory Multiple Myeloma (LINKER-MM3) [NCT05730036] | Phase 3 | 286 participants (Anticipated) | Interventional | 2023-09-18 | Recruiting |
| A Randomized, Phase 3, Open Label Study Evaluating Subcutaneous Versus Intravenous Administration of Isatuximab in Combination With Pomalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM) [NCT05405166] | Phase 3 | 534 participants (Anticipated) | Interventional | 2022-06-23 | Recruiting |
| A Phase I/II Study of Pomalidomide (CC-4047®), Dexamethasone and Romidepsin in Patients With Relapsed or Refractory Multiple Myeloma (Romi Poma) [NCT01979276] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2013-11-30 | Terminated(stopped due to this study was terminated due to losing financial support, and enrollment challenges) |
| A Phase 2b, Open-label Study of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma (MM), Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory MM, and Selinexor and P [NCT04414475] | Phase 2 | 141 participants (Anticipated) | Interventional | 2020-07-01 | Recruiting |
| A Phase 1/2 Multi-Center, Open Label, Dose Escalation Study to Determine the RP2D, Safety and Efficacy of GSK2857916 in Combination With Pomalidomide and Low-Dose Dexamethasone in Subjects With Relapsed and/or Refractory Multiple Myeloma [NCT03715478] | Phase 1/Phase 2 | 120 participants (Anticipated) | Interventional | 2018-11-26 | 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 |
| A Phase II Study of ISABELA: Isatuximab, Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma [NCT05922501] | Phase 2 | 50 participants (Anticipated) | Interventional | 2023-11-30 | Not yet recruiting |
| A Randomized, Controlled, Open-label, Phase 3 Study of Melflufen/Dexamethasone Compared With Pomalidomide/Dexamethasone for Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Lenalidomide [NCT03151811] | Phase 3 | 495 participants (Actual) | Interventional | 2017-06-12 | Completed |
| A Phase I/II, Multi-center, Open Label Study of Pomalidomide, Cyclophosphamide and Prednisone (PCP) in Patients With Multiple Myeloma Relapsed and/or Refractory to Lenalidomide [NCT01166113] | Phase 1/Phase 2 | 67 participants (Actual) | Interventional | 2010-07-31 | Completed |
| 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 |
| A Phase 1B/2 Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of ACY-1215 (RICOLINOSTAT) in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed and Refractory Mult [NCT01997840] | Phase 1/Phase 2 | 103 participants (Actual) | Interventional | 2014-03-01 | Active, not recruiting |
| A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis [NCT01570387] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2012-06-30 | Completed |
| A Multicenter, Phase 1/1b, Open-Label, Dose-Escalation Study of ABBV-838, an Antibody Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma [NCT02462525] | Phase 1 | 74 participants (Actual) | Interventional | 2015-05-06 | Terminated(stopped due to No Go decision for ABBV-838) |
| A Phase II Study of Elotuzumab in Combination With Pomalidomide, Bortezomib, and Dexamethasone in Relapsed and Refractory Multiple Myeloma [NCT02718833] | Phase 2 | 52 participants (Actual) | Interventional | 2016-06-30 | Active, not recruiting |
| Selinexor in Combination With Immunomodulator to Treat Relapsed/Refractory Multiple Myeloma Patients [NCT04941937] | Phase 2 | 90 participants (Anticipated) | Interventional | 2022-01-27 | Recruiting |
| A Phase IB Multicenter, Open-label Study To Determine The Recommended Dose And Regimen Of Durvalumab (MEDI4736) Either As Monotherapy or In Combination With Pomalidomide (POM) With Or Without Low-Dose Dexamethasone (DEX) In Subjects With Relapsed And Refr [NCT02616640] | Phase 1 | 114 participants (Actual) | Interventional | 2016-01-11 | Active, not recruiting |
| A Phase I/II Study of Pomalidomide and Dexamethasone With Growth Factor Support in Patients With Relapsed/Refractory Multiple Myeloma [NCT01946152] | Phase 1/Phase 2 | 21 participants (Actual) | Interventional | 2014-03-05 | Terminated(stopped due to Per PI at time of CR) |
| A Multi-Center Phase I/II, Open-Label, Dose-Finding Pilot Study of the Combination of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma [NCT01464034] | Phase 1/Phase 2 | 136 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to Lack of enrollment) |
| A Phase 1/2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed/ Refractory Multiple Myeloma Pre [NCT05581875] | Phase 1/Phase 2 | 48 participants (Anticipated) | Interventional | 2022-10-20 | Not yet recruiting |
| A Phase II, Prospective, Open Label Study (PO-MMM-PI-0011) to Determine the Safety and Efficacy of Pomalidomide (CC-4047) in Subjects With Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis (PMF; Post-PV MF, or Post-ET MF) [NCT00946270] | Phase 2 | 70 participants (Actual) | Interventional | 2009-07-22 | 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 |
| An Open-label Phase I/IIa Study to Evaluate the Safety and Efficacy of CCS1477 as Monotherapy and in Combination in Patients With Advanced Haematological Malignancies. [NCT04068597] | Phase 1/Phase 2 | 250 participants (Anticipated) | Interventional | 2019-08-09 | Recruiting |
| 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 3 Randomized, Open-label Trial of Selinexor, Pomalidomide, and Dexamethasone (SPd) Versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM) [NCT05028348] | Phase 3 | 222 participants (Anticipated) | Interventional | 2022-04-19 | Recruiting |
| A Phase I/II, Prospective, Open-Label Study to Determine the Safety and Efficacy of CC-4047 in Patients With Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis® [NCT00669578] | Phase 1/Phase 2 | 77 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Evaluation of Pomalidomide in Combination With High Dose Dexamethasone and Oral Cyclophosphamide in Patients With Relapsed and Refractory Myeloma [NCT01432600] | Phase 1/Phase 2 | 80 participants (Actual) | Interventional | 2011-11-30 | Completed |
| 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.) |
| A Phase 3, Multicenter, Randomized, Open Label Study of Venetoclax and Dexamethasone Compared With Pomalidomide and Dexamethasone in Subjects With t(11;14)-Positive Relapsed or Refractory Multiple Myeloma [NCT03539744] | Phase 3 | 244 participants (Anticipated) | Interventional | 2018-10-22 | Recruiting |
| The Safety and Efficacy of Pomalidomide in Combination With Cyclophosphamide and Dexamethasone (PCD) in the Transplant-ineligible Patients With Relapsed and/or Refractory Multiple Myeloma (MM) Who Had Lenalidomide Plus Dexamethasone (LD) Following Frontli [NCT03242460] | Phase 2 | 55 participants (Actual) | Interventional | 2015-05-12 | Completed |
| Sequential Treatment Regimens With RO-MTX After Pomalidomide, Orelabrutinib, Rituximab (POR) as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial [NCT05390749] | Phase 2 | 50 participants (Anticipated) | Interventional | 2022-04-11 | Recruiting |
| Multicenter Open Label Phase 2 Study of Isatuximab Plus Pomalidomide and Dexamethasone With Carfilzomib in Relapsed or Refractory Multiple Myeloma [NCT04287855] | Phase 2 | 82 participants (Actual) | Interventional | 2020-08-28 | Active, not recruiting |
| An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd) [NCT04191616] | Phase 2 | 54 participants (Actual) | Interventional | 2020-08-06 | Active, not 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 |
| Pomalidomide for the Treatment of Bleeding in Hereditary Hemorrhagic Telangiectasia [NCT03910244] | Phase 2 | 145 participants (Actual) | Interventional | 2019-10-17 | Completed |
| Safety and Efficacy of Pomalidomide in the Treatment of Refractory Cough in Patients With Idiopathic Pulmonary Fibrosis (IPF): A Pilot Study [NCT01135199] | Phase 2 | 0 participants (Actual) | Interventional | 2010-04-30 | Withdrawn(stopped due to FDA did not accept sponsor's animal toxicology data to support proposed dosing.) |
| Clinical Research of Pomalidomide Maintenance Therapy for Primary Multiple Myeloma [NCT05378971] | | 15 participants (Anticipated) | Interventional | 2022-05-15 | Recruiting |
| A Multi-center Open Label Phase II Study of Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis. [NCT04895917] | Phase 2 | 40 participants (Anticipated) | Interventional | 2021-06-23 | Recruiting |
| 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 |
|---|
| NCT00463385 (10) [back to overview] | Change From Baseline in Hemoglobin Concentration for Non-Responders |
| NCT00463385 (10) [back to overview] | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment |
| NCT00463385 (10) [back to overview] | Time to the First Clinical Response |
| NCT00463385 (10) [back to overview] | Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment |
| NCT00463385 (10) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores |
| NCT00463385 (10) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00463385 (10) [back to overview] | Change From Baseline in Hemoglobin Concentration for Responders |
| NCT00463385 (10) [back to overview] | Change From Baseline in Likert Abdominal Pain Scale |
| NCT00463385 (10) [back to overview] | Duration of First Clinical Response |
| NCT00463385 (10) [back to overview] | Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment |
| NCT00537511 (7) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Recovery Period or Maintenance (Monotherapy) Phase |
| NCT00537511 (7) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the MTD (Combination Treatment) Phase |
| NCT00537511 (7) [back to overview] | Overall Survival |
| NCT00537511 (7) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs) During the MTD Phase |
| NCT00537511 (7) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00537511 (7) [back to overview] | Duration of Response |
| NCT00537511 (7) [back to overview] | Tumor Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00540579 (2) [back to overview] | Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects |
| NCT00540579 (2) [back to overview] | The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0 |
| NCT00558896 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT00558896 (3) [back to overview] | Duration of Response |
| NCT00558896 (3) [back to overview] | The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response) |
| NCT00669578 (4) [back to overview] | Determine the Maximum Tolerated Dose of CC-4047 |
| NCT00669578 (4) [back to overview] | Number of Participants With Treatment Related Adverse Events. |
| NCT00669578 (4) [back to overview] | Best Overall Response Over the First 6 Cycles of Treatment |
| NCT00669578 (4) [back to overview] | Duration of Response Time |
| NCT00717522 (1) [back to overview] | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, or Discontinuations Due to AEs |
| NCT00770757 (5) [back to overview] | Chronic Graft-versus-host Disease Global Score at the Start/End of the Study |
| NCT00770757 (5) [back to overview] | Overall Response (Complete Response + Partial Response + Other) |
| NCT00770757 (5) [back to overview] | Safety as Measured by the Most Common Adverse Effects and Reasons for Dose Reductions or Study-discontinuation |
| NCT00770757 (5) [back to overview] | Organ System Response |
| NCT00770757 (5) [back to overview] | Survival Rate of CC-4047 Responders |
| NCT00833833 (10) [back to overview] | Phase 2: Time to Response as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Kaplan-Meier Estimates of Duration of Response as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Kaplan-Meier Estimates of Overall Survival as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Kaplan-Meier Estimates of Progression-free Survival (PFS) as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Percentage of Participants With Progression-Free Survival (PFS) Events as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Pomalidomide and Dexamethasone as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Single-Agent Pomalidomide as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 2: Summary of Best Myeloma Response As Assessed by Independent Response Adjudication Committee (IRAC) Using European Group for Blood and Bone Marrow Transplant (EBMT) Criteria as of the 01 April 2011 Cut-off |
| NCT00833833 (10) [back to overview] | Phase 1: Participants With Dose-Limiting Toxicities (DLT) in Cycle 1 |
| NCT00946270 (1) [back to overview] | Number of Participants With Best Overall Response |
| NCT01078974 (2) [back to overview] | Maximum Tolerated Dose of Pomalidomide |
| NCT01078974 (2) [back to overview] | Tolerability of Pomalidomide |
| NCT01159574 (2) [back to overview] | Time to Disease Progression (Progression Free Survival) |
| NCT01159574 (2) [back to overview] | Time to Maximum Response, Expressed as Number of Cycles of Treatment to Maximum Response |
| NCT01177735 (1) [back to overview] | Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy |
| NCT01178281 (9) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score |
| NCT01178281 (9) [back to overview] | Change From Baseline in EuroQoL-5D (EQ-5D) Visual Analog Scale |
| NCT01178281 (9) [back to overview] | Change From Baseline in EuroQoL-5D (EQ-5D) Health Index Score |
| NCT01178281 (9) [back to overview] | Overall Survival |
| NCT01178281 (9) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (TEAE) |
| NCT01178281 (9) [back to overview] | Percentage of Participants Who Achieved RBC-Transfusion Independence |
| NCT01178281 (9) [back to overview] | Time to RBC-Transfusion Independence |
| NCT01178281 (9) [back to overview] | China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days |
| NCT01178281 (9) [back to overview] | Duration of RBC-Transfusion Independence |
| NCT01212952 (3) [back to overview] | Progression Free Survival |
| NCT01212952 (3) [back to overview] | Number of Participants With Adverse Events |
| NCT01212952 (3) [back to overview] | Find Maximum Tolerated Dose (MTD) of Bortezomib in Combination With Pomalidomide and Dexamethasone Out to 2.5 Years, by Count of Patients With Dose Limiting Toxicities. |
| 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 Overall Clinicohematologic Response at Week 32 |
| NCT01243944 (13) [back to overview] | Duration of The Overall Clinicohematologic Response |
| NCT01243944 (13) [back to overview] | The Percentage of Participants Achieving a Durable Primary Response at Week 48 |
| 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 Who Achieved a Durable Complete Hematological Remission 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] | Duration of Reduction in Spleen Volume |
| NCT01243944 (13) [back to overview] | Duration of the Absence of Phlebotomy Eligibility |
| 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 Who Achieved Durable Spleen Volume Reduction at Week 48 |
| NCT01243944 (13) [back to overview] | Estimated Duration of the Complete Hematological Remission |
| NCT01243944 (13) [back to overview] | Estimated Duration of the Primary Response |
| NCT01311687 (24) [back to overview] | Progression-free Survival (PFS) - Primary Analysis |
| NCT01311687 (24) [back to overview] | Duration of Response |
| NCT01311687 (24) [back to overview] | Overall Survival - Primary Analysis |
| NCT01311687 (24) [back to overview] | Overall Survival Based on the Final Dataset |
| NCT01311687 (24) [back to overview] | Overall Survival With a Later Cut-off Date |
| NCT01311687 (24) [back to overview] | Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria |
| NCT01311687 (24) [back to overview] | Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria |
| NCT01311687 (24) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms |
| NCT01311687 (24) [back to overview] | Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain |
| NCT01311687 (24) [back to overview] | Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain |
| NCT01311687 (24) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain |
| NCT01311687 (24) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Pain Domain |
| NCT01311687 (24) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Fatigue Domain |
| NCT01311687 (24) [back to overview] | Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score |
| NCT01311687 (24) [back to overview] | Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain |
| NCT01311687 (24) [back to overview] | Time to the First Hemoglobin Improvement |
| NCT01311687 (24) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT01311687 (24) [back to overview] | Time to Progression |
| NCT01311687 (24) [back to overview] | Time to Improvement in Renal Function |
| NCT01311687 (24) [back to overview] | Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status |
| NCT01311687 (24) [back to overview] | Time to Improvement in Bone Pain |
| NCT01311687 (24) [back to overview] | Time to Response |
| NCT01311687 (24) [back to overview] | Time to First Worsening of Quality of Life (QOL) Domains |
| NCT01311687 (24) [back to overview] | Progression-free Survival (PFS) With a Later Cut-off Date |
| NCT01319422 (2) [back to overview] | Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria |
| NCT01319422 (2) [back to overview] | Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria |
| NCT01324947 (8) [back to overview] | Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria |
| NCT01324947 (8) [back to overview] | Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria |
| NCT01324947 (8) [back to overview] | Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment |
| NCT01324947 (8) [back to overview] | Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment |
| NCT01324947 (8) [back to overview] | Time to Response Based on IMWG and Assessed by the Investigator |
| NCT01324947 (8) [back to overview] | Kaplan-Meier Estimate for Overall Survival |
| NCT01324947 (8) [back to overview] | Number of Participants With Adverse Events and Type of Adverse Events |
| NCT01324947 (8) [back to overview] | Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG |
| 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 |
| NCT01421186 (8) [back to overview] | Pharmacokinetics: AUC Cycle 1+2 - Area Under the Time/Concentration Curve for MOR202 |
| NCT01421186 (8) [back to overview] | Progression-free Survival |
| NCT01421186 (8) [back to overview] | Time to Progression |
| NCT01421186 (8) [back to overview] | Pharmacokinetics: Cmax - Maximum Observed Serum Concentration for MOR202 |
| NCT01432600 (5) [back to overview] | Phase II - Median Overall Survival (OS) |
| NCT01432600 (5) [back to overview] | Phase II - Median Progression Free Survival (PFS) |
| NCT01432600 (5) [back to overview] | Phase II - Overall Response Rate (ORR) |
| NCT01432600 (5) [back to overview] | Phase II - Occurrence of Possibly Related Adverse Events (AEs) |
| NCT01432600 (5) [back to overview] | Phase I - Maximum Tolerated Dose (MTD) |
| NCT01495598 (18) [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) |
| NCT01495598 (18) [back to overview] | Area Under the Plasma Concentration Versus Time Curve (AUC) to the Last Timepoint (AUCLast) |
| NCT01495598 (18) [back to overview] | Self-Reported Health-Related Quality of Life (HRQL) Instrument: Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) |
| NCT01495598 (18) [back to overview] | Change Between Timepoints Baseline to 4 Weeks, Baseline to 8 Weeks, and Baseline to End of Treatment in Kaposi Sarcoma-Associated Herpesvirus (KSHV) Viral Load |
| NCT01495598 (18) [back to overview] | Human Immunodeficiency Virus (HIV) Viral Load |
| NCT01495598 (18) [back to overview] | Number of Dose-limiting Toxicities |
| NCT01495598 (18) [back to overview] | Change in Cytokines From Baseline to 4 Weeks, Baseline to 8 Weeks and End of Treatment |
| NCT01495598 (18) [back to overview] | Progression Free Survival (PFS) |
| NCT01495598 (18) [back to overview] | Antitumor Effect of a First Course of Pomalidomide |
| NCT01495598 (18) [back to overview] | Antitumor Effect of a Second Course of Pomalidomide |
| NCT01495598 (18) [back to overview] | Area Under the Curve Extrapolated to Infinity (AUCinf) |
| NCT01495598 (18) [back to overview] | Percentage of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions |
| NCT01495598 (18) [back to overview] | Time to Maximum Observed Serum Concentration of Pomalidomide (Cmax) |
| NCT01495598 (18) [back to overview] | Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide |
| NCT01495598 (18) [back to overview] | Number of Participants Who Responded to Each Question on the Self-Reported Health-Related Quality of Life (HRQL): Kaposi Sarcoma (KS) - Specific Questions |
| NCT01495598 (18) [back to overview] | Maximal Plasma Concentration (Cmax) of Pomalidomide |
| NCT01495598 (18) [back to overview] | Half-Life of Pomalidomide |
| NCT01495598 (18) [back to overview] | Change in Immune Cytokines Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Cluster of Differentiation 19 (CD19) Among Participants With and/or Without Human Immunodeficiency Virus (HIV) |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 76 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 64 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 12 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 76 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 64 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Task at Week 24 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 76 |
| NCT01559129 (33) [back to overview] | Change From Baseline in University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Total Score at Week 52/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 64 |
| NCT01559129 (33) [back to overview] | Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 24 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Magnitude of Effort at Week 12 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 24 |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time |
| NCT01559129 (33) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
| NCT01559129 (33) [back to overview] | Oxygen Saturation Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in Dyspnea Functional Impairment at Week 12 |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in Percent Predicted Forced Vital Capacity Over Time |
| NCT01559129 (33) [back to overview] | Change From Baseline in Modified Rodnan Skin Score Over Time |
| NCT01570387 (4) [back to overview] | Response to the Maximal Tolerated Dose |
| NCT01570387 (4) [back to overview] | Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 3 Milligram Dose |
| NCT01570387 (4) [back to overview] | Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 4 Milligram Dose |
| NCT01570387 (4) [back to overview] | Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 2 Milligram Dose |
| NCT01592370 (31) [back to overview] | Best Overall Response - Multiple Myeloma Group |
| NCT01592370 (31) [back to overview] | Best Overall Response - Multiple Myeloma Group |
| NCT01592370 (31) [back to overview] | Best Overall Response |
| NCT01592370 (31) [back to overview] | Progression Free Survival in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Percentage Change From Baseline in the Modified Severity Weighted Assessment Tool (mSWAT) Score |
| NCT01592370 (31) [back to overview] | Overall Survival |
| NCT01592370 (31) [back to overview] | Objective Response Rate in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Number of Participants That Experienced Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Number of Participants That Experienced Drug Related Grade 3-4 AEs |
| NCT01592370 (31) [back to overview] | Number of Participants That Experience Drug-related Grade 3-4 SAEs in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Duration of Response in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Duration of Response - Multiple Myeloma Group |
| NCT01592370 (31) [back to overview] | Duration of Response |
| NCT01592370 (31) [back to overview] | Progression Free Survival |
| NCT01592370 (31) [back to overview] | Number of Participants That Experienced Drug Related Grade 3-4 SAEs |
| NCT01592370 (31) [back to overview] | Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology |
| NCT01592370 (31) [back to overview] | Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Number of Participants That Experienced Drug-related Grade 3-4 AEs in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | Progression Free Survival Rate |
| NCT01592370 (31) [back to overview] | Progression Free Survival Rate |
| NCT01592370 (31) [back to overview] | Progression Free Survival Rate |
| NCT01592370 (31) [back to overview] | Number of Participants With PD-L1 Expression |
| NCT01592370 (31) [back to overview] | Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid |
| NCT01592370 (31) [back to overview] | Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver |
| NCT01592370 (31) [back to overview] | Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid |
| NCT01592370 (31) [back to overview] | Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver |
| NCT01592370 (31) [back to overview] | End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort |
| NCT01592370 (31) [back to overview] | End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort |
| NCT01688466 (2) [back to overview] | Toxicity |
| NCT01688466 (2) [back to overview] | Overall Response at 6 Months |
| NCT01712789 (9) [back to overview] | Pomalidomide Exposure - Apparent Volume of Distribution (V/F) |
| NCT01712789 (9) [back to overview] | Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F) |
| NCT01712789 (9) [back to overview] | Overall Response |
| NCT01712789 (9) [back to overview] | Kaplan Meier Estimate of Time to Progression |
| NCT01712789 (9) [back to overview] | Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines |
| NCT01712789 (9) [back to overview] | Kaplan Meier Estimate of Overall Survival (OS) |
| NCT01712789 (9) [back to overview] | Time to Response |
| NCT01712789 (9) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAE) |
| NCT01712789 (9) [back to overview] | Kaplan Meier Estimate of Duration of Response |
| NCT01734928 (6) [back to overview] | Duration of Response by Independent Response Adjudication Committee (IRAC) |
| NCT01734928 (6) [back to overview] | Number of Participants With Grade 3-4 Treatment Emergent Adverse Events (TEAE) |
| NCT01734928 (6) [back to overview] | Number of Participants With Grade 5 Treatment Emergent Adverse Events (TEAE) |
| NCT01734928 (6) [back to overview] | Overall Survival (OS) |
| NCT01734928 (6) [back to overview] | Progression Free Survival by Independent Response Adjudication Committee (IRAC) |
| NCT01734928 (6) [back to overview] | Overall Response Rate by Independent Response Adjudication Committee (IRAC) |
| NCT01754402 (2) [back to overview] | Initial Response Rate |
| NCT01754402 (2) [back to overview] | Maximum Tolerated Dose of Pomalidomide and Bendamustine |
| NCT01794039 (4) [back to overview] | Time to Progression |
| 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] | 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 |
| NCT01946152 (4) [back to overview] | Number of Participants With Progression-free Survival |
| NCT01946152 (4) [back to overview] | Number of Participants With Best Overall Response Defined Using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) |
| NCT01946152 (4) [back to overview] | Number of Participants Recommended Phase II Dose of Pomalidomide and Dexamethasone, When Both Agents Are Administered Together With Granulocyte-colony Stimulating Factor (Filgrastim) (Phase I) |
| NCT01946152 (4) [back to overview] | Maximum Tolerated Dose (MTD) (Phase I) |
| NCT01979276 (1) [back to overview] | Time to Disease Progression (Progression Free Survival) |
| NCT01999335 (10) [back to overview] | Number of Participants With Post-Baseline Grade 3 or 4 Laboratory Toxicities |
| NCT01999335 (10) [back to overview] | Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
| NCT01999335 (10) [back to overview] | Time to Maximum Plasma Concentration (Tmax) of Oprozomib |
| NCT01999335 (10) [back to overview] | Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib |
| NCT01999335 (10) [back to overview] | Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of Oprozomib |
| NCT01999335 (10) [back to overview] | Overall Response Rate (ORR) |
| NCT01999335 (10) [back to overview] | Maximum Plasma Concentration (Cmax) of Oprozomib |
| NCT01999335 (10) [back to overview] | Number of Participants With Dose-limiting Toxicities (DLTs) |
| NCT01999335 (10) [back to overview] | Clinical Benefit Rate (CBR) |
| NCT01999335 (10) [back to overview] | Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib |
| NCT02004275 (13) [back to overview] | Overall Response Rate (ORR) |
| NCT02004275 (13) [back to overview] | Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I) |
| NCT02004275 (13) [back to overview] | Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II) |
| NCT02004275 (13) [back to overview] | Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II) |
| NCT02004275 (13) [back to overview] | Progression Free Survival (PFS) (Phase II) |
| NCT02004275 (13) [back to overview] | Overall Survival (OS) (Phase II) |
| NCT02004275 (13) [back to overview] | Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II) |
| NCT02004275 (13) [back to overview] | Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II) |
| NCT02004275 (13) [back to overview] | Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II) |
| NCT02004275 (13) [back to overview] | Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I) |
| NCT02004275 (13) [back to overview] | Incidence of Dose Reductions/Delays (Phase I) |
| NCT02004275 (13) [back to overview] | Clinical Benefit Rate (CBR) |
| NCT02004275 (13) [back to overview] | Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II) |
| NCT02011113 (10) [back to overview] | Number of Participants With Adverse Events |
| NCT02011113 (10) [back to overview] | Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria |
| NCT02011113 (10) [back to overview] | Kaplan-Meier Estimates of Duration of Response (Later Cut-off Date) |
| NCT02011113 (10) [back to overview] | Kaplan-Meier Estimates of PFS (Later Cut-off Date) |
| NCT02011113 (10) [back to overview] | Kaplan-Meier Estimates of Progression-free Survival (PFS) |
| NCT02011113 (10) [back to overview] | Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria (Later Cut-off Date) |
| NCT02011113 (10) [back to overview] | Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria |
| NCT02011113 (10) [back to overview] | Myeloma Response Rate Based on the International Myeloma Working Group (IMWG) Uniform Response Criteria (Later Cut-off Date) |
| NCT02011113 (10) [back to overview] | Time to Response |
| NCT02011113 (10) [back to overview] | Time to Response (Later Cut-off Date) |
| NCT02119468 (7) [back to overview] | One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D) |
| NCT02119468 (7) [back to overview] | One-Year Overall Survival at the Recommended Phase II Dose (RP2D) |
| NCT02119468 (7) [back to overview] | Overall Response Rate at the Recommended Phase II Dose (RP2D) |
| NCT02119468 (7) [back to overview] | Maximum Tolerated Dose (MTD) of MLN9708 (Phase I) |
| NCT02119468 (7) [back to overview] | Clinical Benefit Response Rate at the Recommended Phase II Dose (RP2D) |
| NCT02119468 (7) [back to overview] | Duration of Response at the Recommended Phase II Dose (RP2D) |
| NCT02119468 (7) [back to overview] | Number of Patients With Dose-Limiting Toxicities (Phase I) |
| 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 and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment |
| 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, 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: 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: Tmax: Time to Maximum Plasma Concentration for Itacitinib |
| NCT02265510 (10) [back to overview] | Phase 2: Number of Participants With at Least One TEAE and SAE |
| 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 2: Objective Response Rate (ORR) in Hematological Malignancies |
| NCT02289222 (3) [back to overview] | PD-LI Expression On Myeloma Cells |
| NCT02289222 (3) [back to overview] | Time to Progression Free Survival (PFS) |
| NCT02289222 (3) [back to overview] | The Number of Participants With Adverse Events |
| NCT02547662 (5) [back to overview] | Extramedullary Response Rate |
| NCT02547662 (5) [back to overview] | Biochemical Response Rate |
| NCT02547662 (5) [back to overview] | Confirmed Response Rate |
| NCT02547662 (5) [back to overview] | Progression-free Survival |
| NCT02547662 (5) [back to overview] | Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 |
| NCT02548962 (3) [back to overview] | Clinical Benefit Response (CBR) |
| NCT02548962 (3) [back to overview] | Duration of Response (DOR) |
| NCT02548962 (3) [back to overview] | Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment |
| NCT02576977 (6) [back to overview] | Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review |
| NCT02576977 (6) [back to overview] | Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review |
| NCT02576977 (6) [back to overview] | Overall Survival (OS) |
| NCT02576977 (6) [back to overview] | Participants Discontinuing Study Investigational Product Due to an AE |
| NCT02576977 (6) [back to overview] | Participants Experiencing One or More Adverse Events (AEs) |
| NCT02576977 (6) [back to overview] | Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria |
| NCT02612779 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT02612779 (3) [back to overview] | Objective Response Rate (ORR) |
| NCT02612779 (3) [back to overview] | Overall Survival (OS) |
| NCT02654132 (3) [back to overview] | Overall Survival (OS) |
| NCT02654132 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT02654132 (3) [back to overview] | Objective Response Rate (ORR) |
| NCT02726581 (5) [back to overview] | Time to Objective Response (TTR) |
| NCT02726581 (5) [back to overview] | Overall Survival (OS) |
| NCT02726581 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT02726581 (5) [back to overview] | Objective Response Rate (ORR) |
| NCT02726581 (5) [back to overview] | Duration of Objective Response (DOR) |
| NCT02807454 (12) [back to overview] | Time-To-Response (TTR) |
| NCT02807454 (12) [back to overview] | Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Number of Participants With Serious Adverse Events (SAEs) |
| NCT02807454 (12) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT02807454 (12) [back to overview] | Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm |
| NCT02807454 (12) [back to overview] | Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Overall Response Rate (ORR) |
| NCT02807454 (12) [back to overview] | Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Simon Stage 1: D2 Arm |
| NCT02807454 (12) [back to overview] | Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm |
| NCT02990338 (24) [back to overview] | Time to Progression (TTP) as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Time to First Response (TT1R) as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Time to Best Response (TTBR) as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Progression Free Survival in High Risk Cytogenetic Population |
| NCT02990338 (24) [back to overview] | Progression Free Survival (PFS) |
| NCT02990338 (24) [back to overview] | Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Overall Survival (OS): Final Analysis |
| NCT02990338 (24) [back to overview] | Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC) |
| NCT02990338 (24) [back to overview] | Duration of Response (DOR) as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Number of Participants With Anti-drug Antibodies (ADA) |
| NCT02990338 (24) [back to overview] | Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) |
| NCT02990338 (24) [back to overview] | Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value |
| NCT02990338 (24) [back to overview] | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score |
| NCT02990338 (24) [back to overview] | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score |
| NCT02990338 (24) [back to overview] | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score |
| NCT02990338 (24) [back to overview] | PK Parameter: Plasma Concentration of Isatuximab at Ctrough |
| NCT02990338 (24) [back to overview] | PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough) |
| NCT02990338 (24) [back to overview] | Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) |
| NCT02990338 (24) [back to overview] | Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour) |
| NCT02990338 (24) [back to overview] | Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI) |
| NCT02990338 (24) [back to overview] | Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee |
| NCT02990338 (24) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT02990338 (24) [back to overview] | Number of Participants With Minimal Residual Disease (MRD) |
| NCT03030261 (3) [back to overview] | Complete Response Rate (CRR) |
| NCT03030261 (3) [back to overview] | Event-free Survival (EFS) Rate |
| NCT03030261 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT03151811 (4) [back to overview] | Safety and Tolerability: Number of Patients With Treatment-emergent Adverse Events, Including Clinical Laboratory and Vital Signs Abnormalities, as Assessed by CTCAE v4.0 |
| NCT03151811 (4) [back to overview] | Duration of Response (DOR) |
| NCT03151811 (4) [back to overview] | Overall Response Rate (ORR) |
| NCT03151811 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT03170882 (13) [back to overview] | Overall Survival (OS) |
| NCT03170882 (13) [back to overview] | HRQOL Based on EORTC QLQ-C30 SubScale Score |
| NCT03170882 (13) [back to overview] | HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score |
| NCT03170882 (13) [back to overview] | Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score |
| NCT03170882 (13) [back to overview] | Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter |
| NCT03170882 (13) [back to overview] | Time to Progression (TTP) |
| NCT03170882 (13) [back to overview] | Progression Free Survival (PFS) |
| NCT03170882 (13) [back to overview] | Percentage of Participants With Overall Response |
| NCT03170882 (13) [back to overview] | Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score |
| NCT03170882 (13) [back to overview] | Time to Response |
| NCT03170882 (13) [back to overview] | HU: Duration of Medical Encounters |
| NCT03170882 (13) [back to overview] | Duration of Response (DOR) |
| NCT03170882 (13) [back to overview] | HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score |
| NCT03180736 (8) [back to overview] | Health-related Quality of Life-Time to Worsening in EQ-5D-5L Utility Score |
| NCT03180736 (8) [back to overview] | Health-related Quality of Life-Time to Worsening in EQ-5D-5L Visual Analogue Scale |
| NCT03180736 (8) [back to overview] | Overall Response Rate |
| NCT03180736 (8) [back to overview] | Time to Next Therapy |
| NCT03180736 (8) [back to overview] | Depth of Response |
| NCT03180736 (8) [back to overview] | Comparison of Progression Free Survival Between Treatment Arms |
| NCT03180736 (8) [back to overview] | Health-related Quality of Life-Time to Worsening in EORTC QLQ-C30 Scale Scores |
| NCT03180736 (8) [back to overview] | Duration of Response |
| NCT03202628 (5) [back to overview] | Overall Response Rate |
| NCT03202628 (5) [back to overview] | Number of Patients Experiencing Adverse Events Graded According to the Medical Dictionary for Regulatory Activities (MedDRA) Version (v) 12.1 |
| NCT03202628 (5) [back to overview] | Percentage of Participants With Greater Than or Equal to (>=) Very Good Partial Response (VGPR) Rate |
| NCT03202628 (5) [back to overview] | Progression-free Survival at 18 Months (PFS18) Defined as the Proportion of Patients Alive and Free From Disease Progression at 18 Months From Study Entry |
| NCT03202628 (5) [back to overview] | Percent of Patients Alive at 30 Months |
| NCT03257631 (7) [back to overview] | Kaplan-Meier Estimate of Progression-Free Survival (PFS) |
| NCT03257631 (7) [back to overview] | Percentage of Participants With Long-term Stable Disease |
| NCT03257631 (7) [back to overview] | Percentage of Participants With an Objective Response or Long-term Stable Disease |
| NCT03257631 (7) [back to overview] | Percentage of Participants Who Achieved an Objective Response |
| NCT03257631 (7) [back to overview] | Kaplan-Meier Estimate of Duration of Response |
| NCT03257631 (7) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
| NCT03257631 (7) [back to overview] | Kalan-Meier Estimate of Overall Survival |
| NCT03439280 (13) [back to overview] | Phase 1: RP2D of TAK-079 |
| NCT03439280 (13) [back to overview] | Phase 1: Overall Response Rate (ORR) |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants With TEAEs Leading to Treatment Discontinuation |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants With TEAEs Leading to Dose Modifications |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants With Serious TEAEs |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants With Grade 3 or Higher TEAEs |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) |
| NCT03439280 (13) [back to overview] | Phase 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
| NCT03439280 (13) [back to overview] | Percentage of Participants With Positive Anti-drug Antibodies (ADA) |
| NCT03439280 (13) [back to overview] | Percentage of Participants With Minimal Response (MR) |
| NCT03439280 (13) [back to overview] | Cmax: Maximum Observed Serum Concentration for TAK-079 |
| NCT03439280 (13) [back to overview] | Tmax: Time to Reach the Maximum Observed Serum Concentration (Cmax) for TAK-079 |
| NCT03439280 (13) [back to overview] | AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079 |
| NCT03440411 (1) [back to overview] | Overall Survival (OS) |
| NCT03567616 (5) [back to overview] | Duration of Response (DOR) |
| NCT03567616 (5) [back to overview] | Progression-Free Survival (PFS) |
| NCT03567616 (5) [back to overview] | Time-to-progression (TTP) |
| NCT03567616 (5) [back to overview] | Number of Participants With Adverse Events |
| NCT03567616 (5) [back to overview] | Overall Response Rate (ORR) |
| NCT04162210 (1) [back to overview] | Progression-free Survival (PFS) Based on Investigator-assessed Response as Per International Myeloma Working Group (IMWG) |
| NCT04191616 (2) [back to overview] | Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) (PA DCO Only) |
| NCT04191616 (2) [back to overview] | Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC (PA DCO Only) |
| NCT04843579 (2) [back to overview] | Number of Participants With Adverse Events |
| NCT04843579 (2) [back to overview] | Percentage of Participants With Overall Response Rate of Partial Response or Better |
Change From Baseline in Hemoglobin Concentration for Non-Responders
Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment. (NCT00463385)
Timeframe: Baseline, Cycle 6 (168 days)
| Intervention | g/dL (Median) |
|---|
| Prednisone | 1.2 |
| Pomalidomide 2 mg | 0.1 |
| Pomalidomide 2 mg + Prednisone | -0.8 |
| Pomalidomide 0.5 mg + Prednisone | 0.5 |
Percentage of Participants With Clinical Response by Baseline JAK2 Assessment
Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline. (NCT00463385)
Timeframe: Up to 336 days
| Intervention | percentage of participants (Number) |
|---|
| Prednisone, Positive JAK2 | 46.2 |
| Pomalidomide 2 mg, PositiveJAK2 | 27.3 |
| Pomalidomide 2 mg + Prednisone, Positive JAK2 | 30.0 |
| Pomalidomide 0.5 mg + Prednisone, Positive JAK2 | 66.7 |
| Prednisone, Negative JAK2 | 50.0 |
| Pomalidomide 2 mg, Negative JAK2 | 28.6 |
| Pomalidomide 2 mg + Prednisone, Negative JAK2 | 12.5 |
| Pomalidomide 0.5 mg + Prednisone, Negative JAK2 | 25.0 |
Time to the First Clinical Response
"The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as:~Start date of the first clinical response - the first study drug date +1.~A clinical responder was defined as either:~A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or~A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or~A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable." (NCT00463385)
Timeframe: Up to 168 days
| Intervention | weeks (Median) |
|---|
| Prednisone | 0.3 |
| Pomalidomide 2 mg | 8.0 |
| Pomalidomide 2 mg + Prednisone | 10.1 |
| Pomalidomide 0.5 mg + Prednisone | 1.2 |
Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
"A clinical responder was defined as either:~A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or~A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or~A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.~Participants who discontinued the study early without achieving clinical response were counted as non-responders." (NCT00463385)
Timeframe: Up to 168 days
| Intervention | percentage of participants (Number) |
|---|
| Prednisone | 55.0 |
| Pomalidomide 2 mg | 23.5 |
| Pomalidomide 2 mg + Prednisone | 21.1 |
| Pomalidomide 0.5 mg + Prednisone | 47.6 |
Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores
"The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life.~Physical Well-being consists of 7 questions, the subscale score ranges from 0-28;~Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28;~Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24;~Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28;~Anemia subscale consists of 20 questions, the subscale score ranges from 0-80;~Total FACT-An score ranges from 0-188." (NCT00463385)
Timeframe: Baseline and Cycle 6 (168 days).
| Intervention | units on a scale (Mean) |
|---|
| Physical Well-Being subscale | Social/Family Well-Being subscale | Emotional Well-Being subscale | Functional Well-Being subscale | Anemia subscale | Total FACT-An score |
|---|
| Pomalidomide 0.5 mg + Prednisone | 2.3 | 0.9 | 1.7 | 2.5 | 5.8 | 11.4 |
,| Pomalidomide 2 mg | 0.4 | -1.9 | 0.0 | -2.1 | 2.3 | 1.6 |
,| Pomalidomide 2 mg + Prednisone | 5.3 | 1.7 | -0.3 | 2.7 | 19.3 | 27.3 |
,| Prednisone | 0.6 | 1.9 | 1.3 | 0.9 | 1.2 | 2.3 |
Number of Participants With Adverse Events (AEs)
"A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above).~The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale:~Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death.~The Investigator determined the relationship between study drug and the occurrence of an AE as Not Related or Related (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa)." (NCT00463385)
Timeframe: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).
| Intervention | participants (Number) |
|---|
| At least one AE | At least one AE related to pomalidomide | At least one AE related to prednisone | At least one Grade 3-4 AE | At least one Grade 3-4 AE related to pomalidomide | At least one Grade 3-4 AE related to prednisone | At least one SAE | At least one SAE related to pomalidomide | At least one SAE related to prednisone | AE leading to discontinuation of pomalidomide | AE leading to discontinuation of prednisone | AE leading to a dose reduction of pomalidomide | AE leading to a dose interruption of pomalidomide | AE leading to a dose interruption of prednisone |
|---|
| Pomalidomide 0.5 mg + Prednisone | 21 | 15 | 5 | 15 | 6 | 3 | 8 | 3 | 3 | 6 | 1 | 1 | 7 | 3 |
,| Pomalidomide 2 mg | 21 | 17 | 10 | 14 | 7 | 2 | 10 | 6 | 3 | 11 | 7 | 2 | 9 | 8 |
,| Pomalidomide 2 mg + Prednisone | 18 | 16 | 11 | 13 | 11 | 6 | 11 | 8 | 5 | 5 | 2 | 1 | 9 | 6 |
,| Prednisone | 20 | 15 | 10 | 10 | 6 | 5 | 6 | 4 | 4 | 7 | 5 | 0 | 5 | 2 |
Change From Baseline in Hemoglobin Concentration for Responders
Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment. (NCT00463385)
Timeframe: Baseline, Cycle 6 (168 days)
| Intervention | g/dL (Median) |
|---|
| Prednisone | 1.4 |
| Pomalidomide 2 mg | 2.0 |
| Pomalidomide 0.5 mg + Prednisone | -0.1 |
Change From Baseline in Likert Abdominal Pain Scale
Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable. (NCT00463385)
Timeframe: Baseline and Cycle 6 (168 days)
| Intervention | units on a scale (Mean) |
|---|
| Prednisone | 0.3 |
| Pomalidomide 2 mg | -1.0 |
| Pomalidomide 2 mg + Prednisone | 0.3 |
| Pomalidomide 0.5 mg + Prednisone | -0.1 |
Duration of First Clinical Response
"For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment.~For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of < 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement.~Kaplan-Meier methodology was used." (NCT00463385)
Timeframe: Up to 40 months
| Intervention | months (Median) |
|---|
| Prednisone | 3.7 |
| Pomalidomide 2 mg | NA |
| Pomalidomide 2 mg + Prednisone | 6.0 |
| Pomalidomide 0.5 mg + Prednisone | 10.6 |
Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment
"A clinical responder was defined as either:~A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or~A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or~A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable.~Participants who discontinued the study early without achieving clinical response were counted as non-responders." (NCT00463385)
Timeframe: Up to 336 days
| Intervention | percentage of participants (Number) |
|---|
| Prednisone | 50.0 |
| Pomalidomide 2 mg | 18.2 |
| Pomalidomide 2 mg + Prednisone | 18.2 |
| Pomalidomide 0.5 mg + Prednisone | 45.5 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Recovery Period or Maintenance (Monotherapy) Phase
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 participant's health, including laboratory test values, regardless of etiology. 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. (NCT00537511)
Timeframe: Cycle 7 to discontinuation (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide during Maintenance Phase was 5.0 (1.1, 36.0).
| Intervention | participants (Number) |
|---|
| ≥1 TEAE | ≥1 TEAE related to pomalidomide (POM) | ≥1 TEAE related to cisplatin and/or etoposide (C/E | ≥1 Grade 3 or higher (GR3+) TEAE | ≥1 GR 3+ TEAE related to POM | ≥1 GR 3+ TEAE related to C/E | ≥1 TEAE → dose reduction/interruption of POM |
|---|
| Pomalidomide (Overall) | 9 | 8 | 7 | 6 | 2 | 2 | 2 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the MTD (Combination Treatment) Phase
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 participant's 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. (NCT00537511)
Timeframe: Cycles 1-6 (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide (MTD Phase): 1 mg, 17.9 (1.0, 20.3); 3 mg, 17.0 (16.9, 22.0); 4 mg, 14.0 (0.7, 22.0); 5 mg, 13.0 (2.0, 22.1). Cisplatin and etoposide: 15.3 (0.4, 20.6).
| Intervention | participants (Number) |
|---|
| ≥1 TEAE | ≥1 TEAE related to pomalidomide (POM) | ≥1 TEAE related to cisplatin and/or etoposide(C/E) | ≥1 Grade 3 or higher (GR3+) TEAE | ≥1 GR 3+ TEAE related to POM | ≥1 GR 3+ TEAE related to C/E | ≥1 Serious TEAE | ≥1 Serious TEAE related to POM | ≥1 Serious TEAE related to C/E | ≥1 TEAE leading to (→) withdrawal of POM | ≥1 TEAE → withdrawal of C/E | ≥1 TEAE → dose reduction/interruption of POM | ≥1 TEAE → dose reduction/interruption of C/E |
|---|
| Pomalidomide (Overall, MTD Phase) | 22 | 22 | 22 | 22 | 14 | 20 | 10 | 7 | 9 | 6 | 6 | 15 | 13 |
,| Pomalidomide 1 mg | 6 | 6 | 6 | 6 | 3 | 6 | 3 | 2 | 2 | 2 | 2 | 5 | 3 |
,| Pomalidomide 3 mg | 4 | 4 | 4 | 4 | 2 | 3 | 1 | 1 | 1 | 0 | 1 | 2 | 3 |
,| Pomalidomide 4 mg | 6 | 6 | 6 | 6 | 4 | 6 | 3 | 1 | 3 | 2 | 1 | 4 | 3 |
,| Pomalidomide 5 mg | 6 | 6 | 6 | 6 | 5 | 5 | 3 | 3 | 3 | 2 | 2 | 4 | 4 |
Overall Survival
Overall Survival was defined as time (in weeks) from enrollment to death. The median is based on Kaplan-Meier estimate, with 95% confidence intervals about the median overall survival. Overall survival was censored at the last time participant was known to be alive for those who were alive at time of analysis. (NCT00537511)
Timeframe: From enrollment through study termination (approximately 35 months)
| Intervention | weeks (Median) |
|---|
| Pomalidomide (Overall) | 49.6 |
Number of Participants With Dose Limiting Toxicities (DLTs) During the MTD Phase
For the purposes of determining the MTD (see Primary Outcome Measure), a DLT was defined as any 1 or more of the following: inability to deliver all 3 doses of cisplatin and etoposide due to toxicity; inability to deliver 14 consecutive days of daily pomalidomide dosing because the participant did not tolerate the medication due to any of the following: ≥ grade 3 non-hematological toxicity (excluding alopecia) occurring before Day 14 of pomalidomide dosing; febrile neutropenia (absolute neutrophil count [ANC] <1,000/µL and fever >101ºF, core temperature); grade 4 neutropenia of ≥7 days duration with onset on or before Day 14 of pomalidomide dosing; platelet count <25,000/µL occurring before Day 14 of pomalidomide dosing. 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. (NCT00537511)
Timeframe: Cycles 1 - 6 (21-day cycles)
| Intervention | participants (Number) |
|---|
| Pomalidomide 1 mg | 1 |
| Pomalidomide 3 mg | 0 |
| Pomalidomide 4 mg | 0 |
| Pomalidomide 5 mg | 2 |
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. The MTD Phase included the Treatment period (Cycle 1: Identification of the MTD) and the Extension period (Cycles 2 to 6: Confirmation of Safety of the MTD). (See Secondary Outcome Measure 2 for data on DLTs.) (NCT00537511)
Timeframe: Cycle 1 (21 days)
| Intervention | mg (Number) |
|---|
| Pomalidomide (Overall) | 4 |
Duration of Response
Duration of Response was calculated from first Partial Response (PR) or Complete Response (CR) to disease progression. Duration of response was censored at the last date that the participant was known to be progression-free for: 1) participants who had not progressed at the time of analysis; 2) participants who had been removed from the treatment phase prior to documentation of progression. (NCT00537511)
Timeframe: From first Partial Response (PR) or Complete Response (CR) to disease progression (maximum of 19.4 weeks)
| Intervention | weeks (Mean) |
|---|
| Pomalidomide (Overall) | 13.2 |
Tumor Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST)
Investigator's best assessment of response based on RECIST criteria during the MTD phase. For target lesions: Complete Response (CR)=Disappearance of all target lesions; Partial Response (PR)=≥30% decrease in sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD; Progressed Disease (PD)=≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or the appearance of ≥1 new lesions; Stable Disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since treatment started. For non-target lesions: CR= Disappearance of all non-target lesions and normalization of tumor marker level; Incomplete Response/SD=Persistence of ≥1 non-target lesions and/or maintenance of tumor marker level above normal limits; PD=Appearance of ≥1 new lesions; unequivocal progression of existing non-target lesions. (NCT00537511)
Timeframe: Cycles 1 -6 (21-day cycles)
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | No Change/Stable Disease | Progressive Disease | Not Assessed | Missing |
|---|
| Pomalidomide (Overall, MTD Phase) | 0 | 11 | 0 | 4 | 1 | 6 |
,| Pomalidomide 1 mg | 0 | 3 | 0 | 1 | 0 | 2 |
,| Pomalidomide 3 mg | 0 | 3 | 0 | 1 | 0 | 0 |
,| Pomalidomide 4 mg | 0 | 2 | 0 | 1 | 1 | 2 |
,| Pomalidomide 5 mg | 0 | 3 | 0 | 1 | 0 | 2 |
Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects
"Unacceptable side effects or dose-limiting toxicities (DLTs) were defined as follows:~Inability to Complete cycle 1 of therapy due to drug-related toxicity.~> Grade 3 non-hematological drug-related toxicity (excluding alopecia) despite optimal supportive care~Febrile neutropenia (absolute neutrophil count [ANC] <1,000/μL and fever >101° F (38.5° C))~Grade 4 neutropenia that occurs prior to day 21. (Grade 4 neutropenia that occurs after day 21 but resolves within 7 days of the scheduled cycle 2, will not be considered DLT)~Platelet count < 25,000/μL~Inability to initiate Cycle 2, Day 1 therapy within 7 days of scheduled start (i.e. cannot delay the start of Cycle 2 by more than 7 days following the normal 7 day recovery period) due to drug-related toxicity." (NCT00540579)
Timeframe: 6 months
| Intervention | milligrams (Number) |
|---|
| Pomalidomide | Gemcitabine |
|---|
| Pomalidomide/Gemcitabine | 10 | 1000 |
The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0
The relative incidence of Grade 3/4 adverse events from protocol treatment as defined by Common Terminology Criteria for Adverse Events v3.0 (CTCAE) (NCT00540579)
Timeframe: 24 Months
| Intervention | percentage of patients (Number) |
|---|
| Pomalidomide/Gemcitabine | 39 |
Progression Free Survival (PFS)
"PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method.~Progression was defined as any one or 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" (NCT00558896)
Timeframe: Duration of study (up to 5 years)
| Intervention | months (Median) |
|---|
| Relapsed Myeloma (<4 Prior Regimens): Low Dose | 13 |
| Lenalidomide Refractory Myeloma: Low Dose | 5 |
| Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose | 6.4 |
| Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose | 3.3 |
| Relapsed Myeloma (< 4 Prior Regimens): High Dose | 7.7 |
| Relapsed/Refractory Myeloma: High Dose | 4.3 |
| Relapsed Amyloidosis: Low Dose | 14.1 |
Duration of Response
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. Kaplan Meier method was used to compute this outcome. (NCT00558896)
Timeframe: Duration of study (up to 5 years)
| Intervention | months (Median) |
|---|
| Relapsed Myeloma (<4 Prior Regimens): Low Dose | 21.3 |
| Lenalidomide Refractory Myeloma: Low Dose | 8.2 |
| Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose | 15.6 |
| Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose | 3.1 |
| Relapsed Myeloma (< 4 Prior Regimens): High Dose | NA |
| Relapsed/Refractory Myeloma: High Dose | 8.3 |
| Relapsed Amyloidosis: Low Dose | 19 |
The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response)
"Response that was confirmed on 2 consecutive evaluations~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 <100mg per 24hours; <=5% plasma cells in bone marrow.~Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels." (NCT00558896)
Timeframe: Duration of study (up to 3 years)
| Intervention | participants (Number) |
|---|
| Relapsed Myeloma (<4 Prior Regimens): Low Dose | 39 |
| Lenalidomide Refractory Myeloma: Low Dose | 11 |
| Bortezomib/Lenalidomide Refractory/Relapsed Myeloma: Low Dose | 9 |
| Bortezomib/Lenalidomide Relapsed/Refractory Myeloma: High Dose | 10 |
| Relapsed Myeloma (< 4 Prior Regimens): High Dose | 23 |
| Relapsed/Refractory Myeloma: High Dose | 25 |
| Relapsed Amyloidosis: Low Dose | 16 |
Determine the Maximum Tolerated Dose of CC-4047
Starting at a dose level of 2.5 mg/d on days 1-21 in every 28 day cycle, participants were accrued in cohorts of three to assess dose limiting toxicities (DLT) and determine the maximum tolerated dose (MTD). Dose escalation at increments of 0.5 mg/d was done if no subject had a DLT (a grade 4 or higher hematologic toxicity or a grade 3 or higher febrile neutropenia or a grade 3 or higher non-hematologic toxicity) in cycle 1. Subsequent cohorts were treated until the maximum tolerated dose (MTD) was reached (dose level before that which results in a DLT in >1 of 6 subjects). Subsequent participants were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal efficacious dose (MED) of 0.5 mg daily. Here, we are reporting the percentage of participants in Phase I with a DLT at each dose level. (NCT00669578)
Timeframe: The first 28-day cycle of treatment.
| Intervention | percentage of participants with DLT (Number) |
|---|
| 2.5 mg/day | 3.0 mg/day | 3.5 mg/day |
|---|
| Phase I | 0 | 0 | 66 |
Best Overall Response Over the First 6 Cycles of Treatment
"Response evaluation:~Complete Remission (CR):~Neutrophil count between 1 to 10 x 10^9/L without peripheral blasts in blood or bone marrow.~Partial Hematologic Response/Partial Remission (PR):~Increase in neutrophil by 50% + above 10^9/L for neutropenia)~Clinical Improvement (CI):~Increase in Neutrophil count, hemoglobin, platelet count or reduction in blood/marrow blasts." (NCT00669578)
Timeframe: Every cycle of treatment for 6 cycles. Each cycle is 28 days.
| Intervention | participants (Number) |
|---|
| Complete Remission | Partial Remission | Clinical Improvement |
|---|
| Phase II | 0 | 0 | 9 |
Duration of Response Time
Duration of response is defined as the date at which the patient's objective status is first noted to be a CR, PR or CI to the date progression is documented (if one has occurred) or to the date of last follow-up(for those patients who have not progressed). (NCT00669578)
Timeframe: Time from response to disease progression, intolerance of study drug, or death.
| Intervention | Months (Median) |
|---|
| Phase II | 5.6 |
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, or Discontinuations Due to AEs
An adverse event (AE) is defined as any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a study subject 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 study subject's health, including laboratory test values, regardless of etiology. A serious adverse event (SAE) 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; constitutes an important medical event. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death. For more details, please see the Adverse Events section of this record. (NCT00717522)
Timeframe: AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. Median treatment duration was 49 days (range: 3 to 102 days).
| Intervention | participants (Number) |
|---|
| ≥1 AE | ≥1 AE suspected to be related to study drug | ≥1 Grade 3 AE | ≥1 Grade 4 AE | ≥1 SAE | ≥1 SAE suspected to be related to study drug | Death | Death within 30 days of last dose of study drug | Discontinuation due to AE | Dose reduction and interruption due to AE |
|---|
| Pomalidomide | 7 | 6 | 4 | 1 | 3 | 1 | 4 | 1 | 2 | 1 |
Chronic Graft-versus-host Disease Global Score at the Start/End of the Study
"Global scoring of chronic GvHD consists of questions about various organs including skin, genital tract, lungs, liver, and multiple others. The physician scores each organ from 0 to 3. Score 0 means the patient has no symptoms. Score 1 means the patient has mild symptoms. Score 2 means the patient has moderate symptoms. Score 3 means the patient has severe syptoms.~Mild scoring of chronic GvHD is only 1 or 2 organs or site (except the lung). No clinically significant functional impairment (maximum of score 1 in all affected organs or sites)~Moderate scoring of chronic GvHD is at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) or 3 or more organs or sites with no clinically significant functional impairment (maximum of 1 in all affected orgnas or sites)~Severe scoring of chronic GvHD is a major disability caused by chronic GvHD (score of 3 in any organ or site) and lung function score >=2." (NCT00770757)
Timeframe: 1 year after last dose of CC-4047
| Intervention | participants (Number) |
|---|
| Starting score Severe/Ending score Severe | Starting score Moderate/Ending score Moderate |
|---|
| CC-4047 Arm | 11 | 2 |
Overall Response (Complete Response + Partial Response + Other)
"CR is defined as complete resolution in all of signs and symptoms at all affected organs and tissues~PR is defined as improvement in greater than or equal to 1 organ/tissue with no progression in any other affected organ/tissue~Improvement in chronic GvHD symptoms less than what meets the definition of a PR is defined as other~Progressive disease is defined as failure of therapy to control chronic GvHD despite increasing the dose of primary therapy or adding second line treatments~No response is defined as no change in disease." (NCT00770757)
Timeframe: 1 year after last dose of CC-4047
| Intervention | participants (Number) |
|---|
| Partial overall response | No response | Complete overall response | Progressive disease |
|---|
| CC-4047 Arm | 7 | 2 | 0 | 0 |
Safety as Measured by the Most Common Adverse Effects and Reasons for Dose Reductions or Study-discontinuation
-Toxicities will be graded according to the NCI CTCAE v3.0. (NCT00770757)
Timeframe: 30 days after last dose of CC-4047 or until resolution of event
| Intervention | participants (Number) |
|---|
| Tremors/shakiness | Muscle cramps/musculoskeletal pain | Fatigue/anxiety | Sensory neuropathy | Respiratory syncytial virus (RSV) pneumonia | Community-acquired pneumonia | Sepsis | Aseptic meningitis | Deep vein thrombosis/pulmonary embolism | Erythematous skin rash |
|---|
| CC-4047 Arm | 4 | 12 | 6 | 4 | 2 | 1 | 1 | 1 | 1 | 1 |
Organ System Response
(NCT00770757)
Timeframe: 1 year after last dose of CC-4047
| Intervention | participants (Number) |
|---|
| Skin erythema - complete organ response | Skin erythema - partial organ response | Skin movable sclerosis - complete organ response | Skin movable sclerosis - partial organ response | Mouth - complete organ response | Mouth - partial organ response | Eyes - complete organ response | Eyes - partial organ response | Gastrointestinal - complete organ response | Gastrointestinal - partial organ response |
|---|
| CC-4047 Arm | 2 | 3 | 0 | 1 | 2 | 0 | 1 | 1 | 2 | 0 |
Survival Rate of CC-4047 Responders
(NCT00770757)
Timeframe: Median follow-up 5.6 years (4.2-5.6 years)
| Intervention | percentage of participants (Number) |
|---|
| CC-4047 Arm | 100 |
Phase 2: Time to Response as of the 01 April 2011 Cut-off
"Time to myeloma response is defined as the time from randomization to the time the response criteria for complete response (CR) or partial response (PR) are first met.~Response was assessed by the Independent Response Adjudication Committee (IRAC) using European Group for Blood and Bone Marrow Transplant (EBMT) criteria as described previously.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: up to 70 weeks
| Intervention | weeks (Median) |
|---|
| Phase 2: Pomalidomide + Dexamethasone | 8.1 |
| Phase 2: Pomalidomide | 8.9 |
Phase 2: Kaplan-Meier Estimates of Duration of Response as of the 01 April 2011 Cut-off
"Duration of myeloma response is defined as the time from when the response criteria are first met for partial response (PR) or better, until the first date the response criteria are met for progressive disease (PD) or until the participant dies from any cause, whichever occurs first. Duration of response for participants last known to be alive with no progression after a complete response (CR) or PR was censored at the date of last adequate response assessment. Participants with confirmed responses that occur after receiving any other anti-myeloma therapy (except for adding dexamethasone to the pomalidomide treatment arm), including radiation therapy initiated after baseline, was censored at the last adequate assessment prior to the initiation of such treatment.~Response was assessed by the Independent Response Adjudication Committee (IRAC) using European Group for Blood and Bone Marrow Transplant (EBMT) criteria as described in the previous outcome." (NCT00833833)
Timeframe: up to 70 weeks
| Intervention | weeks (Median) |
|---|
| Phase 2: Pomalidomide + Dexamethasone | 32.1 |
| Phase 2: Pomalidomide | NA |
Phase 2: Kaplan-Meier Estimates of Overall Survival as of the 01 April 2011 Cut-off
"Overall survival was defined as the time between randomization and death. Participants who die, regardless of the cause of the 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 subject was known to be alive, or clinical cut-off date if it was earlier.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: up to 70 weeks
| Intervention | weeks (Median) |
|---|
| Phase 2: Pomalidomide + Dexamethasone | 62.6 |
| Phase 2: Pomalidomide | 59.3 |
Phase 2: Kaplan-Meier Estimates of Progression-free Survival (PFS) as of the 01 April 2011 Cut-off
"Progression free survival (PFS) is the time from randomization to the first documentation of disease progression or death from any cause during study, whichever occurs earlier. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC).~For the primary PFS analysis, participants who withdrew for any reason or received another antimyeloma therapy (except adding dexamethasone to the Phase 2: Pomalidomide arm) without documented PD (as determined by the IRAC review) were censored on the date of their last adequate response assessment, prior to receiving any other anti-myeloma therapy. Subjects who were still active at the time of the data cut-off date without PD (as determined by the IRAC) were censored on the date of their last adequate response assessment.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: up to 67 weeks
| Intervention | weeks (Median) |
|---|
| Phase 2: Pomalidomide + Dexamethasone | 16.6 |
| Phase 2: Pomalidomide | 10.7 |
Phase 2: Percentage of Participants With Progression-Free Survival (PFS) Events as of the 01 April 2011 Cut-off
"Percentage of participants with the progression-free survival events: disease progression and death. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC).~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: up to 67 weeks
| Intervention | percentage of participants (Number) |
|---|
| Phase 2: Pomalidomide + Dexamethasone | 76.1 |
| Phase 2: Pomalidomide | 75.0 |
Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Both Pomalidomide and Dexamethasone as of the 01 April 2011 Cut-off
"TEAEs that occurred during Phase 1 after dexamethasone was added to pomalidomide treatment.~Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. 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.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: Up to week 126
| Intervention | percentage of participants (Number) |
|---|
| 1 or more (1+) AE | 1+ AE related to pomalidomide | 1+ AE related to dexamethasone | 1+ severity grade 3-4 AE | 1+ severity grade 3-4 AE related to pomalidomide | 1+ severity grade 3-4 AE related to dexamethasone | 1+ serious AE (SAE) | 1+ SAE related to pomalidomide | 1+ SAE related to dexamethasone | 1+ AE leading to discontinuation of pomalidomide | 1+ AE -- discontinuation of dexamethasone | 1+AE -dose reduction/interruption of pomalidomide | 1+ AE-dose reduction/interruption of dexamethasone | 1+related AE-reduction/interruption of pomalidomid | 1+related AE-reduction/interruption of dexamethaso |
|---|
| Phase 1: 2 mg Pomalidomide | 100.0 | 100.0 | 100.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
,| Phase 1: 3 mg Pomalidomide | 100.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 75.0 | 25.0 | 50.0 | 25.0 | 25.0 | 50.0 | 75.0 | 25.0 | 75.0 |
,| Phase 1: 4 mg Pomalidomide | 90.0 | 80.0 | 70.0 | 70.0 | 20.0 | 20.0 | 40.0 | 20.0 | 10.0 | 20.0 | 20.0 | 40.0 | 60.0 | 20.0 | 20.0 |
,| Phase 1: 5 mg Pomalidomide | 100.0 | 100.0 | 85.7 | 57.1 | 42.9 | 0.0 | 28.6 | 0.0 | 0.0 | 0.0 | 0.0 | 71.4 | 71.4 | 57.1 | 42.9 |
Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) While on Single-Agent Pomalidomide as of the 01 April 2011 Cut-off
"Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. 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.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: Up to week 104
| Intervention | percentage of participants (Number) |
|---|
| 1 or more (1+) AE | 1+ AE related to pomalidomide | 1+ severity grade 3-4 AE | 1+ severity grade 3-4 AE related to pomalidomide | 1+ serious AE (SAE) | 1+ SAE related to pomalidomide | 1+ AE leading to discontinuation of pomalidomide | 1+AE-dose reduction/interruption of pomalidomide | 1+related AE-reduction/interruption of pomalidomid |
|---|
| Phase 1: 2 mg Pomalidomide | 100.0 | 66.7 | 83.3 | 33.3 | 50.0 | 0.0 | 16.7 | 16.7 | 0.0 |
,| Phase 1: 3 mg Pomalidomide | 100.0 | 75.0 | 37.5 | 25.0 | 12.5 | 12.5 | 0.0 | 75.0 | 37.5 |
,| Phase 1: 4 mg Pomalidomide | 100.0 | 85.7 | 78.6 | 42.9 | 42.9 | 7.1 | 21.4 | 42.9 | 28.6 |
,| Phase 1: 5 mg Pomalidomide | 100.0 | 100.0 | 80.0 | 70.0 | 30.0 | 10.0 | 0.0 | 80.0 | 70.0 |
Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) as of the 01 April 2011 Cut-off
"Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 5= Death related to AE. 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.~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: Up to week 70
| Intervention | percentage of participants (Number) |
|---|
| 1 or more (1+) AE | 1+ AE related to pomalidomide | 1+ severity grade 3-4 AE | 1+ severity grade 3-4 AE related to pomalidomide | 1+ serious AE (SAE) | 1+ SAE related to pomalidomide | 1+ AE leading to discontinuation of pomalidomide | 1+related AE --discontinuation of pomalidomide | 1+AE - reduction of pomalidomide | 1+ AE - interruption of pomalidomide | 1+ related AE - interruption of pomalidomide | 1+related AE - reduction of pomalidomide |
|---|
| Phase 2: Pomalidomide (Overall) | 100.0 | 88.8 | 89.7 | 67.3 | 67.3 | 20.6 | 12.1 | 3.7 | 29.9 | 58.9 | 32.7 | 24.3 |
,| Phase 2: Pomalidomide (Pom + Dex Only) | 93.4 | 68.9 | 70.5 | 44.3 | 47.5 | 19.7 | 3.3 | 1.6 | 9.8 | 36.1 | 21.3 | 8.2 |
,| Phase 2: Pomalidomide (Pom Only) | 99.1 | 87.9 | 84.1 | 58.9 | 46.7 | 9.3 | 10.3 | 2.8 | 25.2 | 47.7 | 24.3 | 20.6 |
,| Phase 2: Pomalidomide + Dexamethasone | 100.0 | 89.3 | 88.4 | 62.5 | 61.6 | 17.9 | 8.0 | 1.8 | 20.5 | 63.4 | 27.7 | 17.9 |
Phase 2: Summary of Best Myeloma Response As Assessed by Independent Response Adjudication Committee (IRAC) Using European Group for Blood and Bone Marrow Transplant (EBMT) Criteria as of the 01 April 2011 Cut-off
"IRAC used EBMT criteria to assess myeloma response:~Complete Response (CR)-absence of serum and urine monoclonal paraprotein for 6 weeks, plus no increase in size or number of lytic bone lesions, plus other factors)~Partial Response (PR)-not all CR criteria, plus >=50% reduction in serum monoclonal paraprotein plus others~Minimal Response (MR)- 25-49% reduction in serum monoclonal paraprotein plus others~Stable Disease (SD)- not MR or progressive disease (PD)~Progressive Disease (PD)- reappearance of monoclonal paraprotein, lytic bone lesions, other~Not Evaluable (NE).~Data collection is ongoing and future data results will be included as available." (NCT00833833)
Timeframe: up to 70 weeks
| Intervention | percentage of participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Minimal response (MR) | Stable disease (SD) | Progressive disease (PD) | Not evaluable |
|---|
| Phase 2: Pomalidomide | 0.0 | 9.3 | 15.7 | 46.3 | 15.7 | 13.0 |
,| Phase 2: Pomalidomide + Dexamethasone | 0.9 | 29.2 | 15.0 | 35.4 | 6.2 | 13.3 |
Phase 1: Participants With Dose-Limiting Toxicities (DLT) in Cycle 1
"The maximum tolerated dose was defined as the highest dose level at which no more than 1 of 6 participants experiences a DLT within the first 28-day cycle.~DLTs were defined as:~Grade 4 neutropenia or thrombocytopenia~Febrile neutropenia~Grade 3 or 4 nausea, vomiting or diarrhea despite optimal symptomatic treatment~Serum transaminase > 20 * upper limit of normal (ULN)~Serum transaminase > 5 * ULN for >= 7 days~Delay of the start of cycle 2 by >7 days due to pomalidomide-related adverse event" (NCT00833833)
Timeframe: Up to Day 28 (Cycle 1)
| Intervention | participants (Number) |
|---|
| Phase 1: 2 mg Pomalidomide | 1 |
| Phase 1: 3 mg Pomalidomide | 1 |
| Phase 1: 4 mg Pomalidomide | 2 |
| Phase 1: 5 mg Pomalidomide | 4 |
Number of Participants With Best Overall Response
Primary endpoint is best overall response. An evaluable subject classified as a treatment success for the primary endpoint if the subject's best overall response is clinical improvement (CI) as determined by International Working Group Criteria over the first 6 cycles of study treatment. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis - Clinical improvement (CI) in anemia 1/ A minimum 20g/L increase in hemoglobin level or 2. becoming transfusion independent for at least 8 week duration. (NCT00946270)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 CC-4047 | 0 |
| Group 2 | 3 |
| Group 3 CC-4047 + Prednisone | 6 |
Maximum Tolerated Dose of Pomalidomide
To determine the MTD of pomalidomide administered orally in patients with Waldenstrom's Macroglobulinemia in combination with dexamethasone and rituximab. Because maximum tolerated dose was not determined due to study termination, the highest dose of pomalidomide administered is presented below. (NCT01078974)
Timeframe: 2 years
| Intervention | mg (Number) |
|---|
| Pomalidomide, Dexamethasone, Rituximab | 1 |
Tolerability of Pomalidomide
Number of participants with dose limiting toxicities which resulted in being removed from pomalidomide therapy (NCT01078974)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Pomalidomide, Dexamethasone, Rituximab | 3 |
Time to Disease Progression (Progression Free Survival)
(NCT01159574)
Timeframe: From start of treatment, to date of disease progression
| Intervention | days (Mean) |
|---|
| All Patients | 272 |
Time to Maximum Response, Expressed as Number of Cycles of Treatment to Maximum Response
(NCT01159574)
Timeframe: From baseline to cycle of maximum response, which occurred on average after 2 cycles; 1 cycle = 28 days
| Intervention | cycles (Mean) |
|---|
| All Patients | 2.19 |
Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy
Progression -free survival (PFS) after initiation of pomalidomide therapy. Progressive disease is defined as increase of > 25% from lowest response value in any 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. (NCT01177735)
Timeframe: 1 year following initiation of pomalidomide therapy
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide | 13 |
Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score
The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire measuring the four general domains of QoL (physical, social/family, emotional and functional well-being), and an additional 20-item anemia questionnaire (FACT-An Anemia subscale) that measures 13 fatigue-associated items (FACT-F Fatigue subscale) and seven non-fatigue-related items. Each item is scored using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 4 = Very much). FACT-An total score is calculated by adding all the FACT-An subscales together. The total score ranges from 0-188 with higher scores representing better QOL. (NCT01178281)
Timeframe: Baseline and Days 85 and 169
| Intervention | units on a scale (Mean) |
|---|
| Day 85 | Day 169 |
|---|
| Placebo | 4.3 | 11.9 |
,| Pomalidomide 0.5 mg | -2.1 | 6.2 |
Change From Baseline in EuroQoL-5D (EQ-5D) Visual Analog Scale
EQ-5D is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D includes 2 components: the EQ-5D health state profile (descriptive system) and the EQ-5D visual analog scale (VAS). On the VAS the participant rates his/her health state on a line from 0 (worst imaginable health) to 100 (best imaginable health). (NCT01178281)
Timeframe: Baseline and Days 85 and 169
| Intervention | units on a scale (Mean) |
|---|
| Day 85 | Day 169 |
|---|
| Placebo | -1.4 | 0.3 |
,| Pomalidomide 0.5 mg | 2.0 | 2.9 |
Change From Baseline in EuroQoL-5D (EQ-5D) Health Index Score
"EQ-5D is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D includes 2 components: the EQ-5D health state profile (descriptive system) and the EQ-5D visual analog scale (VAS). For the health state profile participants rate their perceived health state today on 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression on a Likert-type scale from 1 to 3, where 1 = no problems, 2 = some problems, and 3 = extreme problems. The EQ-5D Health Utility Index (HUI) was generated from the five health state domain scores, and ranges from -0.594 (worst) and 1 (best) imaginable health state, with -0.594 representing an unconscious health state." (NCT01178281)
Timeframe: Baseline and Days 85 and 169
| Intervention | score on a scale (Mean) |
|---|
| Day 85 | Day 169 |
|---|
| Placebo | -0.0298 | 0.0766 |
,| Pomalidomide 0.5 mg | -0.0385 | -0.0202 |
Overall Survival
The time from randomization to the death or to the latest date when participants are known to be alive. Overall survival was analyzed using Kaplan-Meier method; participants who were alive or lost to follow-up were censored at the latest date they were known to be alive. (NCT01178281)
Timeframe: From first dose of study drug up to end of study; median follow-up time was 19.1 months in the pomalidomide 0.5 mg arm and 17.6 months in the placebo arm.
| Intervention | months (Median) |
|---|
| Pomalidomide 0.5 mg | 24.2 |
| Placebo | 26.2 |
Number of Participants With Treatment-emergent Adverse Events (TEAE)
A TEAE is an adverse event (AE) that starts on or after the first dose of study drug. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE),Version 4.0 and according to the following scale: Grade 1 = Mild (transient or mild discomfort; no limitation in activity; no medical intervention/therapy required); Grade 2 = Moderate (mild to moderate limitation in activity, some assistance may be needed; minimal medical intervention/therapy required); Grade 3 = Severe (marked limitation in activity, assistance usually required; medical intervention/therapy required, hospitalization possible); Grade 4 = Life-threatening (extreme limitation in activity, significant assistance or medical intervention/therapy required, hospitalization or hospice care probable); Grade 5 = Death Drug-related (related) AEs are those suspected by the Investigator as being related to administration of study drug (NCT01178281)
Timeframe: From the first dose of study drug until 28 days after last dose; median treatment duration was 23.7 weeks in the pomalidomide arm, 23.9 weeks in the placebo arm, and 24.0 weeks in the China extension pomalidomide arm.
| Intervention | Participants (Count of Participants) |
|---|
| Any adverse event (AE) | Adverse event suspected as related to study drug | Adverse event leading to dose interruption | Drug-related AE leading to dose interruption | AE leading to discontinuation of study drug | Related AE leading to study drug discontinuation | Grade 3/4 adverse event | Grade 3/4 AE related to study drug | Grade 3/4 AE leading to study drug discontinuation | Grade 3/4 AE leading to dose interruption | Grade 5 adverse event | Grade 5 AE related to study drug | Serious adverse event (SAE) | SAE related to study drug | SAE leading to discontinuation of study drug | SAE leading to dose interruption |
|---|
| China Extension: Pomalidomide 0.5 mg | 12 | 3 | 2 | 1 | 0 | 0 | 4 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Placebo | 81 | 32 | 17 | 6 | 14 | 8 | 44 | 13 | 9 | 14 | 10 | 3 | 29 | 7 | 8 | 7 |
,| Pomalidomide 0.5 mg | 164 | 90 | 48 | 26 | 53 | 21 | 100 | 45 | 33 | 36 | 17 | 1 | 76 | 24 | 31 | 22 |
Percentage of Participants Who Achieved RBC-Transfusion Independence
RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval. (NCT01178281)
Timeframe: 168 days
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide 0.5 mg | 17.3 |
| Placebo | 16.7 |
Time to RBC-Transfusion Independence
Time to response was measured from first dose of study drug to the start of the first response. The start date of the response was defined as one day after the last date of an RBC-transfusion for participants who received a RBC-transfusion after the first dose, and as the date of the first dose of study drug for participants who received no RBC-transfusions during the 84 days after the first dose of study drug. (NCT01178281)
Timeframe: 168 days
| Intervention | weeks (Median) |
|---|
| Pomalidomide 0.5 mg | 6.9 |
| Placebo | 2.4 |
China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days
A response in the China extension study was defined as an increase in hemoglobin ≥ 15 g/L above baseline value (in the absence of RBC transfusion) for ≥ 84 consecutive days. (NCT01178281)
Timeframe: From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks.
| Intervention | Participants (Count of Participants) |
|---|
| China Extension: Pomalidomide 0.5 mg | 1 |
Duration of RBC-Transfusion Independence
The duration of RBC-transfusion independence is the time from the date at which the first RBC-transfusion independence started to the date of another RBC-transfusion given at least 84 days after the time the transfusion independence started. The duration of the RBC-transfusion independence was analyzed using the Kaplan-Meier method. Data were censored at the end of the treatment phase for participants who had not received another RBC-transfusion after the start of transfusion independence by the end of treatment phase. (NCT01178281)
Timeframe: From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.
| Intervention | months (Median) |
|---|
| Pomalidomide 0.5 mg | NA |
| Placebo | 5.8 |
Progression Free Survival
The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. PD: Increase of > 25% from lowest response value in any 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) (NCT01212952)
Timeframe: 2.5 years
| Intervention | months (Median) |
|---|
| Phase I - Dose Level 1 | 13.9 |
| Phase I - Dose Level 2 | 18.1 |
| Phase II | 10.7 |
Number of Participants With Adverse Events
Reported in Adverse Events section of the results (NCT01212952)
Timeframe: 2.5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase I - Dose Level 1 | 3 |
| Phase I - Dose Level 2 | 6 |
| Phase II | 41 |
Find Maximum Tolerated Dose (MTD) of Bortezomib in Combination With Pomalidomide and Dexamethasone Out to 2.5 Years, by Count of Patients With Dose Limiting Toxicities.
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). (NCT01212952)
Timeframe: 2.5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Level 1 | 0 |
| Phase 1 Dose Level 2 | 1 |
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 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 |
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 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 |
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 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 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 |
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 |
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 |
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 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 |
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 |
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 |
Progression-free Survival (PFS) - Primary Analysis
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 15.7 |
| High-Dose Dexamethasone | 8.0 |
Duration of Response
Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 35.1 |
| High-Dose Dexamethasone | 28.1 |
Overall Survival - Primary Analysis
Overall survival is calculated 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | NA |
| High-Dose Dexamethasone | 34.0 |
Overall Survival Based on the Final Dataset
Overall survival is calculated 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 29 August 2017. Maximum time on follow-up for survival was 324 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 56.1 |
| High-Dose Dexamethasone | 35.3 |
Overall Survival With a Later Cut-off Date
Overall survival is calculated 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 54.0 |
| High-Dose Dexamethasone | 34.9 |
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 22.2 |
| High-Dose Dexamethasone | 3.3 |
Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms
The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms. (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | -1.07 | 0.97 | 1.35 | 1.48 | 2.12 |
,| Pomalidomide Plus Low-Dose Dexamethasone | -0.50 | -1.36 | -1.15 | -0.53 | 0.60 |
Change From Baseline in the European Organization for Research and Treatment of Cancer 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. (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | -3.75 | -2.36 | -3.03 | 0.00 | -0.93 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 0.52 | 2.67 | 0.80 | 0.51 | -2.51 |
Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom). (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | 2.61 | 5.35 | 7.46 | 6.89 | 7.30 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 2.71 | 3.26 | 3.73 | 4.74 | 4.55 |
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. (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | -3.96 | -9.69 | -8.08 | -5.43 | -4.81 |
,| Pomalidomide Plus Low-Dose Dexamethasone | -2.32 | -0.56 | 0.17 | 0.91 | 0.54 |
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 reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom). (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | 0.36 | 2.83 | 3.03 | 2.47 | 10.19 |
,| Pomalidomide Plus Low-Dose Dexamethasone | -2.70 | -3.58 | -2.41 | -1.64 | -2.40 |
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 reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom). (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | 4.03 | 7.76 | 9.43 | 9.47 | 10.49 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 2.43 | 3.26 | 1.71 | 0.21 | 0.99 |
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
"EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). 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 an EQ-5D score of 1.00 equals perfect health, a score of 0 equals death and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL" (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | -0.02 | -0.06 | -0.07 | -0.04 | -0.12 |
,| Pomalidomide Plus Low-Dose Dexamethasone | -0.03 | 0.01 | 0.04 | 0.01 | 0.03 |
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. (NCT01311687)
Timeframe: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
| Intervention | units on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5 Day 1 | Cycle 6, Day 1 |
|---|
| High-Dose Dexamethasone | -2.87 | -5.66 | -6.31 | -8.64 | -4.17 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 1.22 | 2.40 | 2.44 | 1.91 | 0.19 |
Time to the First Hemoglobin Improvement
Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: < lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: < 10.0 to <8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 3.4 |
| High-Dose Dexamethasone | 1.3 |
Number of Participants With Adverse Events (AEs)
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. (NCT01311687)
Timeframe: From first dose of study drug through to 30 days after the last dose as of the end of the study (29 August 2017); maximum time on treatment was 297, 269, and 239 weeks in the Pomalidomide + LD-Dex, HD-Dex, and cross-over groups respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Any adverse event | Grade 3-4 adverse events | AE related to pomalidomide | AE related to dexamethasone | AE related to either study drug | Grade 3-4 AE related to pomalidomide | Grade 3-4 AE related to dexamethasone | Grade 3-4 AE related to either study drug | Grade 5 adverse events | Serious adverse events (SAEs) | SAE related to pomalidomide | SAE related to dexamethasone | SAE related to either study drug | SAE leading to discontinuation of pomalidomide | SAE leading to discontinuation of dexamethasone | SAE leading to discontinuation of either study dru | AE leading to discontinuation of pomalidomide | AE leading to discontinuation of dexamethasone | AE leading to discontinuation of either study drug |
|---|
| HD-Dex / Pomalidomide | 11 | 8 | 11 | 5 | 11 | 6 | 2 | 6 | 1 | 4 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
,| High-Dose Dexamethasone | 149 | 127 | 0 | 115 | 115 | 0 | 70 | 70 | 21 | 80 | 0 | 36 | 36 | 0 | 14 | 14 | 0 | 16 | 16 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 298 | 266 | 251 | 205 | 271 | 199 | 114 | 212 | 46 | 195 | 89 | 73 | 98 | 20 | 20 | 23 | 30 | 34 | 38 |
Time to Progression
Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 20.0 |
| High-Dose Dexamethasone | 9.0 |
Time to Improvement in Renal Function
Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to <80 mL/min; - Grade 2 : creatinine clearance ≥45 to < 60 mL/min. Participants with creatinine clearance < 45 mL/min at baseline were excluded from the study. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 4.6 |
| High-Dose Dexamethasone | 4.1 |
Time to Improvement in Bone Pain
"Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, Have you had bone aches or pain?: 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much." (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 5.7 |
| High-Dose Dexamethasone | 4.1 |
Time to Response
Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG 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. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 8.1 |
| High-Dose Dexamethasone | 10.5 |
Time to First Worsening of Quality of Life (QOL) Domains
Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale. (NCT01311687)
Timeframe: Assessed on Day 1 of the first 6 treatment cycles.
| Intervention | days (Median) |
|---|
| Global Health Status | Physical Functioning | Emotional Functioning | Fatigue | Pain | Disease Symptoms | Side Effects of Treatment | Health Utility |
|---|
| High-Dose Dexamethasone | 57 | 67 | 85 | 57 | 85 | 106 | 85 | 162 |
,| Pomalidomide Plus Low-Dose Dexamethasone | 71 | 128 | 146 | 58 | 92 | 127 | 90 | 225 |
Progression-free Survival (PFS) With a Later Cut-off Date
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • 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. (NCT01311687)
Timeframe: From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Low-Dose Dexamethasone | 16.0 |
| High-Dose Dexamethasone | 8.1 |
Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria
All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart. (NCT01319422)
Timeframe: Efficacy assessments will be made after the first two cycles of therapy (approximately 56 days--each cycle is 28 days)
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide 2 mg/d on 28 Days/28 Day Cycle | 15.8 |
| Pomalidomide 4 mg/d on 21 Days/28 Day Cycle | 20.0 |
Percentage of Participants With Response, Analyzed Per International Myeloma Working Group Response Criteria
All partial and complete responses must be confirmed with another efficacy assessment in no less than 4 weeks apart. (NCT01319422)
Timeframe: After the initial efficacy assessment at the completion of cycle 2 (at approximately 56 days), efficacy assessments will be made after every other cycle (approximately every 56 days).
| Intervention | percentage of participants (Number) |
|---|
| cycle 4 | cycle 6 | cycle 8 | cycle 10 | cycle 12 | cycle 14 |
|---|
| Pomalidomide 2 mg/d on 28 Days/28 Day Cycle | 15.8 | 21.0 | 21.0 | 21.0 | 21.0 | 21.0 |
,| Pomalidomide 4 mg/d on 21 Days/28 Day Cycle | 40.0 | 40.0 | 45.0 | 45.0 | 45.0 | 45.0 |
Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria
Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria. (NCT01324947)
Timeframe: From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum duration of response follow-up was 90.3 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide | 28.3 |
Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria
"Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG).~Progressive disease 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 > 100 mg/dl)~Bone marrow plasma cell percentage (absolute % ≥ 10%)~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." (NCT01324947)
Timeframe: From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to progression follow-up was 90.3 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide | 19.0 |
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment
"Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following:~Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days.~<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed.~No increase in size or number of lytic bone lesions.~Disappearance of soft tissue plasmacytomas.~PR requires all of the following:~≥50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days.~Reduction in 24-hour urinary light chain extraction by ≥90% or to <200 mg, maintained at least 42 days.~For patients with non-secretory myeloma, ≥50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days." (NCT01324947)
Timeframe: From randomization through the study follow-up phase; up to the data cut-off of 31 July 2014; Maximum time on follow-up was 141.1 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide | 20.3 |
Time to Response Based on IMWG and Assessed by the Investigator
Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator. (NCT01324947)
Timeframe: From randomization through the follow-up phase; up to the data-cut off of 31 July 2014; Maximum time to response was 23.1 weeks
| Intervention | weeks (Median) |
|---|
| Pomalidomide | 8.3 |
Kaplan-Meier Estimate for Overall Survival
Overall survival was calculated 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. (NCT01324947)
Timeframe: From randomization through the follow-up phase; Maximum time on follow-up was 141.1 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide | 33.6 |
Number of Participants With Adverse Events and Type of 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" (NCT01324947)
Timeframe: From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 31 July 2014. Maximum time on treatment was 94.1 weeks.
| Intervention | participants (Number) |
|---|
| Any adverse event | Grade 3-4 adverse event | AE related to pomalidomide | Grade 3-4 AE related to pomalidomide | Grade 5 AE | ≥1 Serious AE (SAE) | ≥1 SAE related to pomalidomide | ≥1 SAE leading to stopping pomalidomide | ≥AE leading to discontinuation of pomalidomide | ≥1 study drug related AE leading to stopping POM | ≥1 AE leading to reduction of pomalidomide | ≥1 study drug related AE leading to reducing POM | ≥1 AE leading to interruption of pomalidomide | ≥ 1 study drug related interruption of POM |
|---|
| Pomalidomide | 73 | 64 | 51 | 33 | 19 | 52 | 15 | 6 | 8 | 1 | 11 | 9 | 41 | 25 |
Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG
"Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier.~Progressive disease 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 > 100 mg/dl)~Bone marrow plasma cell percentage (absolute % ≥ 10%)~Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas." (NCT01324947)
Timeframe: From randomization through the follow-up phase; Maximum duration of follow-up for PFS was 90.3 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide | 16.0 |
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 |
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 |
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 |
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 |
Phase II - Overall Response Rate (ORR)
Overall response, Minimal Remission (MR) or better per treatment arm, using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in participants with relapsed and refractory myeloma. In addition, Minimal response was incorporated in those response criteria as this is a valid endpoint in patients with relapsed or refractory myeloma. MR: 25-49% reduction in serum paraprotein and a 50-89% reduction in urine light chain excretion; A 25-49% reduction in the size of soft tissue plasmacytoma must be demonstrated is applicable. (NCT01432600)
Timeframe: 36 Months
| Intervention | percentage of participants (Number) |
|---|
| B: Pomalidomide and Dexamethasone | 38.9 |
| C: Pomalidomide, Dexamethasone, Cyclophosphamide | 64.7 |
Phase I - Maximum Tolerated Dose (MTD)
The maximum tolerated dose of oral weekly cyclophosphamide in milligrams (mg), in combination with pomalidomide and dexamethasone. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. The period for assessment of Dose Limiting Toxicity (DLT) is the first cycle (28 days). The following toxicities will be considered dose limiting if encountered only in the phase I portion of the study: Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity related to treatment with pomalidomide or cyclophosphamide; Participants must have received optimal symptomatic treatment for Grade 3 or 4 nausea, vomiting, or diarrhea to be considered a DLT; Grade 4 transaminitis; Grade 3 transaminitis must be present for ≥ 7 days to be considered a DLT; Grade 4 thrombocytopenia for 7 or more days; Grade 4 neutropenia for 7 or more days. (NCT01432600)
Timeframe: 28 Days
| Intervention | mg (Number) |
|---|
| A: Dose Escalation of Cyclophosphamide | 400 |
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. (NCT01495598)
Timeframe: Date treatment consent signed to date off study, approximately 124 months and 1 day.
| Intervention | Participants (Count of Participants) |
|---|
| All Participants - Pomalidomide 5mg Daily | 28 |
Area Under the Plasma Concentration Versus Time Curve (AUC) to the Last Timepoint (AUCLast)
Area under the plasma concentration versus time curve (AUC) was calculated using the log-linear trapezoidal method. The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. (NCT01495598)
Timeframe: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
| Intervention | hours*ng/mL (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| All Participants - Pomalidomide 5mg Daily | 466.5 | 504.5 |
Change Between Timepoints Baseline to 4 Weeks, Baseline to 8 Weeks, and Baseline to End of Treatment in Kaposi Sarcoma-Associated Herpesvirus (KSHV) Viral Load
KSHV viral load in peripheral blood mononuclear cells was assessed by modifying a sandwich enzyme-linked immunosorbent assay (ELISA). Viral load testing may provide useful information on the occurrence of KSHV replication. Undetectable levels is good. (NCT01495598)
Timeframe: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
| Intervention | copies per million PBMC (Median) |
|---|
| Baseline to 4 Weeks | 0 |
| Baseline to 8 Weeks | 0 |
| Baseline to End of Treatment | 0 |
Human Immunodeficiency Virus (HIV) Viral Load
HIV viral load in peripheral blood mononuclear cells was assessed by quantitative real-time polymerase chain reaction (PCR). The lower limit of detection for HIV viral load is <50 copies mL. (NCT01495598)
Timeframe: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
| Intervention | Copies/mL (Median) |
|---|
| Baseline to 4 Weeks | 0 |
| Baseline to 8 Weeks | 0 |
| Baseline to End of Treatment | 0 |
Number of Dose-limiting Toxicities
"A dose limiting toxicity is any grade 4 toxicity not including lymphopenia, cluster of differentiation 4 (CD4) lymphopenia, neutropenia, anemia and bilirubin or creatine kinase (CK) elevation that is at least possibly due to pomalidomide and is not attributable to human immunodeficiency virus (HIV), its therapy or Kaposi Sarcoma (KS). Any grade 3 toxicity that is at least possibly due to pomalidomide and is not attributable to HIV, its therapy, or KS and restrictions such as grade 3 thrombocytopenia if grade 3 for 14 days or more, Grade 3 asymptomatic hyperuricemia or hypophosphatemia, or Grade 3 amylase elevations.~Any arterial or deep venous thromboembolic event or a second superficial thromboembolic event that is at least possibly due to pomalidomide. Inability to deliver pomalidomide on at least 50% of scheduled days during the first two cycles of therapy as a result of toxicity that is probably or definitely attributable to pomalidomide." (NCT01495598)
Timeframe: First 8 weeks (2 cycles) of drug administration
| Intervention | toxicities (Number) |
|---|
| All Participants - Pomalidomide 5mg Daily | 0 |
Change in Cytokines From Baseline to 4 Weeks, Baseline to 8 Weeks and End of Treatment
Cytokines were evaluated using MSD 96-Well Multiarray Proinflammatory 7-plex assay (MesoScale Discovery). (NCT01495598)
Timeframe: Baseline to 4 weeks, baseline to 8 weeks and baseline to end of treatment
| Intervention | pg/mL (Median) |
|---|
| Interferon gamma (ƴ) | Interleukin 4 (IL4) | Interleukin 6 (IL6) | Interleukin 8 (IL8) | Interleukin 10 (IL10) | Interleukin 12 (IL12) | Interleukin 13 (IL13) | Tumor necrosis factor alpha (TNFα) | Interferon (IFN)-inducible protein 10 (IP-10) |
|---|
| Baseline to 4 Weeks | -0.3 | 0.07 | 0.4 | 71.9 | 0.1 | 0.02 | 0.7 | 0.3 | 76.5 |
,| Baseline to 8 Weeks | -0.4 | 0.1 | 0.3 | 64.8 | -0.03 | 0.00 | 0.9 | 0.5 | 18.4 |
,| Baseline to End of Treatment | -2.4 | 0.06 | 0.6 | 47.5 | -0.05 | 0.03 | 0.6 | 0.06 | -73.3 |
Progression Free Survival (PFS)
PFS is defined as time from day 1 of pomalidomide therapy until progression requiring a change in therapy, estimated using the Kaplan-Meier method. Progression was assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions. (NCT01495598)
Timeframe: time from day 1 of pomalidomide therapy until progression requiring a change in therapy, an average of 9.97 months
| Intervention | months (Median) |
|---|
| All Participants | 10.2 |
| HIV Positive Participants | 10.3 |
| HIV Negative Participants | 9.4 |
Antitumor Effect of a First Course of Pomalidomide
Antitumor effect of pomalidomide was assessed at the established tolerated dose after a first course of pomalidomide. Kaposi sarcoma responses were assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Complete Response (CR) required clinical resolution of all lesions and tumor-associated phenomenon with biopsy confirmation. Clinical Complete Response (cCR) is resolution of all lesions except for some residual pigmentation but who did not have a biopsy of a representative pigmented area. Partial Response (PR) required ≥ 50% decrease in the number of lesions and/or sum product of the diameters of marker lesions and/or nodularity of lesions, and no new lesions in previously uninvolved areas or criteria. Stable Disease (SD) was assessed for all participants who did not meet criteria doe CR, PR, or PD. And progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions. (NCT01495598)
Timeframe: After completion of 2 cycles of therapy up to 48 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Clinical Complete Response (CCR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) |
|---|
| All Participants - Pomalidomide 5mg Daily | 1 | 3 | 16 | 5 | 3 |
Antitumor Effect of a Second Course of Pomalidomide
Antitumor effect of pomalidomide was assessed at the established tolerated dose after a second course of pomalidomide. Kaposi sarcoma responses were assessed using the Modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group criteria. Complete Response (CR) required clinical resolution of all lesions and tumor-associated phenomenon with biopsy confirmation. Clinical Complete Response (cCR) is resolution of all lesions except for some residual pigmentation but who did not have a biopsy of a representative pigmented area. Partial Response (PR) required ≥ 50% decrease in the number of lesions and/or sum product of the diameters of marker lesions and/or nodularity of lesions, and no new lesions in previously uninvolved areas or criteria. Stable Disease (SD) was assessed for all participants who did not meet criteria doe CR, PR, or PD. And progressive disease (PD) involved a 25% or greater increase in total lesions, nodular lesion, or area of the five indicator lesions. (NCT01495598)
Timeframe: After completion of 2 cycles of therapy up to 48 weeks after the start of the second course of Pomalidomide
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Clinical Complete Response (CCR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) |
|---|
| All Participants - Pomalidomide 5mg Daily | 0 | 0 | 2 | 2 | 0 |
Area Under the Curve Extrapolated to Infinity (AUCinf)
AUC is a measure of the serum concentration of Pomalidomide over time. It is used to characterize drug absorption. The AUC extrapolated to infinity was used, unless the percent extrapolated exceeded 25% in which case AUC to the last quantifiable time point (AUCLast) was used. The steady-state exposure on Day 15 of cycle 1 was calculated using AUCLast. (NCT01495598)
Timeframe: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
| Intervention | hours*ng/ml (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| All Participants - Pomalidomide 5mg Daily | 567.3 | 805.3 |
Time to Maximum Observed Serum Concentration of Pomalidomide (Cmax)
Time to maximum observed serum concentration of Pomalidomide was reported. (NCT01495598)
Timeframe: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
| Intervention | hours (Median) |
|---|
| Cycle 1 Day 1 | Cycle 1 day 15 |
|---|
| All Participants - Pomalidomide 5mg Daily | 2.00 | 2.08 |
Number of Participants With Grades 1-4 Adverse Events That Are Possibly, Probably, and/or Definitely Attributed to Pomalidomide
Adverse events (AE's) that are possibly, probably, and/or definitely attributed to pomalidomide were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. (NCT01495598)
Timeframe: During each cycle and 4 weeks after completing therapy, with any continuing AE's observed until resolution, approximately 124 months and 1 day.
| Intervention | Participants (Count of Participants) |
|---|
| Low white cell count | Febrile neutropenia | Neutropenia | Lymphocytopenia | Anemia | Thrombocytopenia | Fatigue | Infection | Constipation | Nausea | Elevated alanine aminotransferase (ALT) | Impaired concentration | Depression | Hypothyroidism | Rash | Vasculitis |
|---|
| Grade 1 | 21 | 0 | 24 | 13 | 16 | 16 | 17 | 0 | 18 | 10 | 7 | 3 | 1 | 3 | 18 | 0 |
,| Grade 2 | 10 | 0 | 26 | 2 | 4 | 0 | 2 | 7 | 3 | 0 | 0 | 1 | 1 | 3 | 6 | 0 |
,| Grade 3 | 1 | 1 | 14 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
,| Grade 4 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Maximal Plasma Concentration (Cmax) of Pomalidomide
Plasma concentrations of pomalidomide were assayed using high-performance liquid chromatography with fluorescence detection with a lower limit of quantitation of 1 ng/mL and were recorded as observed values. A non-compartmental analysis was used to calculate plasma pharmacokinetic parameters (Pharsight, Mountain View, California). (NCT01495598)
Timeframe: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| All Participants - Pomalidomide 5mg Daily | 53.1 | 59.0 |
Half-Life of Pomalidomide
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half. (NCT01495598)
Timeframe: At pre-dose, 1, 2, 3, 4, 6, and 8 hours after dose on Cycle 1 Day 1, and pre-dose, 1, 2, 3, 4, 6, 8, and 24 hours after dose on Cycle 1 Day 15.
| Intervention | hours (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 |
|---|
| All Participants - Pomalidomide 5mg Daily | 6.85 | 8.27 |
Change in Immune Cytokines Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Cluster of Differentiation 19 (CD19) Among Participants With and/or Without Human Immunodeficiency Virus (HIV)
Fluorescence activated cell sorting. (NCT01495598)
Timeframe: Baseline to 4 weeks, baseline to 8 weeks, and baseline to end of treatment
| Intervention | cells/µL (Median) |
|---|
| CD4+/All participants | CD4+ among HIV+ participants | CD8+/All participants | CD8+ among HIV+ participants | CD19+/All participants |
|---|
| Baseline to 4 Weeks | 66.5 | 72 | 104.5 | 198 | -40 |
,| Baseline to 8 Weeks | 37 | 37 | 115 | 129 | -55 |
,| Baseline to End of Treatment | -54 | -14 | 73 | 75 | -75 |
Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The social functioning subscale score is calculated as the average of six questions about how often symptoms interfered with social activities; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.3 | 0.1 | 0.0 | 0.0 | 0.2 | 0.0 |
,| Pomalidomide | 0.0 | -0.1 | 0.2 | 0.3 | 0.0 | -0.2 |
Change From Baseline in Dyspnea Magnitude of Task at Week 76
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 76
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Task at Week 64
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 64
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 2 | 3 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 52 or at the Treatment Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 8 | 2 | 0 | 1 | 0 |
,| Pomalidomide | 0 | 3 | 1 | 6 | 0 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carry very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 156 or the Extension Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 1 | 1 | 2 | 2 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Task at Week 12
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 12
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 2 | 5 | 3 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 1 | 5 | 1 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 76
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 76
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 64
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 64
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 3 | 2 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 52 or at the Treatment Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 7 | 3 | 1 | 0 | 0 |
,| Pomalidomide | 0 | 3 | 1 | 6 | 0 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Task at Week 24
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain. (NCT01559129)
Timeframe: Week 24
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 1 | 2 | 5 | 2 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 1 | 1 | 2 | 3 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Functional Impairment at Week 76
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 76
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Change From Baseline in University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Total Score at Week 52/Early Termination
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets gastrointestinal (GI) activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health (except for Questions 15 and 31 which are scored as 0 (better health) or 1 (worse health). The total score is calculated as the average of the first 6 scale scores (excluding constipation) which captures overall burden (severity) of SSc-associated GIT. The overall score ranges from 0 to 3, where higher scores indicate more severe symptoms. (NCT01559129)
Timeframe: Baseline and Week 52 (or Treatment Phase Early Termination visit)
| Intervention | units on a scale (Mean) |
|---|
| Placebo | 0.00 |
| Pomalidomide | 0.1 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 156 or at the Extension Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 1 | 2 | 2 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Functional Impairment at Week 64
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 64
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 4 | 1 | 0 | 0 | 0 |
,| Pomalidomide | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination
Improvement in skin thickening is associated with improved survival and may be useful as a surrogate measurement in clinical studies. The mRSS is an assessment tool which is used to evaluate the extent and severity of the skin thickening associated with systemic sclerosis (SSc). Seventeen body areas were evaluated on a 4-point scale (0 [normal], 1 [mild], 2 [moderate]), or 3 [severe]). The total score, which is the sum of the 17 individual body assessments, can range from 0 to 51. (NCT01559129)
Timeframe: Baseline and Week 52 (or the Treatment Phase Early Termination visit)
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -3.7 |
| Pomalidomide | -2.7 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 24
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 24
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 1 | 0 | 1 | 4 | 3 | 1 | 0 | 0 |
,| Pomalidomide | 1 | 1 | 0 | 3 | 2 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Magnitude of Effort at Week 12
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 12
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 1 | 2 | 4 | 2 | 1 | 0 | 0 |
,| Pomalidomide | 0 | 0 | 2 | 4 | 1 | 0 | 0 | 0 |
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
Forced vital capacity (FVC) is a pulmonary function test and is the volume of air in the lungs that can forcibly be blown out after a full inhalation. Percent predicted values are based comparison between the participant's measured value with expected FVC for someone of the same sex, age and height (reference value). For the analysis of FVC, the baseline value was defined as the average of all values between Screening and Baseline (inclusive), and the average of Weeks 48 and 52 was treated as the Week 52 value, to reduce the total data variability at the key time points. (NCT01559129)
Timeframe: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 52
| Intervention | percent predicted (Mean) |
|---|
| Placebo | -2.8 |
| Pomalidomide | -5.2 |
Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 52 or at the Treatment Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 1 | 8 | 3 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 4 | 1 | 4 | 1 | 0 | 0 | 0 |
Change From Baseline in Dyspnea Functional Impairment at Week 24
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 24
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 1 | 0 | 1 | 4 | 3 | 1 | 0 | 0 |
,| Pomalidomide | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 1 |
Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 156 or the Extension Phase Early Termination visit
| Intervention | Participants (Number) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 0 | 2 | 2 | 1 | 1 | 0 | 0 |
,| Pomalidomide | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The distension/bloating subscale score is calculated as the average of four distension/bloating-related questions; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.4 | 0.0 | 0.0 | -0.2 | 0.0 | -0.3 |
,| Pomalidomide | 0.2 | 0.3 | 0.2 | 1.0 | 3.0 | 0.9 |
Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The emotional well-being subscale score is calculated as the average of nine questions regarding the impact of bowel problems on emotional status; the score ranges from 0 to 3, where higher scores indicate more frequent problems. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.2 | 0.1 | 0.1 | 0.0 | 0.0 | -0.1 |
,| Pomalidomide | -0.4 | -0.3 | -0.1 | 0.2 | 0.3 | 0.0 |
Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The fecal soilage subscale score is calculated from one soilage question; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.0 | 0.2 | 0.0 | 0.2 | 0.0 | 0.2 |
,| Pomalidomide | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 |
Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The reflux subscale score is calculated as the average of eight reflux-related questions; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.1 | -0.1 | -0.1 | -0.2 | -0.5 | 0.0 |
,| Pomalidomide | -0.1 | 0.0 | 0.1 | 0.2 | -0.2 | 0.1 |
Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health (except for Questions 15 and 31 which are scored as 0 (better health) or 1 (worse health). The total score is calculated as the average of the first 6 scale scores (excluding constipation) which captures overall burden (severity) of SSc-associated GIT. The overall score ranges from 0 to 3, where higher scores indicate more severe symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.2 | 0.1 | 0.0 | -0.1 | 0.0 |
,| Pomalidomide | -0.1 | -0.1 | 0.4 | 0.5 | 0.0 |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE is any AE that began or worsened on or after the start of study drug through 28 days after the last dose. A treatment-related TEAE is a TEAE which was considered by the investigator to be related to study drug. The severity/intensity of AEs was assessed by the investigator as Mild (asymptomatic or mild symptoms; intervention not indicated), Moderate (symptoms cause moderate discomfort, intervention may be required), or Severe (symptoms cause severe discomfort/pain, requiring medical intervention, inability to perform daily activities). A serious AE is any AE that: - Resulted in death; - Was life-threatening; - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Constituted an important medical event. (NCT01559129)
Timeframe: From the start of study drug to 28 days after last dose; Treatment Phase median duration of treatment was 358 and 320 days for Placebo and Pomalidomide; Extension phase median duration of treatment was 161 days and 194 days for Placebo and pomalidomide.
| Intervention | participants (Number) |
|---|
| Any TEAE | Drug-related TEAE | Severe TEAE | Serious TEAE | Serious Drug-related TEAE | TEAE Leading to Drug Interruption | TEAE Leading to Drug Withdrawal | TEAE Leading to Death |
|---|
| Extension Phase: Placebo/Pomalidomide | 5 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Extension Phase: Pomalidomide/Pomalidomide | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
,| Treatment Phase: Placebo | 12 | 8 | 1 | 1 | 0 | 2 | 0 | 0 |
,| Treatment Phase: Pomalidomide | 9 | 6 | 4 | 4 | 1 | 1 | 4 | 0 |
Oxygen Saturation Over Time
Oxygen saturation was measured by pulse oximetry. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | percent saturation (Mean) |
|---|
| Baseline | Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 97.5 | 97.1 | 97.6 | 96.8 | 96.3 | 98.5 | 95.8 |
,| Pomalidomide | 96.8 | 97.4 | 96.5 | 96.8 | 94.0 | 97.0 | 97.5 |
Change From Baseline in Dyspnea Functional Impairment at Week 12
The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath. (NCT01559129)
Timeframe: Week 12
| Intervention | Participants (Count of Participants) |
|---|
| Major deterioration | Moderate deterioration | Minor deterioration | No change | Minor improvement | Moderate improvement | Major improvement | Further impairment for other reasons |
|---|
| Placebo | 0 | 1 | 0 | 7 | 2 | 0 | 0 | 0 |
,| Pomalidomide | 0 | 1 | 1 | 3 | 1 | 0 | 0 | 1 |
Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The diarrhea subscale score is calculated as the average of one diarrhea question about the frequency of loose stools (on a scale from 0 [none] to 3 [5-7 days/week] and one question about the presence of watery stools (scored as 0 [No] or 1 [Yes]); the score ranges from 0 to 2, where a higher score indicates more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | 0.4 | 0.1 | 0.3 | 0.1 | 0.0 | 0.3 |
,| Pomalidomide | -0.2 | -0.3 | 0.0 | 0.5 | -0.5 | -0.8 |
Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time
The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets GI activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health. The constipation subscale score is calculated as the average of three questions regarding the frequency of constipation (scored from 0 [no days] to 3 [5-7 days/week] and one question about the presence of stools becoming harder (scored as 0 [No] or 1 [Yes]); the score ranges from 0 to 2.5, where higher scores indicate more frequent symptoms. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 52/Early Termination | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | -0.1 | -0.2 | 0.0 | 0.0 | 0.0 | -0.2 |
,| Pomalidomide | 0.2 | 0.3 | 0.3 | 0.1 | 0.0 | 0.1 |
Change From Baseline in Percent Predicted Forced Vital Capacity Over Time
Forced vital capacity (FVC) is a pulmonary function test and is the volume of air in the lungs that can forcibly be blown out after a full inhalation. Percent predicted values are based comparison between the participant's measured value with expected FVC for someone of the same sex, age and height (reference value). (NCT01559129)
Timeframe: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156
| Intervention | percent predicted (Mean) |
|---|
| Week 12 | Week 24 | Week 36 | Week 64 | Week 76 | Week 156 |
|---|
| Placebo | -2.4 | -1.3 | -2.6 | -7.0 | -8.7 | -6.7 |
,| Pomalidomide | -1.8 | 2.3 | -4.4 | -6.4 | -5.2 | -5.9 |
Change From Baseline in Modified Rodnan Skin Score Over Time
Improvement in skin thickening is associated with improved survival and may be useful as a surrogate measurement in clinical studies. The mRSS is an assessment tool which is used to evaluate the extent and severity of the skin thickening associated with systemic sclerosis (SSc). Seventeen body areas were evaluated on a 4-point scale (0 [normal], 1 [mild], 2 [moderate], or 3 [severe]). The total score, which is the sum of the 17 individual body assessments, can range from 0 to 51. (NCT01559129)
Timeframe: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
| Intervention | units on a scale (Mean) |
|---|
| Week 12 | Week 24 | Week 64 | Week 76 | Week 156/Early Termination |
|---|
| Placebo | -1.8 | -3.6 | -4.3 | -8.5 | -3.7 |
,| Pomalidomide | -0.3 | -2.0 | -4.0 | -7.0 | -4.5 |
Response to the Maximal Tolerated Dose
Number of participants with a response to treatment at that maximal tolerated dose (including partial, very good, or complete responses) (NCT01570387)
Timeframe: one year
| Intervention | Participants (Count of Participants) |
|---|
| Pom Plus Dex | 10 |
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 3 Milligram Dose
Number of patients in Phase I cohort 2 experiencing dose limiting toxicity in the 3 milligram dose level, cohort 2. (NCT01570387)
Timeframe: One month
| Intervention | Participants (Count of Participants) |
|---|
| Pom Plus Dex | 0 |
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 4 Milligram Dose
Number of patients in Phase I cohort 3 experiencing dose-limiting toxicity at the 4 milligram dose for participants within the third dose cohort (NCT01570387)
Timeframe: One month
| Intervention | Participants (Count of Participants) |
|---|
| Pom Plus Dex | 1 |
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 2 Milligram Dose
Number of patients in Phase I cohort 1 experiencing dose-limiting toxicity at the 2 milligram dose of pomalidomide combined with dexamethasone in subjects with previously- treated light-chain amyloidosis (NCT01570387)
Timeframe: one month
| Intervention | Participants (Count of Participants) |
|---|
| Pom Plus Dex | 0 |
Best Overall Response - Multiple Myeloma Group
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Percentage (Number) |
|---|
| Complete Remission | Partial Remission | Very Good Partial Response | Stringent Compete Response |
|---|
| Nivolumab + Ipilimumab | 0 | 0 | 0 | 0 |
,| Nivolumab Monotherapy (Expansion) | 3.7 | 0 | 0 | 0 |
Best Overall Response - Multiple Myeloma Group
the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy. (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Percentage (Number) |
|---|
| Complete Remission | Partial Remission |
|---|
| Nivolumab + Lirilumab | 0 | 0 |
Best Overall Response
"the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.~Measured in Complete Response and Partial Response" (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Percentage of participants (Number) |
|---|
| Complete Response | Partial Response |
|---|
| Nivolumab + Ipilimumab | 13.8 | 34.5 |
,| Nivolumab + Lirilumab | 9.7 | 29.0 |
,| Nivolumab Monotherapy (Expansion) | 10.4 | 33.8 |
Progression Free Survival in the Nivolumab + Daratumumab Cohort
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Months (Median) |
|---|
| Cohort A-1 | 7.56 |
| Cohort A-2 | 16.95 |
| Cohort B-1 | 6.57 |
| Cohort B-2 | 6.64 |
Overall Survival
The percentage of participants remaining alive. Median values are computed using Kaplan-Meier method (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to3 years Nivo Liri: approximately up to 4 years 1 month
| Intervention | Months (Median) |
|---|
| Nivolumab Monotherapy (Expansion) | 52.57 |
| Nivolumab + Ipilimumab | 30.39 |
| Nivolumab + Lirilumab | 14.95 |
Objective Response Rate in the Nivolumab + Daratumumab Cohort
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Percentage (Number) |
|---|
| Cohort A-1 | 66.7 |
| Cohort A-2 | 100 |
| Cohort B-1 | 53.7 |
| Cohort B-2 | 40.9 |
Duration of Response in the Nivolumab + Daratumumab Cohort
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Months (Median) |
|---|
| Cohort A-1 | NA |
| Cohort A-2 | NA |
| Cohort B-1 | 7.20 |
| Cohort B-2 | NA |
Duration of Response - Multiple Myeloma Group
"the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.~Measured in Complete Response and Partial Response" (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Months (Median) |
|---|
| Nivolumab Monotherapy (Expansion) | NA |
Duration of Response
"the best response designation over the study as a whole, recorded between the date of first dose and the last efficacy assessment prior to subsequent therapy.~Measured in Complete Remission and Partial Remission" (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to approximately 37 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Months (Median) |
|---|
| Nivolumab Monotherapy (Expansion) | 22.83 |
| Nivolumab + Ipilimumab | 24.84 |
| Nivolumab + Lirilumab | 19.38 |
Progression Free Survival
Progression free survival (PFS) is defined as the time between date of randomization and date of progression or death, whichever occurs first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Subjects who did not progress or die were censored on the date of their last efficacy assessment. (NCT01592370)
Timeframe: From date of randomization to date of progression or death, whichever occurs first (up to approximately 24 months)
| Intervention | Months (Median) |
|---|
| Nivolumab Monotherapy (Expansion) | 6.24 |
| Nivolumab + Ipilimumab | 6.93 |
| Nivolumab + Lirilumab | 3.02 |
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Hematology
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Hemoglobin72572291 | Hemoglobin72572292 | Hemoglobin72572293 | Hemoglobin72572294 | Platelet count72572292 | Platelet count72572291 | Platelet count72572293 | Platelet count72572294 | Leukocytes72572293 | Leukocytes72572291 | Leukocytes72572292 | Leukocytes72572294 | Lymphocytes (Absolute)72572291 | Lymphocytes (Absolute)72572292 | Lymphocytes (Absolute)72572293 | Lymphocytes (Absolute)72572294 | Absolute Neutrophil Count72572293 | Absolute Neutrophil Count72572291 | Absolute Neutrophil Count72572292 | Absolute Neutrophil Count72572294 |
|---|
| Grade 0 | Grade 2 | Grade 3 | Grade 4 | Grade 1 |
|---|
| Nivolumab + Daratumumab_Cohort B1 | 3 |
| Nivolumab + Daratumumab_Cohort B1 | 13 |
| Nivolumab + Daratumumab_Cohort B2 | 13 |
| Nivolumab + Daratumumab_Cohort B1 | 20 |
| Nivolumab + Daratumumab_Cohort B1 | 5 |
| Nivolumab + Daratumumab_Cohort B1 | 0 |
| Nivolumab + Daratumumab_Cohort A1 | 3 |
| Nivolumab + Daratumumab_Cohort A2 | 1 |
| Nivolumab + Daratumumab_Cohort B1 | 19 |
| Nivolumab + Daratumumab_Cohort B2 | 8 |
| Nivolumab + Daratumumab_Cohort A1 | 2 |
| Nivolumab + Daratumumab_Cohort A2 | 3 |
| Nivolumab + Daratumumab_Cohort B1 | 11 |
| Nivolumab + Daratumumab_Cohort B2 | 9 |
| Nivolumab + Daratumumab_Cohort B2 | 3 |
| Nivolumab + Daratumumab_Cohort A1 | 0 |
| Nivolumab + Daratumumab_Cohort B2 | 0 |
| Nivolumab + Daratumumab_Cohort A1 | 1 |
| Nivolumab + Daratumumab_Cohort A2 | 0 |
| Nivolumab + Daratumumab_Cohort B2 | 1 |
| Nivolumab + Daratumumab_Cohort B1 | 10 |
| Nivolumab + Daratumumab_Cohort B1 | 15 |
| Nivolumab + Daratumumab_Cohort B1 | 9 |
| Nivolumab + Daratumumab_Cohort B2 | 2 |
| Nivolumab + Daratumumab_Cohort B1 | 1 |
| Nivolumab + Daratumumab_Cohort B2 | 7 |
| Nivolumab + Daratumumab_Cohort B2 | 5 |
| Nivolumab + Daratumumab_Cohort A2 | 2 |
| Nivolumab + Daratumumab_Cohort B1 | 2 |
| Nivolumab + Daratumumab_Cohort B1 | 14 |
| Nivolumab + Daratumumab_Cohort B2 | 10 |
| Nivolumab + Daratumumab_Cohort B1 | 8 |
| Nivolumab + Daratumumab_Cohort B1 | 6 |
| Nivolumab + Daratumumab_Cohort B2 | 6 |
| Nivolumab + Daratumumab_Cohort B1 | 4 |
Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
Time to MRD Negativity status in specific NGS and NGF sensitivity levels (NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Months (Mean) |
|---|
| NGS sensitivity level=10e-4 | NGS sensitivity level=10e-5 | NGF sensitivity level=10e-4 | NGF sensitivity level=10e-5 | NGF sensitivity level=10e-6 |
|---|
| Cohort B-1 | 3.60 | 5.45 | 2.94 | 6.97 | 12.30 |
Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
Time to MRD Negativity status in specific NGS and NGF sensitivity levels (NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Months (Mean) |
|---|
| NGS sensitivity level=10e-4 | NGS sensitivity level=10e-5 | NGS sensitivity level=10e-6 |
|---|
| Cohort A-1 | 3.02 | 3.02 | 30.85 |
Time to MRD Negativity Status in the Nivolumab + Daratumumab Cohort
Time to MRD Negativity status in specific NGS and NGF sensitivity levels (NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Months (Mean) |
|---|
| NGS sensitivity level=10e-4 | NGF sensitivity level=10e-4 |
|---|
| Cohort B-2 | 2.83 | 4.20 |
Progression Free Survival Rate
The percentage of participants remaining progression free at the specified timepoints (up to 48 Months) (NCT01592370)
Timeframe: From randomization to the specified timepoints (up to 48 months)
| Intervention | Percentage of Participants (Number) |
|---|
| 6 Months | 12 Months | 18 Months | 24 Months | 36 Months | 48 Months |
|---|
| Nivolumab Monotherapy (Expansion) | 50.5 | 34.8 | 31.0 | 20.3 | 15.8 | 13.2 |
Progression Free Survival Rate
The percentage of participants remaining progression free at the specified timepoints (up to 48 Months) (NCT01592370)
Timeframe: From randomization to the specified timepoints (up to 48 months)
| Intervention | Percentage of Participants (Number) |
|---|
| 6 Months | 12 Months | 18 Months | 24 Months |
|---|
| Nivolumab + Ipilimumab | 51.5 | 45.3 | 40.1 | 30.9 |
Progression Free Survival Rate
The percentage of participants remaining progression free at the specified timepoints (up to 48 Months) (NCT01592370)
Timeframe: From randomization to the specified timepoints (up to 48 months)
| Intervention | Percentage of Participants (Number) |
|---|
| 2 Months | 4 Months | 6 Months | 9 Months |
|---|
| Nivolumab + Lirilumab | 58.0 | 42.4 | 34.3 | 32.5 |
Number of Participants With PD-L1 Expression
"Number of Participants with PD-L1 expression in the following categories~baseline PD-L1 expression ≥ 1%~baseline PD-L1 expression < 1%~without PD-L1 quantifiable at baseline" (NCT01592370)
Timeframe: At baseline (prior to start of study treatment)
| Intervention | Number of Participants (Number) |
|---|
| Baseline PD-L1 expression ≥ 1% | Baseline PD-L1 expression < 1% | PD-L1 not quantifiable at baseline |
|---|
| Nivolumab + Ipilimumab | 26 | 14 | 25 |
,| Nivolumab + Lirilumab | 16 | 20 | 36 |
,| Nivolumab Monotherapy (Expansion) | 25 | 16 | 64 |
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Thyroid
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| TSH>ULN | TSH > ULN WITH TSH <= ULN AT BASELINE | TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN (A) | TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | WITH FT3/FT4 TEST MISSING | TSH < LLN | TSH < LLN WITH TSH >= LLN AT BASELINE | TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN | TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | TSH < LLN WITH FT3/FT4 TEST MISSING |
|---|
| Nivolumab + Daratumumab_Cohort A1 | 3 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
,| Nivolumab + Daratumumab_Cohort A2 | 1 | 1 | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 2 |
,| Nivolumab + Daratumumab_Cohort B1 | 8 | 7 | 1 | 5 | 2 | 2 | 2 | 0 | 1 | 1 |
,| Nivolumab + Daratumumab_Cohort B2 | 3 | 2 | 0 | 2 | 1 | 2 | 1 | 0 | 2 | 0 |
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade in the Nivolumab + Daratumumab Cohort - Liver
(NCT01592370)
Timeframe: approximately up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| ALT or AST >3xULN | ALT or AST >5xULN | ALT or AST >10xULN | ALT or AST >20xULN | Total Bilirubin > 2xULN | ALT or AST >3xULN with total Bilirubin > 2xULN within 1 day | ALT or AST >3xULN with total Bilirubin >2xULN within 30 days |
|---|
| Nivolumab + Daratumumab_Cohort A1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 |
,| Nivolumab + Daratumumab_Cohort A2 | 0 | 3 | 3 | 3 | 3 | 3 | 3 |
,| Nivolumab + Daratumumab_Cohort B1 | 0 | 9 | 9 | 9 | 9 | 9 | 9 |
,| Nivolumab + Daratumumab_Cohort B2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Thyroid
(NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Participants (Count of Participants) |
|---|
| TSH > ULN | TSH > ULN WITH TSH <= ULN AT BASELINE | TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN | TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | TSH > ULN WITH FT3/FT4 TEST MISSING | TSH < LLN | TSH < LLN WITH TSH >= LLN AT BASELINE | TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN | TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | TSH < LLN WITH FT3/FT4 TEST MISSING |
|---|
| Nivolumab + Ipilimumab | 19 | 13 | 7 | 1 | 11 | 6 | 6 | 1 | 0 | 5 |
,| Nivolumab + Lirilumab | 15 | 9 | 1 | 1 | 13 | 6 | 4 | 1 | 0 | 5 |
,| Nivolumab Monotherapy (Expansion) | 14 | 11 | 0 | 1 | 13 | 8 | 5 | 0 | 0 | 8 |
Number of Participants With Clinical Laboratory Abnormalities by Worst Toxicity Grade - Liver
Number and percent of participants that experienced drug related Grade 3-4 AEs occurring up to 100 days after the last dose of study drug. (NCT01592370)
Timeframe: Nivo Mono: approximately up to 6 years and 9 months Nivo Ipi: approximately up to 5 months Nivo Liri: approximately up to 4 years 1 month
| Intervention | Participants (Count of Participants) |
|---|
| ALT OR AST > 3XULN | ALT OR AST > 5XULN | ALT OR AST > 10XULN | ALT OR AST > 20XULN | TOTAL BILIRUBIN > 2XULN | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS |
|---|
| Nivolumab + Ipilimumab | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
,| Nivolumab + Lirilumab | 4 | 2 | 1 | 0 | 2 | 1 | 1 |
,| Nivolumab Monotherapy (Expansion) | 3 | 1 | 1 | 1 | 1 | 1 | 1 |
End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort
Serum concentration achieved at the end of study drug infusion (NCT01592370)
Timeframe: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
| Intervention | ug/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 | Cycle 3 | Cycle 5 | Cycle 7 | Cycle 11 |
|---|
| Cohort B-1 | 69.59 | 175.73 | 193.38 | 208.14 | 193.00 | 212.00 |
End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort
Serum concentration achieved at the end of study drug infusion (NCT01592370)
Timeframe: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
| Intervention | ug/mL (Mean) |
|---|
| Cycle 1 | Cycle 3 | Cycle 7 |
|---|
| Cohort A-1 | 57.28 | 105.14 | 227.75 |
End of Infusion Nivolumab Concentration Levels in the Nivolumab + Daratumumab Cohort
Serum concentration achieved at the end of study drug infusion (NCT01592370)
Timeframe: Measurements collected at cycles 1, 2, 3, 5, 7, and 11; each cycle is 28 days
| Intervention | ug/mL (Mean) |
|---|
| Cycle 7 | Cycle 11 |
|---|
| Cohort A-2 | 206.00 | 206.00 |
Toxicity
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. (NCT01688466)
Timeframe: 50 months and 20 days
| Intervention | Participants (Count of Participants) |
|---|
| 0.5 mg/Day With Dose Escalation | 17 |
| 0.5 mg/Day Without Dose Escalation | 17 |
Overall Response at 6 Months
Overall response was assessed by the National Institutes of Health (NIH) Chronic Graft-Versus Host Disease (cGVHD) Response criteria. Complete response (CR) is complete resolution in all signs and symptoms at all affected organs or tissues. Partial response (PR) is improvement in ≥ 1 organ or tissue with no progression in any other affected organ or tissue. Response < PR is a change towards improvement from the pre-treatment baseline but not meeting the criteria for CR or PR. Stable disease (SD) is no change in cGVHD. Flare is exacerbation of cGVHD manifestations during withdrawal of immunosuppressive therapy which do not exceed those at the beginning of the trial and improves after reinstatement of previous treatment. Progressive disease (PD) is failure of therapy to control cGVHD . Mixed response (improvement in some organs but worsening in others) will be categorized as progressive disease. (NCT01688466)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Progressive Disease | Stable Disease | Mixed Response | Response < Partial Response | Flare | Did not respond to treatment | Not Evaluable |
|---|
| 0.5 mg/Day With Dose Escalation | 0 | 7 | 2 | 0 | 0 | 0 | 0 | 1 | 7 |
,| 0.5 mg/Day Without Dose Escalation | 0 | 9 | 5 | 1 | 0 | 0 | 0 | 0 | 2 |
Pomalidomide Exposure - Apparent Volume of Distribution (V/F)
Pharmacokinetic (PK) parameters are derived from Pomalidomide concentration versus time data. (NCT01712789)
Timeframe: Cycles 1, 2, 3, 4, 5, 6
| Intervention | Liters (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 75.10 |
Pomalidomide Exposure - Apparent (Oral) Clearance (CL/F)
Pharmacokinetic (PK) parameters are derived from pomalidomide concentration versus time data. (NCT01712789)
Timeframe: Cycles 1, 2, 3, 4, 5, 6
| Intervention | Liters/hour (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 6.02 |
Overall Response
Overall response rate (ORR) was defined as the percentage of participants with a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) according to the International Myeloma Working Group uniform response criteria (IMWG URC) assessed by the Investigator. Responses must have been confirmed at at least 2 consecutive assessments before the institution of any new therapy with no known evidence of progressive or new bone lesions (NCT01712789)
Timeframe: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 33.4 |
Kaplan Meier Estimate of Time to Progression
Time to progression was calculated as the time from study enrollment until first recorded disease progression as determined by the site investigator based on the IMWG criteria, or until death due to progression. Participants not experiencing a documented progression were censored at the time of their last tumor assessment (or at the time of trial enrollment if no assessment was conducted). (NCT01712789)
Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
| Intervention | Months (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 4.8 |
Kaplan Meier Estimate of Progression Free Survival (PFS) According to the European Medicines Agency Guidelines
Progression free survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until either PD or death (any cause). Participants without an event (either a documented PD or death) at the time of study end were censored at the time of their last documented disease assessment or at the IVRS enrollment date if no disease assessment was conducted. (NCT01712789)
Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
| Intervention | Months (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 4.6 |
Kaplan Meier Estimate of Overall Survival (OS)
Overall survival was calculated as the time from study enrollment, defined as the IVRS enrollment date, until death due to any cause. Participants who did not have death data at the time of study end/analysis were censored at the time they were last known to be alive. (NCT01712789)
Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
| Intervention | Months (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 11.9 |
Time to Response
Time to response was defined as the time from treatment enrollment to the first documentation of response (sCR, CR, VGPR or PR) based on IMWG criteria. (NCT01712789)
Timeframe: Response was assessed at each treatment cycle and at treatment discontinuation; median duration of treatment with pomalidomide and LD-dex was 21.4 weeks
| Intervention | Weeks (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 8.1 |
Number of Participants With Treatment Emergent Adverse Events (TEAE)
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject 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 subject's health, regardless of etiology. Any worsening (i.e., any significant adverse change in the frequency or intensity of a pre- existing condition) was considered an AE. The severity of AEs were graded based on the symptoms according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs.~A SAE = AE occurring at any dose that:~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" (NCT01712789)
Timeframe: From the first dose of study treatment up to 28 days following the last dose of study treatment. The median duration of treatment with pomalidomide and LD-dex was 21.4 weeks.
| Intervention | Participants (Count of Participants) |
|---|
| ≥ TEAE | ≥ 1 TEAE Related to Pomalidomide (POM) | ≥ 1 TEAE Related to LD-Dex | ≥ 1 TEAE Related to Either POM or LD-Dex | ≥ 1 Grade (Gr) 3 or 4 TEAE | ≥ 1 Gr 3 or 4 TEAE Related to (R/T) POM | ≥ 1 Gr 3 or 4 TEAE R/T LD-Dex | ≥ 1 Gr 3 or 4 TEAE R/T Either POM or LD-Dex | ≥ 1 Grade 5 TEAE | ≥ 1 Grade 5 TEAE R/T POM | ≥ 1 Grade 5 TEAE R/T LD-Dex | ≥ 1 Grade 5 TEAE R/T either POM or LD-Dex | ≥ 1 Serious TEAE | ≥ 1 Serious TEAE R/T POM | ≥ 1 Serious TEAE R/T LD-Dex | ≥ 1 Serious TEAE R/T Either POM or LD-Dex | ≥ 1 Serious TEAE Leading to (L/T)Stopping of POM | ≥ 1 Serious TEAE L/T Stopping of LD-Dex | ≥1 Serious TEAE L/T Stopping either POM or LD-Dex | ≥ 1 TEAE L/T to Stopping of POM | ≥ 1 TEAE L/T to Stopping of LD-DEX | ≥ 1 TEAE L/T to Stopping of Either POM or LD-DEX | ≥1 Study Drug Related TEAE (L/T) Stopping POM | ≥1 Study Drug Related TEAE L/T Stopping LD-Dex | ≥1 Drug Related TEAE L/T Stopping LD-Dex or POM | ≥ 1 TEAE L/T to Reduction (R/D) of POM | ≥ 1 TEAE L/T to R/D of LD-DEX | ≥ 1 TEAE L/T to R/D of Either POM or LD-DEX | ≥ 1 Study Drug Related TEAE L/T to R/D of POM | ≥ 1 Study Drug Related TEAE L/T to R/D of LD-DEX | ≥1 StudyDrug Related TEAE L/T to R/D POM or LD-DEX | ≥ 1 TEAE L/T to Interruption (I/R) of POM | ≥ 1 TEAE L/T to I/R of LD-DEX | ≥ 1 TEAE L/T to I/R of either POM or LD-DEX | ≥ 1 Study Drug Related TEAE L/T to I/R of POM | ≥ 1 Study Drug Related TEAE L/T to I/R of LD-DEX | ≥1 StudyDrug Related TEAE L/T to I/R POM or LD-DEX |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 673 | 527 | 448 | 575 | 606 | 417 | 226 | 448 | 127 | 14 | 16 | 18 | 448 | 187 | 146 | 215 | 36 | 34 | 37 | 54 | 61 | 63 | 30 | 19 | 38 | 164 | 150 | 244 | 142 | 135 | 224 | 455 | 434 | 470 | 294 | 185 | 333 |
Kaplan Meier Estimate of Duration of Response
Duration of response, calculated for responders only, was defined as time from the initial documented response (SCR, CR, VGPR or PR) to the first confirmed disease progression, or death if no disease progression was recorded. Participants without a documented progression were censored at the time of their last tumor assessment. (NCT01712789)
Timeframe: From enrollment to the end of follow-up; median time on follow-up was 10.9 (range 0 - 81) months
| Intervention | Months (Median) |
|---|
| Pomalidomide Plus Low Dose Dexamethasone (LD-Dex) | 7.9 |
Duration of Response by Independent Response Adjudication Committee (IRAC)
"Duration of myeloma response is defined as the duration from the time when the IMWG response criteria are first met for sCR or CR or VGPR or PR until the first date the response criteria are met for PD or until the subject died from any cause, whichever occurs first.~Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow~SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence~VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level < 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~Progressive Disease: Please refer to Primary outcome measure for definition~SD: Not meeting criteria for CR, VGPR, PR, or progressive disease" (NCT01734928)
Timeframe: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
| Intervention | Months (Median) |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 13.70 |
| Treatment 2: BTZ+LD-DEX | 10.94 |
Number of Participants With Grade 3-4 Treatment Emergent Adverse Events (TEAE)
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first dose date of the study treatment and within 28 days after the last dose date. (NCT01734928)
Timeframe: From first dose to 28 days after the last dose (up to approximately 44 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 259 |
| Treatment 2: BTZ+LD-DEX | 194 |
Number of Participants With Grade 5 Treatment Emergent Adverse Events (TEAE)
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first dose date of the study treatment and within 28 days after the last dose date. (NCT01734928)
Timeframe: From first dose to 28 days after the last dose (up to approximately 44 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 29 |
| Treatment 2: BTZ+LD-DEX | 12 |
Overall Survival (OS)
Overall survival (OS) is calculated as the time from randomization to death from any cause. (NCT01734928)
Timeframe: From randomization to date of death, up to approximately 65 months
| Intervention | Months (Median) |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 35.58 |
| Treatment 2: BTZ+LD-DEX | 31.61 |
Progression Free Survival by Independent Response Adjudication Committee (IRAC)
"Progression free survival (PFS) will be calculated as the time between the randomization and progressive disease (PD) or death.~Progressive Disease is defined as an Increase of ≥ 25% from nadir in:~Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)g~Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 hours)~In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels, the absolute increase must be > 100 mg/dL.~Bone marrow plasma cell percentage, the absolute % must be ≥ 10%h~Definite development of new bone lesions or soft tissue plasmacytomas 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." (NCT01734928)
Timeframe: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
| Intervention | Months (Median) |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 11.20 |
| Treatment 2: BTZ+LD-DEX | 7.10 |
Overall Response Rate by Independent Response Adjudication Committee (IRAC)
"The ORR together with the relative proportions in each response category (ie, stringent CR [sCR], CR, very good PR [VGPR], PR, SD, and PD) by treatment using the IMWG criteria will be examined.~Complete Response: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow~SCR: CR+ Normal FLC ratio and Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence~VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level < 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~Progressive Disease: Please refer to Primary outcome measure for definition~SD: Not meeting criteria for CR, VGPR, PR, or progressive disease" (NCT01734928)
Timeframe: From randomization to progressive disease or death during the IRAC assessment period, up to approximately 42 months
| Intervention | Participants (Count of Participants) |
|---|
| Stringent complete response | Complete Reponse | Very Good Partial Response | Partial Response | Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Treatment 1: POM+BTZ+LD-DEX | 9 | 35 | 104 | 83 | 32 | 11 | 7 |
,| Treatment 2: BTZ+LD-DEX | 2 | 9 | 40 | 88 | 106 | 16 | 17 |
Initial Response Rate
"The number of patients achieving a complete response (CR) or partial response (PR). Response is defined by the International Myeloma Working Group as:~CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and < 5% plasma cells in bone marrow~PR- > 50% reduction of serum M-protein and urine M-protein by >90% or to < 200 mg/24 h In addition, if present at baseline, a > 50% reduction in the size of soft tissue plasmacytomas is also required~VGPR - Serum and urine M-protein detectable by immunofixation but n" (NCT01754402)
Timeframe: 2 cycles (approximately 2 months)
| Intervention | Participants (Count of Participants) |
|---|
| Partial Response | Very Good Partial Response | Complete Response |
|---|
| Cohort 1: 120mg Bendamustine + 3mg Pomalidomide | 1 | 0 | 0 |
,| Expansion: 120mg Bendamustine + 3mg Pomalidomide | 11 | 2 | 0 |
Maximum Tolerated Dose of Pomalidomide and Bendamustine
"In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) is reached.~Cohort 1 (bendamustine 120mg/m2 + pomalidomide 3mg); Cohort 2 (bendamustine 120mg/m2 + pomalidomide 4mg); Cohort 3 (bendamustine 150mg/m2 + pomalidomide 4mg); Cohort 4 (bendamustine 180mg/m2 + pomalidomide 4mg)~If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD)." (NCT01754402)
Timeframe: 2 cycles (approximately 2 months)
| Intervention | milligrams (Number) |
|---|
| Pomalidomide | Bendamustine |
|---|
| Cohorts 1 and 2 | 3 | 120 |
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 |
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 |
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 |
Number of Participants With Progression-free Survival
(NCT01946152)
Timeframe: Up to 6 years
| Intervention | Participants (Count of Participants) |
|---|
| Maximum Tolerated Dosage (MTD) | 3 |
Number of Participants Recommended Phase II Dose of Pomalidomide and Dexamethasone, When Both Agents Are Administered Together With Granulocyte-colony Stimulating Factor (Filgrastim) (Phase I)
(NCT01946152)
Timeframe: Up to 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Maximum Tolerated Dose (MTD) | 8 |
Maximum Tolerated Dose (MTD) (Phase I)
Safety and tolerability will be assessed by clinical review of all relevant parameters, including dose limiting toxicities. Toxicity type and severity will be summarized by frequency tables. Maximum tolerated dose defined as the highest dose level in which patients have been treated with less than 2 instances of dose-limiting toxicity (Phase I) (NCT01946152)
Timeframe: 28 days
| Intervention | mg (Number) |
|---|
| Maximum Tolerated Dose (MTD) | 5 |
Time to Disease Progression (Progression Free Survival)
(NCT01979276)
Timeframe: From start of treatment, to date of disease progression (on average, ten 28-day cycles)
| Intervention | cycles (defined as 28 days) (Mean) |
|---|
| ALL Patients | 9.5 |
Number of Participants With Post-Baseline Grade 3 or 4 Laboratory Toxicities
"Laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03).~Full chemistry panel included sodium, potassium, calcium, alkaline phosphatase, blood urea nitrogen, uric acid, lactate dehydrogenase, creatinine, chloride, bicarbonate, glucose, total protein, albumin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), phosphorous, and magnesium.~Complete blood count (CBC) with differential included hemoglobin, hematocrit, white blood cell (WBC) count with complete manual or automated differential (total neutrophils, lymphocytes, monocytes, eosinophils, basophils; reported as absolute counts), red blood cell (RBC) count, and platelet count." (NCT01999335)
Timeframe: Cycles 1 and 2 days 1, 5, 15, and 19 and days 3 and 8 of cycle 1, and day 1 of each cycle from cycle 3 thereafter until the end of treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| At least 1 Grade 3 or 4 laboratory toxicity | Grade 3 increase in glucose | Grade 4 increase in glucose | Grade 3 increase in total bilirubin | Grade 3 increase in magnesium | Grade 4 decrease in magnesium | Grade 3 decrease in sodium | Grade 4 decrease in sodium | Grade 3 decrease in hemoglobin | Grade 3 decrease in leukocytes | Grade 4 decrease in leukocytes | Grade 3 decrease in neutrophils | Grade 4 decrease in neutrophils | Grade 3 decrease in lymphocytes | Grade 4 decrease in lymphocytes | Grade 3 decrease in platelets |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
,| Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 1 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 3 | 0 | 5 | 0 | 0 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase | 8 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 2 | 1 | 4 | 2 | 4 | 0 | 5 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 8 | 1 | 1 | 1 | 0 | 1 | 3 | 1 | 1 | 1 | 0 | 1 | 0 | 3 | 2 | 2 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
"Adverse events (AEs) were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (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 (TRAE) are those considered related to at least 1 study drug by the investigator." (NCT01999335)
Timeframe: From first dose of any study drug up to 30 days after the last dose; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Any treatment-emergent adverse event | TEAE Grade ≥ 3 | Serious adverse events | TEAEs leading to discontinuation of study drug | Fatal adverse events | Treatment-related treatment-emergent adverse events (TRAE) | Treatment-related TEAE Grade ≥ 3 | Treatment-related serious adverse events | TRAEs leading to discontinuation of study drug | Treatment-related fatal adverse events |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone | 3 | 2 | 0 | 1 | 0 | 3 | 2 | 0 | 1 | 0 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 7 | 5 | 3 | 2 | 0 | 7 | 4 | 1 | 1 | 0 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase | 10 | 9 | 6 | 4 | 0 | 10 | 7 | 2 | 4 | 0 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 10 | 9 | 6 | 1 | 0 | 10 | 6 | 2 | 1 | 0 |
Time to Maximum Plasma Concentration (Tmax) of Oprozomib
Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. (NCT01999335)
Timeframe: Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
| Intervention | hours (Median) |
|---|
| Cycle 1 day 1 | Cycle 2 day 1 |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone | 1.0 | 4.0 |
,| Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone | 1.6 | 1.1 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 2.2 | 1.1 |
Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib
"Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.~The area under the plasma concentration-time curve from time 0 to time infinity (AUCinf), estimated as the sum of AUClast and Clast/λz, where Clast is the last predicted concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase." (NCT01999335)
Timeframe: Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Cycle 1 day 1 |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone | 2250 |
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of Oprozomib
"Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.~The area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method." (NCT01999335)
Timeframe: Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Cycle 1 day 1 | Cycle 2 day 1 |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone | 1090 | 446 |
,| Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone | 1700 | 1860 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 1730 | 1800 |
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 the difference between involved and uninvolved free light chain levels (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 serum FLC (SFLC), ≥ 90% decrease in dFLC.~CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow (BM). Normal SFLC ratio if disease measurable only by SFLC.~sCR: As for CR, and absence of clonal plasma cells in BM." (NCT01999335)
Timeframe: Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
| Intervention | percentage of participants (Number) |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone | 33.3 |
| Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone | 100.0 |
| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 85.7 |
| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 60.0 |
| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase | 60.0 |
Maximum Plasma Concentration (Cmax) of Oprozomib
Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. (NCT01999335)
Timeframe: Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1 day 1 | Cycle 2 day 1 |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide + Dexamethasone | 492 | 181 |
,| Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone | 744 | 1030 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 757 | 965 |
Number of Participants With Dose-limiting Toxicities (DLTs)
"DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03, defined as any of the following treatment-related events occurring within 4 weeks after the first dose of therapy:~Any grade ≥ 3 nonhematologic toxicity, except: Grade 3 asymptomatic electrolyte abnormalities or hypophosphatemia for < 24 hours; Grade 3 nausea, vomiting or diarrhea unless for > 3 days despite optimal supportive care; Grade 3 fatigue for < 14 days; Grade ≥ 3 hyperglycemia or toxicity attributed to dexamethasone and Grade ≥ 3 rash attributed to pomalidomide.~Hematologic toxicities:~Grade 4 neutropenia: Absolute neutrophil count < 0.5 × 10^9/L for ≥ 7 days despite adequate growth factor support; febrile neutropenia~Thrombocytopenia: Grade 4 for ≥ 7 days, or Grade 4 for < 7 days with grade 2 clinically significant bleeding or < 10,000 platelets requiring transfusion, or Grade 3 with clinically significant bleeding or requiring platelet transfusion." (NCT01999335)
Timeframe: Cycle 1, 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Any dose-limiting toxicity | Gastric hemorrhage | Abdominal distension | Cognitive disorder | Mucosal inflammation |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone | 0 | 0 | 0 | 0 | 0 |
,| Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone | 2 | 0 | 1 | 1 | 1 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 1 | 1 | 0 | 0 | 0 |
,| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase | 0 | 0 | 0 | 0 | 0 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 0 | 0 | 0 | 0 | 0 |
Clinical Benefit Rate (CBR)
"Clinical benefit rate is defined as the percentage of participants with a best overall response of minimal response (MR) per modified European Group for Blood and Marrow Transplantation criteria, or PR, VGPR, CR, or sCR as determined by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC).~MR:~≥ 25% but < 49% reduction in serum M-protein and a 50 - 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg per 24 hours~If the serum and urine M-protein were not measurable, a decrease of 25 - 49% in the difference between involved and uninvolved FLC levels was required in place of the M-protein criteria.~For patients with nonsecretory myeloma only, 25 - 49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed~25 - 49% reduction in the size of soft tissue plasmacytomas (by radiography or clinical examination)" (NCT01999335)
Timeframe: Disease response was assessed every 4 weeks for the first 18 months and then every 8 weeks for the remainder of study treatment; median duration of treatment was 7.6, 28.0, 32.1, 46.3, and 17.4 weeks in each treatment group, respectively.
| Intervention | percentage of participants (Number) |
|---|
| Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone | 33.3 |
| Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone | 100.0 |
| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 85.7 |
| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 60.0 |
| Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase | 60.0 |
Area Under the Plasma Concentration-time Curve From Time 0 to Time Infinity (AUCinf) of Oprozomib
"Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.~The area under the plasma concentration-time curve from time 0 to time infinity (AUCinf), estimated as the sum of AUClast and Clast/λz, where Clast is the last predicted concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase." (NCT01999335)
Timeframe: Cycle 1 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours postdose. Cycle 2 day 1 at predose and 0.25, 0.5, 1, 2, 3, 4, and 6 hours postdose.
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Cycle 1 day 1 | Cycle 2 day 1 |
|---|
| Oprozomib 210 mg 2/7 + Pomalidomide + Dexamethasone | 3440 | 1830 |
,| Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone | 1660 | 1900 |
Overall Response Rate (ORR)
ORR is defined as partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) according to International Myeloma Working Group (IMWG) Uniform Response Criteria (NCT02004275)
Timeframe: 3 years
| Intervention | proportion of participants (Number) |
|---|
| Arm I (Pomalidomide, Dexamethasone) | .436 |
| Arm II (Pomalidomide, Dexamethasone, Ixazomib) | .632 |
Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)
For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event (NCT02004275)
Timeframe: 28 days
| Intervention | participants with DLT (Number) |
|---|
| Phase 1 Dose Level 1 | 0 |
| Phase 1 Dose Level 2 | 0 |
| Phase 1 Dose Level 3 | 1 |
| Phase 1 Dose Level 4 | 1 |
Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)
(NCT02004275)
Timeframe: Up to 3 years post-registration (at crossover)
| Intervention | months (Median) |
|---|
| Arm I (Pomalidomide, Dexamethasone) | 5.6 |
Progression Free Survival (PFS) (Phase II)
progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no (NCT02004275)
Timeframe: 3 years
| Intervention | days (Median) |
|---|
| Phase II Arm I (Pomalidomide, Dexamethasone) | 228 |
| Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) | 619 |
Overall Survival (OS) (Phase II)
Overall survival was analyzed from the time of registration to the date of death or last known date living. Due to median OS time not being reached due to lack of deaths at the time of this report by either arm, the 2 year OS rate has been reported. This analysis censors living patients at 2 years. (NCT02004275)
Timeframe: 2 years
| Intervention | proportion of patients alive (Number) |
|---|
| Phase II Arm I (Pomalidomide, Dexamethasone) | .795 |
| Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) | .784 |
Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II)
(NCT02004275)
Timeframe: Up to 3 years
| Intervention | proportion of partcipants (Number) |
|---|
| Overall Response Rate | Clinical Benefit Rate | Disease Control Rate |
|---|
| Arm I(Pomalidomide, Dexamethasone) | .231 | .269 | .962 |
Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II)
(NCT02004275)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Phase II Arm I (Pomalidomide, Dexamethasone) | 12.3 |
| Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) | 23.7 |
Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I)
These events are reported in the adverse events section of this report. (NCT02004275)
Timeframe: 44.5 months
| Intervention | participants with DLT (Number) |
|---|
| Phase 1 Dose Level 1 | 0 |
| Phase 1 Dose Level 2 | 0 |
| Phase 1 Dose Level 3 | 1 |
| Phase 1 Dose Level 4 | 1 |
Incidence of Dose Reductions/Delays (Phase I)
(NCT02004275)
Timeframe: 39 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Level 1 | 2 |
| Phase 1 Dose Level 2 | 3 |
| Phase 1 Dose Level 3 | 6 |
| Phase 1 Dose Level 4 | 5 |
Clinical Benefit Rate (CBR)
Disease response status is based on the IMWG criteria being held for two consecutive evaluations at least 4 weeks apart. Clinical benefit rate (CBR) is defined as proportion of patients with minimal response (MR) and better according to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II) (NCT02004275)
Timeframe: 3 years
| Intervention | proportion of participants (Number) |
|---|
| Phase II Arm I (Pomalidomide, Dexamethasone) | .564 |
| Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) | .737 |
Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II)
The count of paitents that experenced an adverse event is reported in this section. A full table of these events is reported in the adverse event section of this report. (NCT02004275)
Timeframe: 92 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Arm I (Pomalidomide, Dexamethasone) | 22 |
| Phase II Arm II (Pomalidomide, Dexamethasone, Ixazomib) + Crossover Patients From Arm I | 33 |
| Phase 1 Dose Level 1 | 2 |
| Phase 1 Dose Level 2 | 2 |
| Phase 1 Dose Level 3 | 4 |
| Phase 1 Dose Level 4 | 6 |
Number of Participants With Adverse Events
Relation to study drug was assessed by the Investigator as either suspected or not suspected. Counts represent the suspected relationship. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0): 1= Mild 2= Moderate 3= Severe 4= Life-threatening and 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. Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring on or after the first treatment of the study medication and within 28 days after the last dose. (NCT02011113)
Timeframe: From first dose of study drug to final data cut-off date of 25 Sept 2015, maximum duration on treatment was 80.9 weeks
| Intervention | participants (Number) |
|---|
| Any 1 TEAE | TEAE related to any study drugs | TEAE related to Pomalidomide | TEAE related to Dexamethasone(Dex) | TEAE with ≥ Grade (GR) 3 | ≥ 1TEAE ≥ GR 3 related to any study drug | TEAE ≥ GR 3 related to Pomalidomide | TEAE ≥ GR 3 related to Dexamethasone | ≥ 1 serious TEAE | Serious TEAE related to any study drug | Serious TEAE related to Pomalidomide | Serious TEAE related to Dexamethasone | TEAE leading to stopping of any study drug | TEAE leading to discontinuation of Pomalidomide | TEAE leading to discontinuation of Dexamethasone | Related TEAE leading to stopping of study drug | Related TEAE leading to stopping of Pomalidomide | Related TEAE leading to stopping Dexamethasone | TEAE leading to dose reduction of any study drug | TEAE leading to dose reduction of Pomalidomide | TEAE leading to dose reduction of Dexamethasone | TEA leading to dose interruption of any study drug | TEAE leading to dose interruption of Pomalidomide | TEAE leading to dose interruption of Dexamethasone | Related TEAE leading to dose reduction of any drug | Related TEAE causing a dose reduction Pomalidomide | ≥1 related TEAE causing a dose reduction: Dex | Related TEAE leading to interruption of drugs | Related TEAE causing an interruption Pomalidomide | Related TEAE causing an interruption to Dex | TEAE Grade 5 |
|---|
| Pomalidomide Plus Dexamethasone | 36 | 33 | 33 | 27 | 33 | 30 | 30 | 11 | 16 | 8 | 8 | 6 | 5 | 5 | 5 | 4 | 4 | 4 | 19 | 10 | 15 | 20 | 18 | 11 | 18 | 10 | 14 | 16 | 15 | 8 | 3 |
Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria
Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions. (NCT02011113)
Timeframe: From first dose until the data cut-off date of 03 September 2014; maximum time in follow-up was 36.0 weeks
| Intervention | percentage of participants responding (Number) |
|---|
| Pomalidomide Plus Dexamethasone | 22.2 |
Kaplan-Meier Estimates of Duration of Response (Later Cut-off Date)
Duration of response (calculated for responders only) was defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria. (NCT02011113)
Timeframe: From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Dexamethasone | NA |
Kaplan-Meier Estimates of PFS (Later Cut-off Date)
PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier (NCT02011113)
Timeframe: From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Dexamethasone | 32.10 |
Kaplan-Meier Estimates of Progression-free Survival (PFS)
PFS was calculated as the time from the first dosing to the first documented progressive disease, as determined by the investigators based on the IMWG Uniform Response criteria, or death, whichever occurred earlier (NCT02011113)
Timeframe: From the first dose until the data cut-off date of 03 September 2014; maximum time on treatment was 36.0 weeks
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Dexamethasone | 19.0 |
Myeloma Response Rate Based on European Group for Blood and Marrow Transplantation (EBMT) Criteria (Later Cut-off Date)
Myeloma response was defined as a best overall response of complete response (CR) or partial response (PR) CR is defined as: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - <5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to < 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions. (NCT02011113)
Timeframe: From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks
| Intervention | percentage of participants responding (Number) |
|---|
| Pomalidomide Plus Dexamethasone | 38.9 |
Time to Response
Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG 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. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required. (NCT02011113)
Timeframe: From the first dose until the data cut-off date of 03 September 2014. Maximum time on follow-up was 36.0 weeks.
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Dexamethasone | 4.10 |
Time to Response (Later Cut-off Date)
Time to response was calculated as the time from the first dose to the initial documented response (partial response or better) based on IMWG 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. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required. (NCT02011113)
Timeframe: From the first dose until the final data cut-off date of 25 September 2015; maximum duration on treatment was 80.9 weeks
| Intervention | weeks (Median) |
|---|
| Pomalidomide Plus Dexamethasone | 8.10 |
One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D)
Progression-free survival (PFS) was defined as time from initial treatment to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.] (NCT02119468)
Timeframe: Date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, up to 24 months. And the median follow-up for the surviving patients is at least one year.
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Dose Level #2 (4mg MLN9708) | 34 |
One-Year Overall Survival at the Recommended Phase II Dose (RP2D)
Overall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. (NCT02119468)
Timeframe: Date of first dose of study drug to date of death from any cause, up to 24 months. And the median follow-up for the surviving patients is at least one year.
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Dose Level #2 (4mg MLN9708) | 82 |
Overall Response Rate at the Recommended Phase II Dose (RP2D)
Over response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR) or partial remission [PR]) per modified IMWG criteria. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. The exact 95% confidence intervals are calculated for the estimate. (NCT02119468)
Timeframe: From the initial treatment to 24 months
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Dose Level #2 (4mg MLN9708) | 48 |
Maximum Tolerated Dose (MTD) of MLN9708 (Phase I)
The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in Cycle #1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I. (NCT02119468)
Timeframe: From the initial treatment to Day 28 (Cycle #1)
| Intervention | mg (Number) |
|---|
| Dose Level #2 (4mg MLN9708) | 4 |
Clinical Benefit Response Rate at the Recommended Phase II Dose (RP2D)
Clinical benefit response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR), partial remission (PR), minimal response (MR) or stable disease (SD) per modified IMWG criteria. The exact 95% confidence intervals are calculated for the estimate. (NCT02119468)
Timeframe: From the initial treatment up to 24 months
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Dose Level #2 (4mg MLN9708) | 76 |
Duration of Response at the Recommended Phase II Dose (RP2D)
Time from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. (NCT02119468)
Timeframe: Time interval from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first, up to 24 months
| Intervention | Months (Median) |
|---|
| Dose Level #2 (4mg MLN9708) | 9.2 |
Number of Patients With Dose-Limiting Toxicities (Phase I)
Dose Limiting Toxicity (DLT) is defined as any of the toxicities in Section 7.3 that are at least possibly related to either Pomalidomide or MLN9708 that occur during cycle 1. Toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in course 1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I. (NCT02119468)
Timeframe: From the initial treatment to Day 28 (Cycle #1)
| Intervention | Participants (Count of Participants) |
|---|
| Dose Level #1: 3mg MLN9708 | 1 |
| Dose Level #2: 4mg MLN9708 | 1 |
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 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: 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, 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: 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: 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: 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 |
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 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 |
PD-LI Expression On Myeloma Cells
The identification of a biomarker for response by evaluating PD-1/PDL-1 expression in patients' bone marrow aspirate samples will be analyzed in order to help select patients for future anti-PD-1 therapy. The main exploratory biomarker analysis was to examine potential correlation between expression of PD-1 on T cells and PD-L1 on myeloma cells with clinical outcome using the following parameters: response rate focusing on responses ≥ very good partial response (VGPR) and PFS. SAS software (v.9.4; SAS Institute, Inc, Cary, NC) was used for statistical analyses. (NCT02289222)
Timeframe: Tissue sample collection will take place before starting study therapy with MK-3475 at baseline and again at time of relapse as defined by the International Myeloma Working Group Response Criteria (Average of up to 24months)
| Intervention | Participants (Count of Participants) |
|---|
| Negative | Weak Positive | Positive |
|---|
| Pomalidomide, Dexamethasone & MK-3475 | 10 | 6 | 13 |
Time to Progression Free Survival (PFS)
PFS will be measured in all participants. Survival and PFS functions were estimated using the Kaplan-Meier method. The Cox regression model was used to assess the following plausible risk factors for OS and PFS: age, isotype, number of cycles of therapy, and cytogenetic profile. (NCT02289222)
Timeframe: PFS assessments will take place after starting study therapy with MD-3475 and will continue until the start of a new anti-neoplastic therapy, disease progression, death, or the end of study up to an average of 24 months.
| Intervention | Months (Median) |
|---|
| Pomalidomide, Dexamethasone & MK-3475 | 17.4 |
The Number of Participants With Adverse Events
Establish the safety and tolerability of Pomalidomide and Dexamethasone in combination with MK-3475 (NCT02289222)
Timeframe: 24 month
| Intervention | Participants (Count of Participants) |
|---|
| Pomalidomide, Dexamethasone & MK-3475 | 48 |
Extramedullary Response Rate
Extramedullary response, defined as a response by extramedullary plasmacytoma or plasma cell count parameters. The extramedullary response rate will be estimated by the number of responders(patients that achieved a partial or complete response) divided by the number of evaluable patients. Exact binomial confidence intervals will be calculated. (NCT02547662)
Timeframe: 4 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone) | 0.40 |
Biochemical Response Rate
The biochemical response rate will be estimated by the number of responders(patients that achieved partial or complete response) divided by the number of evaluable patients who have measurable disease by serum M-protein, urine M-protein, or serum FLC assay at baseline. Exact binomial confidence intervals will be calculated. (NCT02547662)
Timeframe: 4 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone) | 0.25 |
Confirmed Response Rate
A confirmed response is defined as a patient who has achieved a stringent complete response (sCR), complete response (CR), very good partial response (PR), or PR on two consecutive evaluations. The proportion of successes will be estimated 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 according to the approach of Duffy and Santner. 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. (NCT02547662)
Timeframe: 4 years
| Intervention | proportion of patients (Number) |
|---|
| Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone) | 0.06 |
Progression-free Survival
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. (NCT02547662)
Timeframe: 4 years 8 months
| Intervention | Months (Median) |
|---|
| Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone) | 4.5 |
Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Number of patients with adverse events is reported here, the full list of those adverse events and their frequency is reported in the adverse event section. (NCT02547662)
Timeframe: 4 years 1 month
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Ixazomib Citrate, Pomalidomide, Dexamethasone) | 17 |
Clinical Benefit Response (CBR)
The clinical benefit response, defined as the proportion of subjects achieving a best overall response of MR or better per investigator assessment per IMWG at or prior to initiation of subsequent anticancer therapy. (NCT02548962)
Timeframe: 14 Months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1: Dose Finding (560mg) | 4 |
| Phase 1: Dose Finding (840mg) | 2 |
Duration of Response (DOR)
The time interval between the date of initial documentation of a response and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects not progressed/died. The censoring date is the last adequate tumor assessment date. (NCT02548962)
Timeframe: 14 Months
| Intervention | Months (Median) |
|---|
| Phase 1: Dose Finding (560 mg) | 6.5 |
| Phase 1: Dose Finding (840 mg) | 7.3 |
Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment
The overall response rate, defined as the proportion of subjects achieving a best overall response of PR or better per investigator assessment per IMWG at or prior to initiation of subsequent anticancer therapy (NCT02548962)
Timeframe: 14 Months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1: Dose Finding (560mg) | 3 |
| Phase 1: Dose Finding (840mg) | 1 |
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
ORR was defined as the percentage of the participants in the analysis population 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 database cutoff date was July 9, 2018. (NCT02576977)
Timeframe: Up to approximately 30 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 37.3 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 42.4 |
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Disease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. 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 FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; 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. (NCT02576977)
Timeframe: Up to approximately 30 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 88.1 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 84.8 |
Overall Survival (OS)
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020. (NCT02576977)
Timeframe: Up to approximately 54 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 21.0 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 39.6 |
Participants Discontinuing Study Investigational Product Due to an AE
An adverse event 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. Database cutoff was August 3, 2020. (NCT02576977)
Timeframe: Up to approximately 54 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 26 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 10 |
Participants Experiencing One or More Adverse Events (AEs)
An adverse event (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. Database cutoff was August 3, 2020. (NCT02576977)
Timeframe: Up to approximately 54 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 122 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 119 |
Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria
Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG criteria based on the 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. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018. (NCT02576977)
Timeframe: Up to approximately 30 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab+Pomalidomide+Dexamethasone | 5.7 |
| Standard of Care (SOC) Pomalidomide+Dexamethasone | 7.4 |
Progression Free Survival (PFS)
"PFS is defined as the time from first dosing date to the date of the first documented progression or death due to any cause, whichever occurs first.~Progression is determined per International Myeloma Working Group (IMWG) uniform criteria.~Participants who die without a reported prior progression were considered to have progressed on the date of their death.~Participants who did not progress or die were censored on the date of their last evaluable assessment. Participants who did not have any on study efficacy assessments and did not die were censored on the first dosing date.~Participants who switched to subsequent therapy prior to documented progression were censored on the date of the last evaluable assessment prior to the initiation of the new therapy." (NCT02612779)
Timeframe: From first dose to study completion date (up to approximately 50 months)
| Intervention | Months (Median) |
|---|
| EPd Cohort | 11.1 |
,| EN Cohort | 1.9 |
Objective Response Rate (ORR)
ORR is defined as the percent of participants with best overall response of partial response (PR) or better. Response is determined per IMWG uniform criteria. (NCT02612779)
Timeframe: From first dose to study completion date (up to approximately 50 months)
| Intervention | Percent of Participants (Number) |
|---|
| EN Cohort | 16.7 |
,| EPd Cohort | 51.5 |
Overall Survival (OS)
OS is defined as the time from first dosing date to the date of death from any cause. (NCT02612779)
Timeframe: From first dose to study completion date (up to approximately 50 months)
| Intervention | Months (Median) |
|---|
| EPd Cohort | 41.2 |
| EN Cohort | NA |
Overall Survival (OS)
OS is the time from randomization to the date of death from any cause. The survival time for participants who had not died was censored at the last known alive date. OS was censored at the date of randomization for subjects who were randomized but had no follow-up. (NCT02654132)
Timeframe: From randomization to death (up to approximately 52 months)
| Intervention | Months (Median) |
|---|
| E-Pd Cohort | 29.80 |
| Pd Cohort | 17.41 |
Progression Free Survival (PFS)
"PFS is defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Progressive disease response criteria were defined as an increase of 25% from lowest response value in any one or more of the following:~1. Serum M-component and/or 2. Urine M-component and/or 3. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels 4. Bone marrow plasma cell percentage; 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 that can be attributed solely to the plasma cell proliferative disorder" (NCT02654132)
Timeframe: From randomization to date of progression or death (up to approximately 21 months)
| Intervention | Months (Median) |
|---|
| E-Pd Cohort | 10.25 |
| Pd Cohort | 4.70 |
Objective Response Rate (ORR)
"ORR is defined as the percentage of participants who achieved a best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) using the modified International Myeloma Working Group (IMWG) criteria described as follows, as per investigator's assessment~CR: Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow~sCR: CR, as defined above, plus the following: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence~VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein level plus urine M-protein level < 100 mg per 24 hour~PR: >= 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90% or to < 200 mg per 24 hour." (NCT02654132)
Timeframe: From first dose to disease progression (up to approximately 21 months)
| Intervention | Percent of participants (Number) |
|---|
| E-Pd Cohort | 58.3 |
| Pd Cohort | 24.6 |
Time to Objective Response (TTR)
"The time from the date of randomization to the date of the first stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).~sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry.~CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates.~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 h.~PR = >/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by >/= 90% or to < 200 mg per 24 h." (NCT02726581)
Timeframe: From the date of randomization to the date of the first sCR, CR, VGPR, or PR (up to approximately 64 months)
| Intervention | Months (Mean) |
|---|
| Arm A: N-Pd | 5.91 |
| Arm B: Pd | 4.37 |
Overall Survival (OS)
The time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive. (NCT02726581)
Timeframe: From randomization to the date of death due to any cause (up to approximately 64 months)
| Intervention | Months (Median) |
|---|
| Arm A: N-Pd | 24.87 |
| Arm B: Pd | 21.39 |
Progression Free Survival (PFS)
Randomization to first documented tumor progression or death due to any cause, whichever occurred first. Participants who die without reported prior progression are considered to have progressed on date of their death. Participants who did not progress or die will be censored at their last efficacy assessment. Participants who did not have on study efficacy assessments and alive will be censored on randomization date. Participants who started subsequent anti-cancer therapy without prior reported progression will be censored at last efficacy assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), >/= 50% increase from nadir in SPD of > 1 lesion, or >/= 50% increase in the longest diameter of a previous lesion > 1 cm in short axis. (NCT02726581)
Timeframe: From randomization to the date of the first documented tumor progression or death due to any cause, whichever occurred first (Up to approximately 64 month)
| Intervention | Months (Median) |
|---|
| Arm A: N-Pd | 8.38 |
| Arm B: Pd | 7.33 |
Objective Response Rate (ORR)
"The percentage of randomized participants who achieved a best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using International Myeloma Working Group (IMWG) criteria.~sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry.~CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates.~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 h.~PR = >/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by >/= 90% or to < 200 mg per 24 h." (NCT02726581)
Timeframe: From randomization up to approximately 64 months
| Intervention | Percentage of participants (Number) |
|---|
| Arm A: N-Pd | 48.0 |
| Arm B: Pd | 54.9 |
Duration of Objective Response (DOR)
The time between the date of first response to the date of the first objectively documented tumor progression as assessed by the investigator according to International Myeloma Working Group (IMWG) criteria or death due to any cause prior to subsequent anti-cancer therapy. Participants who neither progress nor die will be censored on the date of their last tumor assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), >/= 50% increase from nadir in SPD of > 1 lesion, or >/= 50% increase in the longest diameter of a previous lesion > 1 cm in short axis. (NCT02726581)
Timeframe: From randomization to the date of the first objectively documented tumor progression or death due to any cause prior to subsequent anti-cancer therapy (up to approximately 64 months)
| Intervention | Months (Median) |
|---|
| Arm A: N-Pd | 8.51 |
| Arm B: Pd | 6.47 |
Time-To-Response (TTR)
Time-to-response is calculated as the time from enrollment to the first date of documented response (partial response or better). Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg per 24 hours. For those participants where POM + DEX were added, time-to-response was calculated from the date POM and DEX were added to the first date of documented response (PR or better). (NCT02807454)
Timeframe: From enrollment to earliest documented response (up to approximately 66 months)
| Intervention | Weeks (Median) |
|---|
| Simon Stage 1: D2 Arm | 4.29 |
| Simon Stage 1: D2 + Pomalidomide + Dexamethasone | 5.07 |
| PD3 Arm | 8.14 |
Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm
Pharmacokinetics of Durvalumab derived from serum concentration versus time data. (NCT02807454)
Timeframe: Cycle 1 - Days 2, 8, 15, 22
| Intervention | Hour (Median) |
|---|
| Simon Stage 1: D2 Arm | 1.150 |
Number of Participants With Serious Adverse Events (SAEs)
Number of participants who experienced at least one serious adverse event. An SAE is any AE occurring at any dose that 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. (NCT02807454)
Timeframe: From first dose to 90 days after last dose (up to approximately 58 months)
| Intervention | Participants (Count of Participants) |
|---|
| Simon Stage 1: D2 Arm | 17 |
| PD3 Arm | 2 |
Number of Participants With Adverse Events (AEs)
Number of participants who experienced at least one adverse event. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant 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, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition should be considered an AE. (NCT02807454)
Timeframe: From first dose to 90 days after last dose (up to approximately 58 months)
| Intervention | Participants (Count of Participants) |
|---|
| Simon Stage 1: D2 Arm | 31 |
| PD3 Arm | 5 |
Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm
Pharmacokinetics of Durvalumab derived from serum concentration versus time data. (NCT02807454)
Timeframe: Cycle 1 - Days 2, 8, 15, 22
| Intervention | ug/mL (Geometric Mean) |
|---|
| Simon Stage 1: D2 Arm | 315.806 |
Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm
Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h). (NCT02807454)
Timeframe: From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
| Intervention | Months (Median) |
|---|
| Simon Stage 1: D2 Arm | 5.74 |
| Simon Stage 1: D2 + Pomalidomide + Dexamethasone | 8.05 |
Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm
Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h). (NCT02807454)
Timeframe: From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
| Intervention | Months (Median) |
|---|
| PD3 Arm | 9.02 |
Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm
Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg per 24 hours. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h). (NCT02807454)
Timeframe: From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
| Intervention | Months (Median) |
|---|
| Simon Stage 1: D2 Arm | 8.31 |
| Simon Stage 1: D2 + Pomalidomide + Dexamethasone | 8.41 |
Overall Response Rate (ORR)
Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. ORR was calculated as the percent of responders (multiplied by 100). Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg per 24 hours. (NCT02807454)
Timeframe: From first dose to up to approximately 66 months
| Intervention | Percentage of participants (Number) |
|---|
| Simon Stage 1: D2 Arm | 53.1 |
| PD3 Arm | 75.0 |
Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm
Pharmacokinetics of Durvalumab derived from serum concentration versus time data. (NCT02807454)
Timeframe: Cycle 1 - Days 2, 8, 15, 22
| Intervention | Hour*ug/mL (Geometric Mean) |
|---|
| Simon Stage 1: D2 Arm | 77831.751 |
Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Simon Stage 1: D2 Arm
Pharmacokinetics of Durvalumab derived from serum concentration versus time data. (NCT02807454)
Timeframe: Cycle 1 - Days 2, 8, 15, 22
| Intervention | Hour*ug/mL (Geometric Mean) |
|---|
| Simon Stage 1: D2 Arm | 83966.099 |
Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm
Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease progression as determined by the investigator. Participants who are alive or lost to follow-up will be censored on the last-known-to-be-alive date. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg per 24 hours. (NCT02807454)
Timeframe: From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
| Intervention | Months (Median) |
|---|
| PD3 Arm | 7.62 |
Time to Progression (TTP) as Per Independent Response Committee
TTP was defined as time from randomization to the date of first documentation of PD, as determined by the IRC. As per IMWG criteria, PD was defined for participants with increase of >= 25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >= 0.5 g/dL), serum M-protein increase >=1 g/dL if the lowest M component was >=5 g/dL; urine M-component (the absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 7.75 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 12.71 |
Time to First Response (TT1R) as Per Independent Response Committee
TT1R was defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required. (NCT02990338)
Timeframe: From the date of randomization to the date of first IRC determined response, or death or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 3.02 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 1.94 |
Time to Best Response (TTBR) as Per Independent Response Committee
TTBR was defined as the time from randomization to the date of first occurrence of IRC determined BOR (PR or better) that was subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. (NCT02990338)
Timeframe: From the date of randomization to date of first occurrence of IRC determined best overall response or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 5.06 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 4.30 |
Progression Free Survival in High Risk Cytogenetic Population
PFS in high risk cytogenetic population was defined as PFS in subgroup of participants carrying high risk cytogenetic changes including del(17p), translocation (t)(4;14) or translocation t(14;16) assessed by fluorescence in situ hybridization (FISH). PFS was defined as the time from date of randomization to date of first documentation of PD (determined by IRC) or date of death from any cause, whichever comes first. PD defined as per IMWG criteria as: increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1 g/dL if lowest M component was >=5 g/dL; urine M-component (absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of previous lesion >1 centimeter (cm) in short axis. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 3.745 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 7.491 |
Progression Free Survival (PFS)
PFS:time from date of randomization to date of first documentation of progressive disease (PD) determined by Independent Response Committee (IRC) or date of death from any cause, whichever comes first. If progression or death was not observed, participant was censored at date of last progression-free tumor assessment prior to study cut-off date. Analysis was performed by Kaplan-Meier method. PD as per International Myeloma Working Group (IMWG) criteria was defined as increase of >=25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >=0.5gram(g)/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL; urine M-component (absolute increase must be >=200mg/24hour), appearance of new lesion(s),>=50% increase from nadir in sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 6.47 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 11.53 |
Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee
VGPR rate was defined as the percentage of participants achieving a VGPR or better as BOR. VGPR was 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 <100 mg/24 h or >=90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment, or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 8.5 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 31.8 |
Overall Survival (OS): Final Analysis
OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first. This pre-specified final analysis was performed when the 220 OS events were met. (NCT02990338)
Timeframe: From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 17.71 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 24.57 |
Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC)
ORR (IMWG criteria): percentage of participants with stringent complete response(sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) as best overall response, assessed by IRC. sCR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates plus normal free light chain(FLC)ratio(0.26-1.65), absence of clonal cells in bone marrow biopsy.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.VGPR: serum and urine M-protein detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h/,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h,if present at baseline,>=50% reduction in the size (SPD) of soft tissue plasmacytomas. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 35.3 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 60.4 |
Duration of Response (DOR) as Per Independent Response Committee
DOR:time from date of first IRC determined response(PR or better) to date of first IRC-PD or death, whichever occurred first.DOR was determined only for participants who had achieved a response of PR or better based on disease assessment by IRC.If progression or death was not observed,participant was censored at date of participants last progression-free tumor assessment prior to initiation of further anti-myeloma treatment(if any)and study cut-off date. PD(IMWG criteria):increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL;urine M-component (absolute increase must be >=200mg/24 hour),appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion,or >=50% increase in the longest diameter of a previous lesion >1 cm in short axis. PR:>=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h. (NCT02990338)
Timeframe: From the date of the first IRC determined response to the date of first IRC progression or death, whichever occurred first (maximum duration 76.7 weeks)
| Intervention | months (Median) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 11.07 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 13.27 |
Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee
CBR was defined as the percentage of participants achieving a MR or better as BOR. MR was defined as >= 25% but <= 49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%, which still exceed 200 mg/24h; if present at baseline, >=50% reduction in size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. (NCT02990338)
Timeframe: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Pd (Pomalidomide + Dexamethasone) | 46.4 |
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 66.9 |
Number of Participants With Anti-drug Antibodies (ADA)
ADA were categorized as: pre-existing, treatment induced and treatment boosted response. Pre-existing ADA was defined as ADA that were present in samples drawn during the pretreatment period (i.e., before the first isatuximab administration). Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without preexisting ADA, including participants without pretreatment samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment and post-treatment. (NCT02990338)
Timeframe: From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Pre-existing ADA | Treatment induced ADA | Treatment boosted ADA |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 0 | 0 | 0 |
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS)
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 utility index (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. (NCT02990338)
Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
| Intervention | centimeter (Mean) |
|---|
| Baseline | Day 1: Cycle 3 | Day 1: Cycle 6 | Day 1: Cycle 9 | Day 1: Cycle 17 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 66.62 | 0.92 | 1.19 | 1.96 | -3.00 |
,| Pd (Pomalidomide + Dexamethasone) | 65.38 | 0.26 | 2.49 | 4.42 | -1.70 |
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value
The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health and wellbeing. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale (for the 5L version). The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state. (NCT02990338)
Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Day 1: Cycle 3 | Day 1: Cycle 6 | Day 1: Cycle 9 | Day 1: Cycle 17 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 0.71 | -0.01 | -0.00 | -0.01 | -0.01 |
,| Pd (Pomalidomide + Dexamethasone) | 0.70 | -0.01 | 0.02 | -0.03 | -0.02 |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Side effects of treatment domain is one of the four domain scores. Side effects of treatment domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale, where higher scores = more side effects and lower HRQL and lower scores = less side effects and better HRQL. (NCT02990338)
Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Day 1: Cycle 3 | Day 1: Cycle 6 | Day 1: Cycle 9 | Day 1: Cycle 17 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 15.60 | 2.61 | 2.11 | 3.14 | 3.02 |
,| Pd (Pomalidomide + Dexamethasone) | 17.49 | 1.69 | -0.13 | 1.43 | -2.93 |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Disease symptoms domain is one of the four domain scores. Disease symptoms domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL (NCT02990338)
Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Day 1: Cycle 3 | Day 1: Cycle 6 | Day 1: Cycle 9 | Day 1: Cycle 17 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 24.12 | -2.07 | -3.30 | -4.66 | 0.00 |
,| Pd (Pomalidomide + Dexamethasone) | 24.91 | -3.79 | -4.08 | -2.83 | -3.33 |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score
EORTC-Quality of Life Questionnaire (QLQ)-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. EORTC QLQ-C30 included GHS/ QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant. (NCT02990338)
Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Day 1: Cycle 3 | Day 1: Cycle 6 | Day 1: Cycle 9 | Day 1: Cycle 17 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 60.10 | -1.22 | -0.16 | 0.41 | -1.92 |
,| Pd (Pomalidomide + Dexamethasone) | 61.19 | -1.45 | -0.12 | 1.06 | -9.17 |
PK Parameter: Plasma Concentration of Isatuximab at Ctrough
Trough Concentration (Ctrough) is the concentration prior to study drug administration. (NCT02990338)
Timeframe: Pre-infusion on C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1; End of treatment (EOT [30 days after last drug administration])
| Intervention | mcg/mL (Geometric Mean) |
|---|
| C1D1 | C1D8 | C1D15 | C1D22 | C2D1 | C2D15 | C3D1 | C3D15 | C4D1 | C4D15 | C5D1 | C6D1 | C7D1 | C8D1 | C9D1 | C10D1 | C11D1 | C12D1 | C13D1 | C14D1 | C15D1 | C16D1 | C17D1 | C18D1 | C19D1 | C20D1 | EOT |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 0.00 | 31.49 | 57.89 | 84.82 | 89.09 | 89.35 | 64.15 | 91.73 | 86.05 | 105.42 | 106.08 | 111.33 | 134.14 | 146.15 | 162.84 | 145.86 | 169.39 | 182.32 | 215.85 | 214.88 | 253.61 | 206.60 | 242.79 | 216.70 | 240.36 | 164.07 | 9.51 |
PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough)
Accumulation Ratio was defined as the ratio of Ctrough of Cycle 2 Day 1 versus Cycle 1 Day 8 and Cycle 4 Day 1 versus Cycle 1 Day 8, where Ctrough is the concentration prior to study drug administration. (NCT02990338)
Timeframe: Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1
| Intervention | ratio (Geometric Mean) |
|---|
| C2D1 versus C1D8 | C4D1 versus C1D8 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 2.689 | 2.620 |
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI)
CEOI was defined as the plasma concentration at end of infusion. (NCT02990338)
Timeframe: End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1
| Intervention | microgram per milliliter (mcg/mL) (Geometric Mean) |
|---|
| End of infusion: C1D1 | End of infusion: C1D15 | End of infusion: C2D1 | End of infusion: C4D1 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 163.05 | 269.20 | 299.85 | 279.31 |
Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour)
CEOI+1 hour was defined as the plasma concentration of isatuximab at 1 hour after end of infusion. (NCT02990338)
Timeframe: Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1
| Intervention | mcg/mL (Geometric Mean) |
|---|
| C1D1 | C4D1 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 171.55 | 294.96 |
Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI)
Accumulation Ratio was defined as the ratio of CEOI of Cycle 2 Day 1 versus Cycle 1 Day 1 and Cycle 4 Day 1 versus Cycle 1 Day 1, where CEOI was the plasma concentration at the end of infusion. (NCT02990338)
Timeframe: End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1
| Intervention | ratio (Geometric Mean) |
|---|
| C2D1 versus C1D1 | C4D1 versus C1D1 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 1.860 | 1.777 |
Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee
BOR:best sequential response from start of treatment until disease progression, death, initiation of further anti-myeloma treatment/data cut-off, whichever comes first. Ordering of evaluations from best to worse was: sCR,CR,VGPR,PR, minimal response (MR), stable disease (SD), PD, and not evaluable.CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates. sCR:CR as defined previously plus normal FLC ratio (0.26 to 1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum and urine M-protein detectable by immunofixation,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h. MR:>=25% but <=49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%. SD: Not meeting criteria for CR,VGPR,PR,MR/PD. (NCT02990338)
Timeframe: From the date of randomization until disease progression, or death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Stringent complete response | Complete response | Very good partial response | Partial response | Minimal response | Stable disease | Progressive Disease | Not evaluable |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 0 | 4.5 | 27.3 | 28.6 | 6.5 | 21.4 | 3.9 | 4.5 |
,| Pd (Pomalidomide + Dexamethasone) | 0.7 | 1.3 | 6.5 | 26.8 | 11.1 | 29.4 | 9.2 | 10.5 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). An SAE is any untoward medical occurrence that at any dose: 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, is a medically important event. (NCT02990338)
Timeframe: From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any treatment emergent SAE | Any TEAE leading to treatment discontinuation |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 151 | 112 | 19 |
,| Pd (Pomalidomide + Dexamethasone) | 146 | 91 | 22 |
Number of Participants With Minimal Residual Disease (MRD)
MRD was assessed by next-generation sequencing in bone marrow samples from participants who achieved CR, to determine the depth of response at the molecular level. IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. MRD was classified as positive or negative at the minimum sensitivity of 1 in 10^5 nucleated cells. MRD negativity was defined as the absence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening. MRD positivity was defined as the presence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening. (NCT02990338)
Timeframe: Up to 76.7 weeks
| Intervention | Participants (Count of Participants) |
|---|
| MRD negative:1 in 10^4 | MRD negative:1 in 10^5 | MRD negative:1 in 10^6 | MRD positive:1 in 10^4 | MRD positive:1 in 10^5 | MRD positive:1 in 10^6 |
|---|
| IPd (Isatuximab + Pomalidomide + Dexamethasone) | 10 | 8 | 2 | 4 | 6 | 9 |
,| Pd (Pomalidomide + Dexamethasone) | 0 | 0 | 0 | 2 | 2 | 2 |
Complete Response Rate (CRR)
"Complete response rate (CRR) will be defined as the proportion of evaluable patients meeting the criteria complete (CR) or stringent complete response (sCR)~Stringent complete response (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~Complete response (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~Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR." (NCT03030261)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Elotuzumab + Pomalidomide + Dexamethasone | 12 |
Event-free Survival (EFS) Rate
-Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment. (NCT03030261)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Elotuzumab + Pomalidomide + Dexamethasone | 13 |
Overall Response Rate (ORR)
-Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). (NCT03030261)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Elotuzumab + Pomalidomide + Dexamethasone | 18 |
Safety and Tolerability: Number of Patients With Treatment-emergent Adverse Events, Including Clinical Laboratory and Vital Signs Abnormalities, as Assessed by CTCAE v4.0
Number of patients with treatment-emergent adverse events, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 will be presented. No formal statistical analysis will be performed for safety endpoints. (NCT03151811)
Timeframe: From start of dosing until 30 days after the last dose of study treatment, the median time frame for study treatment was 25.1 and 22.1 months for Arm A and B, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Melflufen+Dexamethasone | 226 |
| Arm B: Pomalidomide+Dexamethasone | 241 |
Duration of Response (DOR)
DOR defined as the duration in months from first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause. (NCT03151811)
Timeframe: From first evidence of response until confirmed progression, or if no progression, 24 months after end of treatment
| Intervention | months (Median) |
|---|
| Arm A: Melflufen+Dexamethasone | 11.17 |
| Arm B: Pomalidomide+Dexamethasone | 11.07 |
Overall Response Rate (ORR)
ORR defined as the proportion of patients for whom the best overall confirmed response is stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by IRC. (NCT03151811)
Timeframe: From randomization until best response achieved before confirmed progression, or if no progression up to 24 months after end of treatment. Median time to best response was 2.1 and 2.0 months for Arm A and B, respectively.
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Melflufen+Dexamethasone | 80 |
| Arm B: Pomalidomide+Dexamethasone | 67 |
Progression Free Survival (PFS)
Progression Free Survival defined as the duration in months from randomization until first evidence of confirmed disease progression, as assessed by the Independent Review Committee (IRC) according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (NCT03151811)
Timeframe: From randomization to time of progression, or, if no progression, 24 months after end of treatment
| Intervention | months (Median) |
|---|
| Arm A: Melflufen+Dexamethasone | 6.83 |
| Arm B: Pomalidomide+Dexamethasone | 4.93 |
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause, up to 3 years are reported. (NCT03170882)
Timeframe: From date of randomization to death due to any cause (Up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | NA |
| Ixazomib 4 mg + Dexamethasone 20 mg | 18.8 |
HRQOL Based on EORTC QLQ-C30 SubScale Score
The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
| Intervention | score on a scale (Mean) |
|---|
| Global Health Status/QoL: Baseline | Global Health Status/QoL: End of Treatment | Role (Functional Scale): Baseline | Role (Functional Scale): End of Treatment | Emotional (Functional Scale): Baseline | Emotional (Functional Scale): End of Treatment | Cognitive(Functional Scale): Baseline | Cognitive (Functional Scale): End of Treatment | Social (Functional Scale): Baseline | Social (Functional Scale): End of Treatment | Fatigue (Symptom Scale): Baseline | Fatigue (Symptom Scale): End of Treatment | Nausea/Vomiting (Symptom Scale): Baseline | Nausea/Vomiting (Symptom Scale): End of Treatment | Pain (Symptom Scale): Baseline | Pain (Symptom Scale): End of Treatment | Dyspnea (Symptom Scale): Baseline | Dyspnea (Symptom Scale): End of Treatment | Insomnia (Symptom Scale): Baseline | Insomnia (Symptom Scale): End of Treatment | Appetite Loss (Symptom Scale): Baseline | Appetite Loss (Symptom Scale): End of Treatment | Constipation (Symptom Scale): Baseline | Constipation (Symptom Scale): End of Treatment | Diarrhea (Symptom Scale): Baseline | Diarrhea (Symptom Scale): End of Treatment | Financial Difficulties (Symptom Scale): Baseline | Financial Difficulties (Symptom Scale): End of Treatment |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 60.8 | 48.2 | 67.9 | 49.2 | 83.1 | 72.8 | 84.0 | 77.4 | 75.7 | 69.8 | 61.0 | 50.3 | 94.8 | 92.9 | 65.2 | 53.2 | 19.0 | 24.6 | 29.5 | 29.4 | 14.3 | 23.0 | 11.4 | 19.8 | 16.7 | 16.3 | 17.1 | 12.7 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 57.0 | 47.8 | 67.4 | 47.6 | 74.9 | 67.6 | 79.6 | 69.6 | 72.2 | 63.1 | 60.0 | 50.8 | 96.7 | 88.7 | 61.1 | 51.2 | 25.2 | 40.5 | 32.6 | 36.9 | 22.2 | 34.5 | 13.3 | 25.0 | 17.8 | 19.0 | 22.2 | 16.7 |
HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score
The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 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 4 mg + Dexamethasone 20 mg | 72.4 | 68.9 | 81.4 | 77.8 | 82.9 | 83.7 | 67.5 | 64.0 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 73.2 | 73.5 | 81.0 | 74.4 | 81.5 | 75.0 | 58.8 | 57.9 |
Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score
The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | End of Treatment |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 67.9 | 56.5 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 67.0 | 52.4 |
Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter
Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). (NCT03170882)
Timeframe: Up to approximately 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Hospitalizations | Emergency Room Stays | Outpatient Visits |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 23 | 11 | 32 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 16 | 9 | 29 |
Time to Progression (TTP)
TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of >=25% from nadir in: Serum M-component (increase must be >=0.5 g/dl; Urine M-component (increase must be >=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be >=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. (NCT03170882)
Timeframe: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | 5.1 |
| Ixazomib 4 mg + Dexamethasone 20 mg | 8.4 |
Progression Free Survival (PFS)
PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of >=25 % from nadir in: Serum M component (increase must be >=0.5 gram per deciliter [g/dl]); Urine M-component (increase must be >=200 milligram [mg]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be >=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease. (NCT03170882)
Timeframe: From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | 4.8 |
| Ixazomib 4 mg + Dexamethasone 20 mg | 7.1 |
Percentage of Participants With Overall Response
Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when baseline value >=30% and; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=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. (NCT03170882)
Timeframe: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | 41 |
| Ixazomib 4 mg + Dexamethasone 20 mg | 38 |
Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score
EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions. (NCT03170882)
Timeframe: End of Treatment (Up to 28 cycles, each cycle was of 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Mobility: 1 = I Have no Problems in Walking About | Mobility: 2 = I Have Slight Problems in Walking About | Mobility: 3 = I Have Moderate Problems in Walking About | Mobility: 4 = I Have Severe Problems in Walking About | Mobility: 5 = I am Unable to Walk About | Self-Care: 1 = I Have no Problems Washing or Dressing Myself | Self-Care: 2 = I Have Slight Problems Washing or Dressing Myself | Self-Care: 3 = I Have Moderate Problems Washing or Dressing Myself | Self-Care: 4 = I Have Severe Problems Washing or Dressing Myself | Self-Care: 5 = I am Unable to Wash or Dress Myself | Usual Activities: 1 = I Have no Problems Doing my Usual Activities | Usual Activities: 2 = I Have Slight Problems Doing my Usual Activities | Usual Activities: 3 = I Have Moderate Problems Doing my Usual Activities | Usual Activities: 4 = I Have Severe Problems Doing my Usual Activities | Usual Activities: 5 = I am Unable to do my Usual Activities | Pain/Discomfort: 1 = I Have no Pain or Discomfort | Pain/Discomfort: 2 = I Have Slight Pain or Discomfort | Pain/Discomfort: 3 = I Have Moderate Pain or Discomfort | Pain/Discomfort: 4 = I Have Severe Pain or Discomfort | Pain/Discomfort: 5 = I Have Extreme Pain or Discomfort | Anxiety/Depression: 1 = I Have no Pain or Discomfort | Anxiety/Depression: 2 = I Have no Pain or Discomfort | Anxiety/Depression: 3 = I Have no Pain or Discomfort | Anxiety/Depression: 4 = I Have no Pain or Discomfort | Anxiety/Depression: 5 = I Have no Pain or Discomfort |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 9 | 12 | 11 | 8 | 1 | 21 | 10 | 4 | 4 | 2 | 10 | 9 | 12 | 7 | 3 | 8 | 10 | 15 | 6 | 2 | 19 | 13 | 6 | 1 | 2 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 5 | 6 | 8 | 8 | 0 | 13 | 6 | 5 | 3 | 0 | 4 | 7 | 8 | 7 | 1 | 3 | 5 | 13 | 6 | 0 | 6 | 8 | 11 | 2 | 0 |
Time to Response
Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M-protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when Baseline value >=30% and; if present at Baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=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. (NCT03170882)
Timeframe: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | 1.1 |
| Ixazomib 4 mg + Dexamethasone 20 mg | 2.0 |
HU: Duration of Medical Encounters
Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice). (NCT03170882)
Timeframe: Up to approximately 3 years
| Intervention | days (Median) |
|---|
| Hospitalizations | Emergency Room Stays | Outpatient Visits |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 1.0 | 1.0 | 3.0 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 2.0 | 1.0 | 4.0 |
Duration of Response (DOR)
DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. 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 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. 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. (NCT03170882)
Timeframe: From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Pomalidomide 4 mg + Dexamethasone 40 mg | 14.3 |
| Ixazomib 4 mg + Dexamethasone 20 mg | 14.8 |
HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score
The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life. (NCT03170882)
Timeframe: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | End of Treatment |
|---|
| Ixazomib 4 mg + Dexamethasone 20 mg | 64.4 | 55.9 |
,| Pomalidomide 4 mg + Dexamethasone 40 mg | 59.2 | 46.9 |
Overall Response Rate
Overall response rate is defined as the percentage of randomized subjects who achieve a best response of PR or better using modified IMWG criteria as their best overall response (NCT03180736)
Timeframe: Assessed monthly from Randomization until PD, (approximately up to 3 years)]
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab+Pomalidomide+Dexamethasone | 68.87 |
| Pomalidomide + Dexamethasone | 46.41 |
Time to Next Therapy
Time to next therapy will be defined as the time, in months, from randomization to the date to next anti-neoplastic therapy or death from any cause, whichever comes first. (NCT03180736)
Timeframe: From randomization until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 3 years)
| Intervention | months (Median) |
|---|
| Daratumumab+Pomalidomide+Dexamethasone | 23.23 |
| Pomalidomide + Dexamethasone | 11.83 |
Depth of Response
To assess the depth of response by analyzing the percentage of patients with Minimal Residual Disease (MRD) negativity (<10-5), considering the patients who have achieved CR or better, and patients with suspected CR/sCR. (NCT03180736)
Timeframe: From randomization to disease progression or subsequent antimyeloma therapy, assessed up to approximately 3 years.
| Intervention | percentage of participants (Number) |
|---|
| Daratumumab+Pomalidomide+Dexamethasone | 8.61 |
| Pomalidomide + Dexamethasone | 1.96 |
Comparison of Progression Free Survival Between Treatment Arms
Comparison of Progression Free Survival between treatment arms (Daratumumab /Pomalidomide /Dexamethasone vs Pomalidomide / Dexamethasone)[ Time Frame: Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 3 years)] Progression free survival is defined as the time, in months, from randomization to the date of the first documented PD or death due to any cause, whichever comes first. PD will be assessed by the investigator based on the analysis of serum and urine protein electrophoresis (sPEP and uPEP), serum and urine immunofixation (sIFE and uIFE), serum free light chain protein (sFLC),corrected serum calcium assessment, imaging and bone marrow assessments as per modified IMWG guidelines. (NCT03180736)
Timeframe: Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 3 years)]
| Intervention | months (Median) |
|---|
| Daratumumab+Pomalidomide+Dexamethasone | 12.42 |
| Pomalidomide + Dexamethasone | 6.93 |
Duration of Response
Duration of response will be restricted to the randomized subjects who achieve a best objective response of PR or better. It is measured from the time, in months, that the criteria for objective response are first met until the date of a progression event (according to the primary definition of PFS). (NCT03180736)
Timeframe: From informed consent until 30 days after last study treatment, assessed up to approximately 3 years.
| Intervention | months (Median) |
|---|
| Daratumumab+Pomalidomide+Dexamethasone | NA |
| Pomalidomide + Dexamethasone | 15.90 |
Overall Response Rate
Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, very good partial response (VGPR), or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated. (NCT03202628)
Timeframe: 30 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT) | 50 |
Number of Patients Experiencing Adverse Events Graded According to the Medical Dictionary for Regulatory Activities (MedDRA) Version (v) 12.1
The number of patients experiencing a grade 3 or greater adverse event will be reported. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. (NCT03202628)
Timeframe: 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT) | 7 |
Percentage of Participants With Greater Than or Equal to (>=) Very Good Partial Response (VGPR) Rate
Will be estimated by the number of patients who achieve a stringent complete response (sCR), complete response CR, or VGPR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall >= VGPR will be calculated. (NCT03202628)
Timeframe: 30 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT) | 25 |
Progression-free Survival at 18 Months (PFS18) Defined as the Proportion of Patients Alive and Free From Disease Progression at 18 Months From Study Entry
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated. If patients are censored prior to 18 months post registration, a Kaplan Meier (Kaplan, E. and Meier, P., 1958) estimate for PFS18 along with the 95% confidence intervals will be reported. (NCT03202628)
Timeframe: 18 months
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT) | 0.3750 |
Percent of Patients Alive at 30 Months
The distribution of overall survival will be estimated using the method of Kaplan-Meier. (NCT03202628)
Timeframe: 30 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Ixazomib, Pomalidomide, Dexamethasone, ASCT) | 75 |
Kaplan-Meier Estimate of Progression-Free Survival (PFS)
Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive. (NCT03257631)
Timeframe: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
| Intervention | weeks (Median) |
|---|
| Diffuse Intrinsic Pontine Glioma | 11.29 |
| Ependymoma | 8.43 |
| High-grade Glioma | 7.86 |
| Medulloblastoma | 8.43 |
Percentage of Participants With Long-term Stable Disease
Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or > 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. (NCT03257631)
Timeframe: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
| Intervention | percentage of participants (Number) |
|---|
| Diffuse Intrinsic Pontine Glioma | 0 |
| Ependymoma | 11.1 |
| High-grade Glioma | 5.3 |
| Medulloblastoma | 0 |
Percentage of Participants With an Objective Response or Long-term Stable Disease
Objective response and long-term stable disease rate was defined as the percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. Disease assessments were based on magnetic resonance imaging (MRI) assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. (NCT03257631)
Timeframe: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
| Intervention | percentage of participants (Number) |
|---|
| Diffuse Intrinsic Pontine Glioma | 0 |
| Ependymoma | 11.1 |
| High-grade Glioma | 10.5 |
| Medulloblastoma | 0 |
Percentage of Participants Who Achieved an Objective Response
Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. (NCT03257631)
Timeframe: 6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
| Intervention | percentage of participants (Number) |
|---|
| Diffuse Intrinsic Pontine Glioma | 0 |
| Ependymoma | 0 |
| High-grade Glioma | 5.3 |
| Medulloblastoma | 0 |
Kaplan-Meier Estimate of Duration of Response
Duration of response is defined as the time from the date of the first objective response (complete response or partial response) to disease progression, for participants with a response. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive. (NCT03257631)
Timeframe: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
| Intervention | weeks (Median) |
|---|
| High-grade Glioma | NA |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug. (NCT03257631)
Timeframe: From first dose of pomalidomide until 28 days after the last dose; median treatment duration was 84 days in the DIPG group, 112.0 days in the ependymoma group, 40.5 days in the high-grade glioma group and 57.0 days in the medulloblastoma group.
| Intervention | Participants (Count of Participants) |
|---|
| Any treatment-emergent adverse event (TEAE) | TEAE related to study drug | Serious TEAE | Serious TEAE related to study drug | Grade 3/4 TEAE | Grade 3/4 TEAE related to study drug | TEAE leading to death | TEAE leading to dose reduction | TEAE leading to dose interruption | TEAE leading to study drug discontinuation |
|---|
| Diffuse Intrinsic Pontine Glioma | 11 | 5 | 8 | 1 | 8 | 3 | 5 | 1 | 4 | 2 |
,| Ependymoma | 8 | 7 | 4 | 0 | 6 | 2 | 1 | 0 | 3 | 1 |
,| High-grade Glioma | 21 | 14 | 13 | 6 | 14 | 10 | 3 | 2 | 5 | 2 |
,| Medulloblastoma | 9 | 8 | 4 | 0 | 6 | 4 | 1 | 0 | 2 | 0 |
Kalan-Meier Estimate of Overall Survival
Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive. (NCT03257631)
Timeframe: From the first dose of pomalidomide to the data cut-off date of 15 March 2019; median overall time on follow-up was 4.86 months (3.78, 5.65, 4.04, and 8.38 months in each group respectively).
| Intervention | months (Median) |
|---|
| Diffuse Intrinsic Pontine Glioma | 3.78 |
| Ependymoma | 12.02 |
| High-grade Glioma | 5.06 |
| Medulloblastoma | 11.60 |
Phase 1: RP2D of TAK-079
RP2D was determined by dose escalating monotherapy groups. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | mg (Number) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab | 600 |
Phase 1: Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a partial response (PR) or better during the study. PR is defined as >=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 were not measurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels was required in place of the M-protein criteria. If serum and urine M-protein were not measurable, and serum FLC was also not measurable, ≥50% reduction in bone marrow plasma cells was required in place of M-protein, provided the baseline percentage was ≥30%. In addition to the above criteria, if present at baseline, ≥50% reduction in the size of soft tissue plasmacytomas was also required. Two consecutive assessments were needed; no known evidence of progressive or new bone lesions if radiographic studies were performed. Percentages are rounded off to whole number at the nearest decimal. (NCT03439280)
Timeframe: Up to approximately 3.7 years
| Intervention | percentage of participants (Number) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 25 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 42 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 47 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 33 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 83 |
Phase 1: Number of Participants With TEAEs Leading to Treatment Discontinuation
TEAEs leading to discontinuation were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug leading to discontinuation of any of the study treatment when given in combination. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 2 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 0 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 3 |
Phase 1: Number of Participants With TEAEs Leading to Dose Modifications
TEAEs were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. Dose modification includes dose delayed, reduced, and drug discontinued permanently. Dose reduced includes scenarios where the dose was skipped, held, or missed. Dose modifications also refer to a modification of any drug in the study treatment when given in combination. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 1 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 1 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 1 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 11 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 1 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 6 |
Phase 1: Number of Participants With Serious TEAEs
TEAEs were any untoward medical occurrence (called an AE) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study 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. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 1 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 8 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 1 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 2 |
Phase 1: Number of Participants With Grade 3 or Higher TEAEs
AE Grades were evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 2 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 1 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 3 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 12 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 1 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 6 |
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were defined as any of the following events: Grade 4 laboratory abnormalities, except those events that were clearly due to extraneous causes; nonhematologic TEAEs of grade greater than or equal to (>=3) except grade 3 nausea/vomiting, fatigue lasting less than 72 hours, elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that resolves to grade less than or equal to (<=)1 or baseline within 7 days, injection reaction (IR) that responds to symptomatic treatment; Hematologic TEAEs of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade >=4, except grade >=3 hemolysis, grade 3 low platelet or higher count with clinically meaningful bleeding; and an incomplete recovery from treatment-related toxicity causing a greater than (>) 2-week delay in the next scheduled injection before the initiation of Cycle 2 will be considered a DLT. (NCT03439280)
Timeframe: Cycle 1 (cycle length=28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 0 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 1 |
Phase 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
TEAEs were any untoward medical occurrence (called an adverse event [AE]) that occurred after administration of the first dose of any study drug and through 30 days after the last dose of any study drug. (NCT03439280)
Timeframe: From the first dose of study drug through 30 days after the last dose (up to approximately 3.7 years)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 4 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 3 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 12 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 22 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 3 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 6 |
Percentage of Participants With Positive Anti-drug Antibodies (ADA)
Percentages are rounded off to whole number at the nearest decimal. (NCT03439280)
Timeframe: Up to approximately 3.7 years
| Intervention | percentage of participants (Number) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 8 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 0 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 17 |
Percentage of Participants With Minimal Response (MR)
MR is defined as >=25% but <=49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%. Percentages are rounded off to whole number at the nearest decimal. (NCT03439280)
Timeframe: Up to approximately 3.7 years
| Intervention | percentage of participants (Number) |
|---|
| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 33 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 0 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 11 |
| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 0 |
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 17 |
Cmax: Maximum Observed Serum Concentration for TAK-079
(NCT03439280)
Timeframe: Cycles 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=28 days)
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Week 1 | Cycle 2 Week 1 |
|---|
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 5690 | 25800 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 46000 | 174000 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 1660 | 12900 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 5810 | 42700 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 47.0 | 228 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 21300 | 143000 |
Tmax: Time to Reach the Maximum Observed Serum Concentration (Cmax) for TAK-079
(NCT03439280)
Timeframe: Cycles 1 and 2: Day 1 pre-dose and at multiple time points (up to 190.95 hours) post-dose (cycle length=28 days)
| Intervention | hours (h) (Median) |
|---|
| Cycle 1 Week 1 | Cycle 2 Week 1 |
|---|
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 70.58 | 49.33 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 73.22 | 71.92 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 70.60 | 71.15 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 71.11 | 70.00 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 60.18 | 58.77 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 72.55 | 59.12 |
AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079
(NCT03439280)
Timeframe: Cycle 1 and 2: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=28 days)
| Intervention | hours*nanogram/milliliter (h*ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Week 1 | Cycle 2 Week 1 |
|---|
| Phase 1 Combination Cohort: Mezagitamab 300 mg + PomDex | 603000 | 2690000 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 1200 mg | 5780000 | 27000000 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 135 mg | 160000 | 1920000 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 300 mg | 547000 | 4780000 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 45 mg | 32800 | 10400 |
,| Phase 1 Dose Escalation Cohort: Mezagitamab 600 mg | 2710000 | 19300000 |
Overall Survival (OS)
defined as the time from the date of random disclosure to the date of death from any cause for the comparisons B vs A (NCT03440411)
Timeframe: 57 months
| Intervention | Participants (Count of Participants) |
|---|
| Death | Censored |
|---|
| Arm A | 2 | 2 |
,| Arm B | 0 | 4 |
Duration of Response (DOR)
DOR for a given participant is defined as the number of days from the date of that participant's first documented response (Partial Response [PR] or better) to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant with a documented response did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored. (NCT03567616)
Timeframe: Approximately 15 months
| Intervention | days (Median) |
|---|
| Participants Positive for t(11;14) Translocation | 393.0 |
| Participants Negative for t(11;14) Translocation | NA |
| All Participants | 393.0 |
Progression-Free Survival (PFS)
PFS is defined as the number of days from the date of first dose of any study drug to the date of disease progression or death, whichever occurs first. All disease progression was to be included regardless of whether the event occurred during or after the participant was taking any study drug. (NCT03567616)
Timeframe: Approximately 20 months
| Intervention | days (Median) |
|---|
| Participants Positive for t(11;14) Translocation | 220.0 |
| Participants Negative for t(11;14) Translocation | NA |
| All Participants | 320.0 |
Time-to-progression (TTP)
TTP for a given participant is defined as the number of days from the date of first dose to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored. (NCT03567616)
Timeframe: Approximately 15 months
| Intervention | days (Median) |
|---|
| Participants Positive for t(11;14) Translocation | 420.0 |
| Participants Negative for t(11;14) Translocation | NA |
| All Participants | 420.0 |
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant 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 reasonable possibility or no reasonable possibility. 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 participant 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. (NCT03567616)
Timeframe: From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | TESAE |
|---|
| Participants Negative for t(11;14) Translocation | 5 | 2 |
,| Participants Positive for t(11;14) Translocation | 3 | 3 |
Overall Response Rate (ORR)
ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level + urine M-protein level < 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. (NCT03567616)
Timeframe: Approximately 15 months
| Intervention | percentage of participants (Number) |
|---|
| Participants Positive for t(11;14) Translocation | 66.7 |
| Participants Negative for t(11;14) Translocation | 60.0 |
| All Participants | 62.5 |
Progression-free Survival (PFS) Based on Investigator-assessed Response as Per International Myeloma Working Group (IMWG)
PFS is time from randomization until earliest date of progressive disease (PD), or death due to any cause per investigator-assessed response per IMWG. PD is ≥25% increase from nadir in any of following: serum M-protein (absolute increase ≥0.5 gram per deciliter [g/dL]),urine M-protein(absolute increase ≥200 mg/24hr),difference between involved/uninvolved FLC levels (absolute increase >10 mg/dL) in patients without measurable serum and urine M-protein levels, or bone marrow plasma-cell percentage irrespective of baseline status (absolute increase ≥10%) in patients without measurable serum and urine M-protein levels and without measurable involved FLC levels; appearance of new lesion,≥50% increase in longest diameter of a lesion previously measured >1cm in short axis, or ≥50% increase from nadir in sum of products of two longest perpendicular diameters of more than 1 lesion; ≥50% increase in circulating plasma cells (minimum of 200 cells/microliter) if this is only measure of disease. (NCT04162210)
Timeframe: Up to 27 months
| Intervention | Months (Median) |
|---|
| Belantamab Mafodotin | 11.2 |
| Pomalidomide Plus Dexamethasone | 7.0 |
Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) (PA DCO Only)
Overall response was defined as the best overall confirmed response of: Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to < 200 mg/24-h. Assessment was by IRC per International Myeloma Working Group Uniform Response Criteria (IMWG-URC). The 90% confidence intervals were estimated using the Clopper-Pearson method (1994). (NCT04191616)
Timeframe: From day 1 cycle 1 until the PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib With Pomalidomide and Dexamethasone (KPd) | 57.7 |
Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC (PA DCO Only)
The MRD[-]CR rate was defined as the number of participants who reached MRD[-]CR at the 12 month landmark (8- to 13-month window). MRD[-]CR was defined as the achievement of CR (including sCR or better) per IMWG-URC by IRC assessment and MRD[-] status at a sensitivity of 10^-5 using next-generation sequencing based method in the bone marrow. The 90% CIs were estimated using the Clopper-Pearson method (1994). (NCT04191616)
Timeframe: Day 1 cycle 1 to month 12 (8 to 13 month window). PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Carfilzomib With Pomalidomide and Dexamethasone (KPd) | 3.8 |
Number of Participants With Adverse Events
Adverse events will be determined by Events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The frequency of adverse events will be collected in tabular summary from when a participant consent to study until end of study or patient participant starts a new treatment. (NCT04843579)
Timeframe: Adverse events were collected from time of informed consent until 30 days after the last day of study drug administration for each participant. The maximum period that AEs were collected for a participant was 300 days.
| Intervention | Participants (Count of Participants) |
|---|
| Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd) | 4 |
Percentage of Participants With Overall Response Rate of Partial Response or Better
ORR is defined as participants who experience a partial response, very good partial response, complete response, or stringent complete response per International Myeloma Working Group Criteria (IMWG) 2016 criteria. Complete Response is defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates. Stringent Complete Response is defined as complete response as noted previously plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immune-histochemistry. Partial Response is ≥50% reduction of serum M-protein plus reduction in 24 hour urinary M-protein by ≥90% or to <200 mg per 24 h. Very Good Partial Response 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 hr. (NCT04843579)
Timeframe: Until disease progression; the maximum time any participant was followed for ORR was 287 days
| Intervention | Participants (Count of Participants) |
|---|
| Selinexor, Clarithromycin, Pomalidomide and Dexamethasone (ClaSPd) | 2 |