| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Randomised Controlled Phase-2 Trial to Determine the Efficacy of Adoptive Immunotherapy With Haploidentical Natural Killer Cells in High-risk Acute Myeloid Leukemia[NCT02229266] | Phase 2 | 1 participants (Actual) | Interventional | 2015-09-30 | Terminated(stopped due to low recruitment rate) |
| A Randomized Trial for Adults With Newly Diagnosed Acute Lymphoblastic Leukemia[NCT01085617] | Phase 3 | 1,033 participants (Actual) | Interventional | 2010-12-31 | Active, not recruiting |
| S0919, A Phase II Study of Idarubicin and Ara-C in Combination With Pravastatin for Poor-Risk Acute Myelogenous Leukemia[NCT00840177] | Phase 2 | 115 participants (Actual) | Interventional | 2009-12-10 | Completed |
| Pilot Trial of Hyper-CVAD and Methotrexate/ARA C Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma[NCT00041132] | Phase 2 | 56 participants (Actual) | Interventional | 2002-09-30 | Completed |
| A Phase I/II Pilot Study of Ifosfamide, Carboplatin and Etoposide Therapy (ICE) and SGN-30 (NSC# 731636, IND#) in Children With CD30+ Recurrent Anaplastic Large Cell Lymphoma[NCT00354107] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2007-01-31 | Terminated |
| T-Cell or Natural Killer (NK) Cell Adback in Patients With Lymphoid Malignancies Receiving Allogeneic Stem Cell Transplantation With Campath-IH Containing Conditioning Regimens[NCT00536978] | Phase 2 | 22 participants (Actual) | Interventional | 2007-09-30 | Completed |
| ALinC 17, Classification ©), B-precursor Induction Treatment (I)[NCT01225874] | | 3,762 participants (Actual) | Interventional | 1999-12-31 | Completed |
| Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia[NCT01132586] | Phase 1 | 61 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Study of Low-Dose Cytarabine and Etoposide With or Without All-Trans Retinoic Acid in Older Patients Not Eligible for Intensive Chemotherapy With Acute Myeloid Leukemia and NPM1 Mutation[NCT01237808] | Phase 3 | 144 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Busulfan, Etoposide, Cytarabine and Melphalan (BuEAM) as a Conditioning for Autologous Stem Cell Transplantation in Patients With Diffuse Large B Cell Lymphoma (DLCBL) Previously Treated With Rituximab Based Regimen[NCT01063439] | Phase 2 | 42 participants (Anticipated) | Interventional | 2010-01-31 | Recruiting |
| Randomized Phase-II Trial Evaluating Induction Therapy With Idarubicin and Etoposide Plus Sequential or Concurrent Azacitidine and Maintenance Therapy With Azacitidine[NCT01180322] | Phase 2 | 277 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease[NCT00302003] | Phase 3 | 287 participants (Actual) | Interventional | 2006-02-28 | Completed |
| A Phase I Dose Finding Study Of Panobinostat In Children With Refractory Hematologic Malignancies[NCT01321346] | Phase 1 | 30 participants (Actual) | Interventional | 2011-03-31 | Completed |
| A Master Protocol for Biomarker-Based Treatment of AML (The Beat AML Trial)[NCT03013998] | Phase 1/Phase 2 | 2,000 participants (Anticipated) | Interventional | 2016-11-30 | Recruiting |
| "A Phase III Trial Comparing ARA-C/High-Dose Mitoxantrone (ALL-2') to A Standard Vincristine/Prednisone Based Regimen ('L-20') as Induction Therapy For Adult Patients With Acute Lymphoblastic Leukemia (ALL): The ALL-4 Protocol"[NCT00002766] | Phase 3 | 170 participants (Actual) | Interventional | 1996-03-31 | Completed |
| A Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene Alterations[NCT05521087] | Phase 1 | 80 participants (Anticipated) | Interventional | 2024-05-29 | Not yet recruiting |
| A Phase 1b Study of JNJ-75276617 in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations[NCT05453903] | Phase 1 | 150 participants (Anticipated) | Interventional | 2022-10-04 | Recruiting |
| A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Entospletinib (ENTO) as Monotherapy in Japanese Subjects With Relapsed or Refractory Hematologic Malignancies and in Combination With Chemotherapy in Japanese Subjects With [NCT03135028] | Phase 1 | 9 participants (Actual) | Interventional | 2017-05-19 | Terminated(stopped due to No signal of efficacy with Entospletinib) |
| Leukemia Stem Cell Detection in Acute Myeloid Leukemia[NCT02927938] | Phase 3 | 18 participants (Actual) | Interventional | 2016-09-30 | Terminated(stopped due to Study terminated 7/23/2019 due to limited participation and testing challenges.) |
| An Open Label, Single Arm, Single-Center Exploratory Study to Evaluate the Efficacy and Safety of Selinexor and HAAG +/- HMA in Relapsed/Refractory Acute Leukemia (AML) Patients[NCT05805072] | | 20 participants (Anticipated) | Interventional | 2023-05-01 | Not yet recruiting |
| A Single-arm, Open, Multicenter, Phase II Study to Investigator the Efficacy and Safety of HYML-122 and Cytarabine in Patients With FLT3 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT05241093] | Phase 2 | 18 participants (Anticipated) | Interventional | 2022-03-29 | Recruiting |
| A Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Mitoxantrone Hydrochloride Liposome Injection Combined With Chemotherapy in Previously Untreated de Novo Acute Myeloid Leukemia[NCT05941585] | | 90 participants (Anticipated) | Interventional | 2023-07-31 | Not yet recruiting |
| CLAG-M or FLAG-Ida Chemotherapy Followed Immediately by Related/Unrelated Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1 Study[NCT04375631] | Phase 1 | 120 participants (Anticipated) | Interventional | 2020-12-03 | Recruiting |
| Busulfan, Etoposide, Cytarabine, and Melphalan (BuEAM) as a Conditioning for Autologous Stem Cell Transplantation in Patients With T Cell or NK Cell Lymphoma[NCT01178658] | Phase 2 | 42 participants (Anticipated) | Interventional | 2010-07-31 | Recruiting |
| Multicentric Phase II Trial, Prospective, Open, Single Group, to Discuss Induction Therapy With a Combination of Clofarabine and Low-dose Cytarabine Followed by Consolidation Therapy With Clofarabine and Low-dose Cytarabine for the Treatment of AML Patien[NCT01193400] | Phase 2 | 75 participants (Anticipated) | Interventional | 2010-09-30 | Terminated |
| A Phase I/II Study of Llme Treated Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematological Malignancies[NCT00429416] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2004-03-31 | Completed |
| Prexasertib in Combination With Mitoxantrone, Etoposide and Cytarabine (MEC) in Relapsed/Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) - a Phase I Trial[NCT03735446] | Phase 1 | 2 participants (Actual) | Interventional | 2019-01-18 | Terminated(stopped due to Sponsor Decision) |
| A Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS)[NCT00071799] | Phase 3 | 358 participants (Actual) | Interventional | 2003-11-01 | Completed |
| A Multicenter, Prospective, Non-randomized, Phase I-II Trial to Assess the Efficacy and Safety of the Combination of Oral Quizartinib and the FLAG-IDA Chemotherapy Regimen in First Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients[NCT04112589] | Phase 1/Phase 2 | 63 participants (Actual) | Interventional | 2019-12-26 | Active, not recruiting |
| Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors[NCT00054327] | Phase 2 | 34 participants (Actual) | Interventional | 2000-11-30 | Completed |
| Phase II Study of the Combination of Low-Intensity Chemotherapy and Blinatumomab in Patients With Philadelphia Chromosome Negative Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)[NCT03518112] | Phase 2 | 6 participants (Actual) | Interventional | 2018-04-18 | Terminated(stopped due to Due to Competing Studies) |
| A Phase II Study of R-CHOP With Intensive CNS Prophylaxis and Scrotal Irradiation in Patients With Primary Testicular Diffuse Large B-cell Lymphoma[NCT00945724] | Phase 2 | 54 participants (Actual) | Interventional | 2009-04-30 | Active, not recruiting |
| A Phase 1/2 Study of CPX-351 (NSC# 775341) Alone Followed by Fludarabine, Cytarabine, and G-CSF (FLAG) for Children With Relapsed Acute Myeloid Leukemia (AML)[NCT02642965] | Phase 1/Phase 2 | 38 participants (Actual) | Interventional | 2016-05-02 | Completed |
| Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies[NCT01139151] | Phase 1 | 31 participants (Actual) | Interventional | 2010-08-31 | Completed |
| Phase I Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk, Acute Myelogenous Leukemia (AML)[NCT01265199] | Phase 1 | 29 participants (Actual) | Interventional | 2011-02-28 | Terminated(stopped due to Study was terminated before a MTD was determined for administrative reasons) |
| A Monocenter Prospective Single Arm Study of Cladribine Plus Homoharringtonine and Cytarabine Regimen (CHA) for Induced Therapy in Adults de Novo Acute Myeloid Leukemia (Non-M3)[NCT05906914] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-06-29 | Recruiting |
| Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin Compared To Dexamethasone, Cytarabine, And Cisplatin Plus/Minus Rituximab [(R)-GDP vs (R)-DHAP] As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkin'[NCT00078949] | Phase 3 | 849 participants (Actual) | Interventional | 2003-08-27 | Completed |
| A Phase I and Expansion Cohort Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT03194932] | Phase 1 | 62 participants (Actual) | Interventional | 2017-07-11 | Completed |
| Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil - a Prospective Collaborative Study[NCT05959720] | | 180 participants (Anticipated) | Observational [Patient Registry] | 2023-09-05 | Recruiting |
| A Phase II Randomized Study to Assess the Efficacy on Outcome of Venetoclax Combined With Cytarabine Versus Idarubicin Combined With Cytarabine Administered as Post-remission Therapy to Elderly Patients With Acute Myeloid Leukemia in First Remission[NCT04968015] | Phase 2 | 134 participants (Anticipated) | Interventional | 2022-05-25 | Recruiting |
| Open-Label Phase 2 Trial of Vyxeos in Patients With Intermediate and High-Risk Acute Myeloid Leukemia Who Have Failed an Initial Cycle of Standard Cytarabine and Daunorubicin Chemotherapy[NCT04049539] | Phase 1/Phase 2 | 28 participants (Anticipated) | Interventional | 2021-01-29 | Recruiting |
| Pilot Open-label Trial of Nivolumab Combined With Chemotherapy in Refractory Myelodysplastic Syndromes.[NCT03259516] | Phase 1/Phase 2 | 2 participants (Actual) | Interventional | 2017-05-25 | Terminated(stopped due to Slow recruitment rate) |
| A Phase II, Open-Label Clinical Efficacy Study Defining Genomic Signatures That Correlate With Midostaurin Response in Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT03207334] | Phase 2 | 0 participants (Actual) | Interventional | 2018-11-30 | Withdrawn(stopped due to Insufficient funding) |
| A Multicenter，Open-label，Radonmized Study on the Treatment of Older Adult Acute Myeloid Leukemia Patients Aged 55 to 65 Years Old[NCT02432872] | | 300 participants (Anticipated) | Interventional | 2015-04-30 | Recruiting |
| Prospective Study of Rituximab Combined With Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia[NCT01358253] | Phase 4 | 100 participants (Actual) | Interventional | 2010-12-31 | Completed |
| Phase 1b Study of Venetoclax in Combination With Intensive Induction and Consolidation Chemotherapy in Treatment Naïve Subjects With Acute Myelogenous Leukemia[NCT03709758] | Phase 1 | 64 participants (Anticipated) | Interventional | 2018-10-17 | Recruiting |
| A Randomized Phase 3 Trial of Fludarabine/Cytarabine/Gemtuzumab Ozogamicin With or Without Venetoclax in Children With Relapsed AML[NCT05183035] | Phase 3 | 98 participants (Anticipated) | Interventional | 2022-10-01 | Recruiting |
| A Phase II Study of Ibrutinib Plus Rituximab With Hyper-CVAD Consolidation in Newly Diagnosed Young Patients With Mantle Cell Lymphoma: A Window Period for Bioimmunotherapy Before Chemotherapy[NCT02427620] | Phase 2 | 131 participants (Anticipated) | Interventional | 2015-06-03 | Active, not recruiting |
| A Phase I Study of AC220 for Children With Relapsed or Refractory ALL or AML[NCT01411267] | Phase 1 | 24 participants (Actual) | Interventional | 2011-09-01 | Completed |
| A Phase 2 Study Evaluating Efficacy and Safety of Chi-BEAC Combining With Auto-HSCT to Treat Aggressive Lymphoma Subjects[NCT03629873] | Phase 2 | 69 participants (Anticipated) | Interventional | 2018-02-01 | Active, not recruiting |
| High Dose Chemotherapy With Autologous Stem Cell Rescue for Aggressive B Cell Lymphoma and Hodgkin Lymphoma in HIV-infected Patients (BMT CTN #0803)[NCT01141712] | Phase 2 | 43 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Phase 1 Study of FLAG-Ida With Pivekimab Sunirine (PVEK [IMGN632]) for Adults With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms[NCT06034470] | Phase 1 | 30 participants (Anticipated) | Interventional | 2024-01-13 | Recruiting |
| A Feasibility Trial of MLN4924 (Pevonedistat, TAK 924) Given in Combination With Azacitidine, Fludarabine, and Cytarabine, in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome[NCT03813147] | Phase 1 | 12 participants (Actual) | Interventional | 2019-05-17 | Active, not recruiting |
| A Pilot Trial of Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With DLBCL[NCT03072771] | Phase 1 | 14 participants (Actual) | Interventional | 2017-08-01 | Completed |
| A Phase II Trial of Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD) in Patients With Relapsed CD20+ B-Cell Non-Hodgkins Lymphoma[NCT00166439] | Phase 2 | 50 participants (Actual) | Interventional | 2005-03-31 | Completed |
| Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia[NCT00137111] | Phase 3 | 501 participants (Actual) | Interventional | 2000-07-08 | Completed |
| Cladribine Combined With G-CSF and Cytarabine as a Salvage Treatment in Refractory/Relapsed Acute Lymphoblastic Leukemia[NCT05578378] | Phase 2/Phase 3 | 32 participants (Anticipated) | Interventional | 2022-01-01 | Recruiting |
| Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma[NCT00133991] | Phase 2 | 23 participants (Actual) | Interventional | 2005-07-31 | Completed |
| An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Histone Deacetylase Inhibitor Chidamide Total Therapy for Adult T-lymphoblastic Lymphoma/Leukemia[NCT03564704] | Phase 2/Phase 3 | 80 participants (Anticipated) | Interventional | 2016-02-14 | Recruiting |
| Phase 1b, Open-label, Dose Escalation Study of Quizartinib in Combination With Induction and Consolidation Chemotherapy in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT02834390] | Phase 1 | 7 participants (Actual) | Interventional | 2016-08-12 | Completed |
| A Phase 1 Study of MLN9708 in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML)[NCT02070458] | Phase 1 | 30 participants (Actual) | Interventional | 2014-10-08 | Completed |
| A Phase II Study of Tosedostat in Combination With Either Cytarabine or Decitabine in Newly Diagnosed AML or High-Risk MDS[NCT01567059] | Phase 2 | 34 participants (Actual) | Interventional | 2012-05-31 | Completed |
| An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Histone Deacetylase Inhibitor Chidamide Target Total Therapy for Adult Early T-cell Progenitor Acute Lymphoblastic Leukemia/Lymphoma[NCT03553238] | Phase 2/Phase 3 | 70 participants (Anticipated) | Interventional | 2016-02-14 | Recruiting |
| A Phase 2 Study of Blinatumomab (NSC# 765986) in Combination With Nivolumab (NSC # 748726), a Checkpoint Inhibitor of PD-1, in B-ALL Patients Aged >/= 1 to < 31 Years Old With First Relapse[NCT04546399] | Phase 2 | 550 participants (Anticipated) | Interventional | 2020-12-04 | Suspended(stopped due to Other - FDA Partial Clinical Hold) |
| A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Study of Idasanutlin, an MDM2 Antagonist, With Cytarabine Versus Cytarabine Plus Placebo in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT02545283] | Phase 3 | 447 participants (Actual) | Interventional | 2015-12-30 | Terminated(stopped due to The study was stopped for futility based on efficacy results at the interim analysis; no unexpected safety findings were observed.) |
| Treatment Protocol For All Fragile Patients Ph' Negative Over 55 Years[NCT01358201] | Phase 4 | 100 participants (Anticipated) | Interventional | 2010-05-31 | Recruiting |
| Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)[NCT02255162] | Phase 1 | 8 participants (Actual) | Interventional | 2015-01-31 | Terminated(stopped due to Slow Accrual) |
| Modified TBF Regimen as Conditioning Regimen Prior to Allogeneic Hematopoietic Cell Transplantation for T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma：Phase II Study[NCT05598593] | Phase 2 | 70 participants (Anticipated) | Interventional | 2022-10-23 | Recruiting |
| CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)[NCT04326439] | Phase 2 | 8 participants (Actual) | Interventional | 2020-01-24 | Terminated(stopped due to Due to unforeseen circumstances, the study team was limited in enrolling patients on this trial; thus, it was terminated.) |
| A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)[NCT02527174] | Phase 1 | 0 participants (Actual) | Interventional | 2016-11-30 | Withdrawn(stopped due to Volasertib no longer available) |
| Phase 1 Study of Cladribine Based Induction Therapy (CLAG) With ATRA (All-Trans Retinoic Acid) and Midostaurin in Relapsed/Refractory AML[NCT01161550] | Phase 1 | 11 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Multicenter Randomised Clinical Trial in Acute Myeloid Leukemia Treatment Based on Three Anthracyclines, Comparing Two Types of Consolidation With Different ARA-C Doses Followed by One Year Maintenance[NCT01587430] | Phase 4 | 245 participants (Anticipated) | Interventional | 2010-01-31 | Active, not recruiting |
| Freiburg ZNS-NHL Study: Therapy for Patients With Primary Non-Hodgkin Lymphoma of the CNS - Sequential High Dosage Chemotherapy With Autologous Peripheral Blood Stem Cell Plantation[NCT00647049] | Phase 2 | 78 participants (Anticipated) | Interventional | 2007-01-31 | Recruiting |
| Phase I Study of the Combination of Midostaurin, Bortezomib, and Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia[NCT01174888] | Phase 1 | 34 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A Phase 3 Open-Label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation[NCT02421939] | Phase 3 | 371 participants (Actual) | Interventional | 2015-10-20 | Active, not recruiting |
| Clinical Study on the Safety and Efficacy of QN-030a in Acute Myeloid Leukemia[NCT05665114] | Phase 1 | 18 participants (Anticipated) | Interventional | 2022-12-24 | Recruiting |
| Randomized Phase II Trial On Primary Chemotherapy With High-Dose Methotrexate And High-Dose Cytarabine With Or Without Thiotepa, And With Or Without Rituximab, Followed By Brain Irradiation Vs. High-Dose Chemotherapy Supported By Autologous Stem Cells Tra[NCT01011920] | Phase 2 | 126 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Phase II Study of Punctual, Cyclic, and Intensive Chemotherapy With Liposomal Cytarabine (Depocyt®) CNS Prophylaxis for Adults With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma[NCT02043587] | Phase 2 | 31 participants (Actual) | Interventional | 2014-01-31 | Terminated(stopped due to Original investigator for the trial has left) |
| Intensive Chemotherapy And Immunotherapy In Patients With Newly Diagnosed Primary CNS Lymphoma[NCT00098774] | Phase 2 | 47 participants (Actual) | Interventional | 2004-10-31 | Completed |
| A Phase III Randomized Trial of Gemtuzumab Ozogamicin (Mylotarg) Combined With Conventional Chemotherapy for De Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults[NCT00372593] | Phase 3 | 1,070 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Treatment of Late Isolated Extramedullary Relapse From Acute Lymphoblastic Leukemia (ALL) (Initial CR1≥ 18 Months)[NCT00096135] | | 168 participants (Actual) | Interventional | 2004-11-30 | Completed |
| HEC73543 Versus Salvage Chemotherapy in Relapsed or Refractory FLT3-ITD Acute Myeloid Leukemia: a Multicenter, Open-label, Randomized Phase 3 Trial[NCT05586074] | Phase 3 | 324 participants (Anticipated) | Interventional | 2023-03-03 | Recruiting |
| A Multicenter, Phase 1, Open-Label Study of the FGFR Inhibitor Pemigatinib (INCB054828) Administered After Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) With Adverse or Intermediate Risk Cytogenetics[NCT04659616] | Phase 1 | 32 participants (Anticipated) | Interventional | 2021-01-14 | Recruiting |
| A Randomized Controlled Clinical Trial Comparing Chidamide,Carmustine,Etoposide,Cytarabine and Melphalan With BEAM Regimen Combined With Autologus Hematopoietic Stem Cell Transplantation for the Treatment of Newly Diagnosed PTCL[NCT05931263] | Phase 3 | 104 participants (Anticipated) | Interventional | 2023-06-01 | Recruiting |
| Addition of Sorafenib to G-CSF, Cladribine, Cytarabine and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study[NCT02728050] | Phase 1/Phase 2 | 84 participants (Actual) | Interventional | 2016-12-01 | Completed |
| A Phase II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen[NCT00074165] | Phase 2 | 17 participants (Actual) | Interventional | 2003-01-31 | Terminated(stopped due to Lack of accrual) |
| A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnose[NCT00046930] | Phase 3 | 449 participants (Actual) | Interventional | 2002-09-17 | Completed |
| LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis[NCT02205762] | Phase 2/Phase 3 | 1,400 participants (Anticipated) | Interventional | 2016-11-02 | Recruiting |
| Early Systemic Central Nervous System Prophylaxis in Diffuse Large B-cell Lymphoma[NCT03719560] | Phase 2 | 0 participants (Actual) | Interventional | 2019-07-01 | Withdrawn(stopped due to lack of funding) |
| Clofarabine in Combination With a Standard Remission Induction Regimen (AraC and Idarubicin) in Patients 18-60 Years Old With Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS) : a Phase I-II [NCT00838240] | Phase 1/Phase 2 | 114 participants (Anticipated) | Interventional | 2008-11-30 | Recruiting |
| A Double- Blind, Placebo Controlled, Randomized, Multicenter, Phase II Study to Assess the Efficacy of BL-8040 Addition to Consolidation Therapy in AML Patients[NCT02502968] | Phase 2 | 194 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| Phase Ib/II Study of Uproleselan Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Uproleselan Plus Cladribine Plus LDAC in Patients With Treated Secondary AML (TS-AML)[NCT04848974] | Phase 1/Phase 2 | 37 participants (Anticipated) | Interventional | 2021-06-11 | Recruiting |
| A Phase I/II Study of CPI-613 in Combination With Induction/Consolidation in Older AML Patients[NCT02472626] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2015-12-31 | Withdrawn(stopped due to Drug Supply Issues) |
| A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigator's Choice of Best Available Therapy in Subjects With Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second[NCT04229979] | Phase 3 | 140 participants (Anticipated) | Interventional | 2021-02-08 | Recruiting |
| A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP[NCT02741388] | Phase 1 | 39 participants (Actual) | Interventional | 2016-10-31 | Completed |
| A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations[NCT04293562] | Phase 3 | 1,400 participants (Anticipated) | Interventional | 2020-07-21 | Recruiting |
| A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-Trans Retinoic Acid[NCT02339740] | Phase 3 | 158 participants (Actual) | Interventional | 2015-07-21 | Active, not recruiting |
| Phase II Study of Combination of Hyper-CVAD and Dasatinib (NSC-732517) With or Without Allogeneic Stem Cell Transplant in Patients With Philadelphia (Ph) Chromosome Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL) (A BMT Study)[NCT00792948] | Phase 2 | 97 participants (Actual) | Interventional | 2009-09-01 | Active, not recruiting |
| Multicentered Phase II Study Evaluating the Activity and Toxicity of Liposomal Cytarabine in the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia With Resistent or Relapsed Central Nervous System Involvement[NCT01593488] | Phase 2 | 31 participants (Anticipated) | Interventional | 2012-03-31 | Active, not recruiting |
| A Phase I/II, Open-label Single Institution Study Evaluating Rapamycin in Combination With High-dose Etoposide and Cytarabine in Relapsed or Refractory Aggressive Lymphoid Malignancies[NCT00776373] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2007-01-31 | Terminated |
| CBA Versus FBA Conditioning Followed by Allogeneic HSCT in Treatment of High Risk and Refractory AML[NCT03384212] | Phase 3 | 120 participants (Anticipated) | Interventional | 2016-08-01 | Recruiting |
| A Phase 1 Investigator Sponsored Study of Selinexor in Combination With Daunorubicin and Cytarabine in Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia[NCT02403310] | Phase 1 | 21 participants (Actual) | Interventional | 2015-06-18 | Completed |
| A Phase IIB, Randomized, Double-Blinded, Placebo-Controlled Study of Low Dose Cytarabine and Lintuzumab Compared to Low Dose Cytarabine and Placebo in Patients 60 Years of Age and Older With Previously Untreated AML[NCT00528333] | Phase 2 | 211 participants (Actual) | Interventional | 2007-09-30 | Completed |
| A Safety and Tolerability Trial of Crenolanib and Chemotherapy With Cytarabine and Anthracyclines in Patients With Newly Diagnosed Acute Myeloid Leukemia With FLT3 Activating Mutations[NCT02283177] | Phase 2 | 44 participants (Actual) | Interventional | 2015-01-31 | Completed |
| The Treatment of Down Syndrome Children With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Under the Age of 4 Years[NCT00369317] | Phase 3 | 205 participants (Actual) | Interventional | 2007-03-31 | Completed |
| The Efficacy and Safety of Azacytidine Combined With HAG Regimen Versus Azacytidine for Elderly Patients With Newly Diagnosed Myeloid Malignancy: a Prospective, Randomized Controlled Trial[NCT03873311] | Phase 4 | 114 participants (Anticipated) | Interventional | 2019-09-01 | Recruiting |
| Phase II/III Randomized Study to Improve Overall Survival in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus Mycop[NCT02416388] | Phase 2/Phase 3 | 3,100 participants (Anticipated) | Interventional | 2015-01-31 | Recruiting |
| AML08: A Phase II Randomized Trial of Clofarabine Plus Cytarabine Versus Conventional Induction Therapy And A Phase II Study Of Natural Killer Cell Transplantation In Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT00703820] | Phase 3 | 324 participants (Actual) | Interventional | 2008-08-04 | Completed |
| Non Randomized, Multicenter, Prospective Pediatric Hodgkin Lymphoma Treatment Trial Stratified According to Initial Risk Factors and Response to Chemotherapy, Reduced Cumulative Doses of Antineoplastic Agents and Radiotherapy.[NCT03500133] | Phase 4 | 500 participants (Anticipated) | Interventional | 2017-10-06 | Recruiting |
| A PHASE III, MULTICENTRE, RANDOMIZED, OPEN LABEL CLINICAL TRIAL OF AZACYTIDINE (VIDAZA®) VERSUS FLUDARABINE AND CYTARABINE (FLUGA SCHEME) IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA.[NCT02319135] | Phase 3 | 289 participants (Actual) | Interventional | 2014-10-31 | Completed |
| Dual Growth Factor (rhTPO + G-CSF) and Chemotherapy Combination Regimen for Elderly Patients With Acute Myeloid Leukemia: A Phase II Single-Arm Multicenter Study[NCT05258799] | | 130 participants (Anticipated) | Interventional | 2022-01-21 | Recruiting |
| A Phase 2 Study of Cytokine-induced Memory-like NK Cells in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed AML[NCT04354025] | Phase 2 | 0 participants (Actual) | Interventional | 2023-06-30 | Withdrawn(stopped due to Principal investigator decided not to move forward with the study.) |
| A Phase II Study of Dasatinib (Sprycel®) (NSC #732517) as Primary Therapy Followed by Transplantation for Adults >/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG[NCT01256398] | Phase 2 | 66 participants (Actual) | Interventional | 2010-12-14 | Completed |
| Evaluation of the Safety and Efficacy of Reduced-intensity Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) in Multiple Sclerosis[NCT03113162] | Phase 1 | 15 participants (Anticipated) | Interventional | 2015-05-29 | Recruiting |
| A Phase I-II Trial of DA-EPOCH-R Plus Ixazomib as Frontline Therapy for Patients With MYC-aberrant Lymphoid Malignancies: The DACIPHOR Regimen[NCT02481310] | Phase 1/Phase 2 | 38 participants (Actual) | Interventional | 2015-10-28 | Active, not recruiting |
| A 5 Day Course of Fludarabine and Cytarabine Followed by Full Intensity Allogeneic Stem Cell Transplantation (FA5-Bucy) in Treating Patients With High-risk, Recurrent or Refractory Acute Leukemia and Advanced Myelodysplastic Syndrome[NCT02328950] | | 50 participants (Anticipated) | Observational | 2014-12-31 | Recruiting |
| A Dose Escalation Phase I/II Study of Clofarabine Plus Cytarabine With Growth Factor Priming in Patients Who Are Not Felt to be Candidates for More Aggressive Treatment, With Int-2 and High-Risk MDS[NCT00503880] | Phase 1/Phase 2 | 2 participants (Actual) | Interventional | 2007-05-07 | Terminated(stopped due to Genzyme discontinued Funding) |
| Risk Stratified Treatment for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia: A Phase I/II Non-randomized Study of Trametinib and Azacitidine With or Without Chemotherapy (IND #164058)[NCT05849662] | Phase 1/Phase 2 | 58 participants (Anticipated) | Interventional | 2023-11-30 | Not yet recruiting |
| An Open Label Study to Evaluate the Feasibility of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT02484391] | Phase 2 | 50 participants (Anticipated) | Interventional | 2015-09-30 | Completed |
| Phase II Study of Etoposide, Methylprednisolone, High-dose Cytarabine and Oxaliplatin (ESHAOX) for Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma[NCT00336583] | Phase 2 | 27 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A 2:1 Randomized Phase II Trial to Compare the Efficacy and Safety of Standard Chemotherapy Plus Quizartinib Versus Standard Chemotherapy Plus Placebo in Adult Patients With Newly Diagnosed FLT3 Wild-type AML[NCT04107727] | Phase 2 | 273 participants (Actual) | Interventional | 2019-09-05 | Active, not recruiting |
| A Phase II, Open-label, Single Arm Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Twice Daily Midostaurin (PKC412) Combined With Standard Chemotherapy and as a Single Agent Post-consolidation Therapy in Children With Untreated FLT3-mutate[NCT03591510] | Phase 2 | 23 participants (Anticipated) | Interventional | 2019-03-13 | Recruiting |
| An Investigator Sponsored Phase I Trial of Selinexor (KPT-330) Plus FLAG-Ida for the Treatment of Relapsing/Refractory AML[NCT03661515] | Phase 1 | 16 participants (Actual) | Interventional | 2018-07-17 | Completed |
| A Prospective Randomized Comparison of Idarubicin and High-dose Daunorubicin in Combination With Cytarabine in the Induction Chemotherapy for Acute Myeloid Leukemia[NCT01145846] | Phase 3 | 316 participants (Anticipated) | Interventional | 2010-05-31 | Recruiting |
| Prospective Evaluation of Sorafenib Combined With Standard Therapy in Newly Diagnosed Adult Core-binding Factor Acute Myeloid Leukemia: an Open-label , Randomised Controlled, Multicenter Phase II Trial[NCT05404516] | Phase 2 | 88 participants (Anticipated) | Interventional | 2020-01-01 | Recruiting |
| A Phase I/II Study of CP-4055 in Patients With Platinum Resistant Ovarian Cancer[NCT00831636] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2008-04-30 | Completed |
| "Comparing the Efficacy and Safety of Venetoclax Combined With Decitabine Versus Conventional 7+3 Induction Chemotherapy of Acute Myeloid Leukemia in Young Adults"[NCT05177731] | Phase 3 | 188 participants (Anticipated) | Interventional | 2022-03-01 | Recruiting |
| A Prospective Randomized Comparison of High-dose Cytarabine an High-dose Daunorubicin in the Induction Chemothrapy for Acute Myeloid Leukemia[NCT03507842] | Phase 3 | 380 participants (Actual) | Interventional | 2018-03-01 | Enrolling by invitation |
| A Phase III Multicentric Randomized Study of the Combination of Repeated Doses of Gemtuzumab Ozogamicin (GO) With Daunorubicin and Cytarabine Versus Daunorubicin and Cytarabine in Untreated Patients With Acute Myeloid Leukemia (AML) Aged of 50-70 Years Ol[NCT00927498] | Phase 3 | 280 participants (Actual) | Interventional | 2007-12-31 | Completed |
| Phase II Investigator Sponsored Study of CPX-351 in Combination With Ivosidenib for Patients With IDH1 Mutated Acute Myeloid Leukemia or High-Risk MDS[NCT04493164] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-12-30 | Recruiting |
| A Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia in Adults[NCT02003222] | Phase 3 | 488 participants (Actual) | Interventional | 2014-05-19 | Active, not recruiting |
| A Phase II Study of Rituximab/Bendamustine Followed by Rituximab/Cytarabine for Untreated Mantle Cell Lymphoma[NCT01661881] | Phase 2 | 23 participants (Actual) | Interventional | 2012-08-16 | Active, not recruiting |
| Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived CAR-NK Cells Combined With High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B-Cell Lymphoma[NCT03579927] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2019-10-03 | Withdrawn(stopped due to Lack of Funding) |
| A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia[NCT02723994] | Phase 2 | 171 participants (Actual) | Interventional | 2016-09-30 | Active, not recruiting |
| Phase II Study of Combination of Hyper-CVAD and Dasatinib in Patients With Philadelphia (Ph) Chromosome Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)[NCT00390793] | Phase 2 | 107 participants (Actual) | Interventional | 2006-09-28 | Active, not recruiting |
| Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults[NCT02228772] | Phase 1 | 19 participants (Actual) | Interventional | 2014-12-31 | Completed |
| Outcomes of Patients After Allogenic Hematopoietic Cell Transplantation With Decitabine-containing Conditioning Regimen and Acetylcysteine Treatment[NCT04945096] | Phase 3 | 100 participants (Anticipated) | Interventional | 2021-07-01 | Not yet recruiting |
| A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies[NCT02587598] | Phase 1/Phase 2 | 97 participants (Actual) | Interventional | 2015-12-29 | Terminated |
| A Phase I Study of MEK Inhibitor MEK162 Combined With Idarubicin and Cytarabine Induction in Patients With Relapsed/Refractory RAS-Mutated Acute Myeloid Leukemia[NCT02049801] | Phase 1 | 1 participants (Actual) | Interventional | 2014-12-31 | Terminated(stopped due to logistics) |
| CPX-351 Plus Enasidenib for Relapsed Acute Myelogenous Leukemia Characterized by the IDH2 Mutation[NCT03825796] | Phase 2 | 2 participants (Actual) | Interventional | 2019-04-12 | Active, not recruiting |
| Phase I/II Study of VELCADE®-BEAM and Autologous Hematopoietic Stem Cell Transplantation for Relapsed Indolent Non-Hodgkin's Lymphoma, Transformed or Mantle Cell Lymphoma[NCT00571493] | Phase 1/Phase 2 | 42 participants (Actual) | Interventional | 2006-04-14 | Completed |
| "Magrolimab Plus Intensive Chemotherapy in Newly Diagnosed ELN 2022 Intermediate or Adverse-risk AML or High Risk MDS Patients Intended to Undergo Allogeneic Stem Cell Transplantation, a Phase 2, Single-arm, Open-Label Study"[NCT05829434] | Phase 2 | 108 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017[NCT03643276] | Phase 3 | 5,000 participants (Anticipated) | Interventional | 2018-07-15 | Recruiting |
| Phase I Trial of Ruxolitinib in Combination With a Pediatric Based-regimen for Adolescents and Young Adults (AYAs) With Ph-like Acute Lymphoblastic Leukemia (ALL)[NCT03571321] | Phase 1 | 15 participants (Anticipated) | Interventional | 2019-05-28 | Recruiting |
| An Investigator-Sponsored Randomized Phase II Study of Selinexor in Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients[NCT02835222] | Phase 2 | 100 participants (Anticipated) | Interventional | 2018-02-02 | Recruiting |
| Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™) in Adult Patients With Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)[NCT02013648] | Phase 3 | 203 participants (Anticipated) | Interventional | 2014-07-31 | Active, not recruiting |
| A Randomized Phase 2 Trial of Brentuximab Vedotin (SGN35, NSC# 749710), or Crizotinib (NSC#749005, Commercially Labeled) in Combination With Chemotherapy for Newly Diagnosed Patients With Anaplastic Large Cell Lymphoma (ALCL)[NCT01979536] | Phase 2 | 137 participants (Actual) | Interventional | 2013-11-13 | Active, not recruiting |
| Phase II Study of Combination of Hyper-CVAD and Ponatinib in Patients With Philadelphia (PH) Chromosome Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)[NCT01424982] | Phase 2 | 88 participants (Actual) | Interventional | 2011-10-05 | Active, not recruiting |
| Evaluation of the Efficacy of Induction-consolidation Treatment Using a Double Induction in Patients With AML <60 Years Old, Depending on the Percentage of Blasts in the 14 Day, Residual Disease and Leukemic Hematopoietic Cells[NCT02072811] | Phase 3 | 400 participants (Anticipated) | Interventional | 2014-02-28 | Recruiting |
| Phase Ib Study of Ficlatuzumab With High Dose Cytarabine (HiDAC) in Relapsed and Refractory AML[NCT02109627] | Phase 1 | 17 participants (Actual) | Interventional | 2015-05-01 | Terminated(stopped due to Low Accrual) |
| A Randomized, Open-Label Study of Oral CEP-701 Administered in Sequence With Standard Chemotherapy to Patients With Relapsed Acute Myeloid Leukemia (AML) Expressing FLT-3 Activating Mutations[NCT00079482] | Phase 2 | 224 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Phase 1b/2 Study of Pinometostat in Combination With Standard Induction Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia With MLL Rearrangement[NCT03724084] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2019-01-25 | Terminated(stopped due to Other - Study agent no longer available) |
| Randomized Phase 3 Trial of Decitabine Versus Patient's Choice With Physician's Advice of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT00260832] | Phase 3 | 485 participants (Actual) | Interventional | 2005-11-30 | Completed |
| Phase I Study of Decitabine, Vorinostat, and Cytarabine in Acute Myeloid Leukemia[NCT01130506] | Phase 1 | 17 participants (Actual) | Interventional | 2010-05-17 | Completed |
| Prospective Evaluation of Standard Chemotherapy Regimen of Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT00422591] | Phase 2 | 175 participants (Actual) | Interventional | 2006-12-31 | Completed |
| Dose Finding Safety Run-in Phase Followed by a Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) Administered Prior or After Chemotherapy in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and [NCT02198482] | Phase 2 | 6 participants (Actual) | Interventional | 2016-02-29 | Terminated(stopped due to development program of study drug volasertib was stopped by Boehringer Ingelheim due to manufacturing problems) |
| A Phase 3, Prospective, Randomized Multi-center Intervention Trial of Early Intensification in AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance: A MYNERVA-GIMEMA Study[NCT04174612] | Phase 3 | 172 participants (Anticipated) | Interventional | 2020-04-24 | Recruiting |
| A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG[NCT00039377] | Phase 2 | 58 participants (Actual) | Interventional | 2002-04-30 | Completed |
| High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease[NCT00003631] | Phase 2 | 118 participants (Actual) | Interventional | 1998-08-31 | Completed |
| Randomized Trial of Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (AML)[NCT03836209] | Phase 2 | 181 participants (Actual) | Interventional | 2019-12-06 | Active, not recruiting |
| Phase 1b/2 Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia[NCT02303821] | Phase 1 | 130 participants (Anticipated) | Interventional | 2015-02-16 | Recruiting |
| A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)[NCT02112916] | Phase 3 | 847 participants (Actual) | Interventional | 2014-10-04 | Active, not recruiting |
| "A Novel Pediatric-Inspired Regimen With Reduced Myelosuppressive Drugs for Adults (Aged 18-60) With Newly Diagnosed Ph Negative Acute Lymphoblastic Leukemia"[NCT01920737] | Phase 2 | 39 participants (Actual) | Interventional | 2013-08-31 | Active, not recruiting |
| A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)[NCT04663347] | Phase 1/Phase 2 | 662 participants (Anticipated) | Interventional | 2020-11-03 | Recruiting |
| Dose-Finding Run-in Phase I Followed by a Phase III, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of Crenolanib in Combination With Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Activating FLT3 Mutation[NCT02298166] | Phase 3 | 9 participants (Actual) | Interventional | 2016-11-17 | Terminated(stopped due to The manufacturer Arog Pharmaceuticals Inc has terminated the Agreement Concerning the Support of an Investigator Initiated Trial this became valid on 2020/03/09) |
| Safety, Tolerability and Efficacy of MB07133 Plus Sintilimab in Patients With Hepatocellular Carcinoma，a Phase 1/2a Study[NCT06141109] | Phase 1/Phase 2 | 39 participants (Anticipated) | Interventional | 2022-01-18 | Recruiting |
| International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones[NCT03007147] | Phase 3 | 475 participants (Anticipated) | Interventional | 2017-08-08 | Recruiting |
| A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)[NCT02981628] | Phase 2 | 80 participants (Anticipated) | Interventional | 2017-06-19 | Active, not recruiting |
| Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, Rituximab (TEDDI-R) in Primary CNS Lymphoma[NCT02203526] | Phase 1 | 93 participants (Anticipated) | Interventional | 2014-08-14 | Recruiting |
| Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)[NCT02101853] | Phase 3 | 669 participants (Actual) | Interventional | 2014-12-17 | Active, not recruiting |
| Intensified Methotrexate, Nelarabine (Compound 506U78) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-cell Acute Lymphoblastic Leukemia (ALL) or T-cell Lymphoblastic Lymphoma[NCT00408005] | Phase 3 | 1,895 participants (Actual) | Interventional | 2007-01-22 | Active, not recruiting |
| an Single Center，Single Arm, Phase 3 Study to Evaluate Efficacy and Safety of PD-1 Inhibitor Combined With Azacytidine and HAG Regimen for Patients With Relapsed or Refractory Acute Myeloid Leukemia.[NCT04722952] | Phase 3 | 30 participants (Anticipated) | Interventional | 2021-05-01 | Recruiting |
| High Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)[NCT00075725] | Phase 3 | 3,154 participants (Actual) | Interventional | 2003-12-29 | Completed |
| Venetoclax, Cladribine Plus Low-dose Cytarabine for Relapsed/Refractory Philadelphia Chromosome-negative (Ph-) B-cell Acute Lymphoblastic Leukemia (B-ALL): a Single-arm, Multicenter Study[NCT05657652] | | 36 participants (Anticipated) | Interventional | 2022-10-01 | Recruiting |
| A Phase III Groupwide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease[NCT00025259] | Phase 3 | 1,734 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Phase II Trial Of Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy After Cytoreduction With ESHAP Chemotherapy In Patients With Relapsed Follicular Non-Hodgkin's Lymphoma[NCT00732498] | Phase 2 | 28 participants (Actual) | Interventional | 2006-05-15 | Completed |
| Phase II Study of the Sequential Combination of Low-Intensity Chemotherapy and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)[NCT03147612] | Phase 2 | 21 participants (Actual) | Interventional | 2018-02-08 | Active, not recruiting |
| Clinical Study on the Safety and Efficacy of QN-023a Targeting CD33 in Acute Myeloid Leukemia[NCT05665075] | Phase 1 | 19 participants (Anticipated) | Interventional | 2022-12-24 | Recruiting |
| A Phase I Study of Bortezomib in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML)[NCT01127009] | Phase 1 | 3 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Intensive Treatment For T-CELL Acute Lymphoblastic Leukemia and Advanced Stage Lymphoblastic Non-Hodgkin's Lymphoma: A Pediatric Oncology Group Phase III Study[NCT01230983] | Phase 3 | 573 participants (Actual) | Interventional | 1996-06-30 | Completed |
| iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes[NCT03446638] | | 0 participants (Actual) | Interventional | 2019-05-31 | Withdrawn(stopped due to administratively withdrawn) |
| Clinical Study of Mitoxantrone Hydrochloride Liposome, Carmostine, Etoposide and Cytarabine as Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Patients With Lymphoma[NCT05681403] | | 53 participants (Anticipated) | Interventional | 2023-01-15 | Not yet recruiting |
| Autologous Hematopoietic Cell Transplantation for Core-binding Factor Positive Acute Myeloid Leukemia in the First Complete Remission[NCT01146977] | Phase 2 | 43 participants (Anticipated) | Interventional | 2010-01-31 | Recruiting |
| A Phase II Trial on Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients Progressing or Relapsed After Prior R-CHOP Treatment Not Suitable for Autologous Stem Cell Transplant[NCT01481272] | Phase 2 | 77 participants (Actual) | Interventional | 2011-11-30 | Completed |
| Immune Reconstitution and Biomarker Identification in Patients With Newly Diagnosed Low and Intermediate Risk Hodgkins Lymphoma Receiving Chemotherapy With or Without Radiation Therapy: TXCH-HD-12A[NCT01858922] | Phase 2 | 40 participants (Actual) | Interventional | 2012-12-19 | Active, not recruiting |
| A Phase I/II Study of the Selective Inhibitor of Nuclear Export Selinexor (KPT-330) in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Leukemia or Myelodysplastic Syndrome[NCT03071276] | Phase 2 | 37 participants (Actual) | Interventional | 2016-01-14 | Terminated(stopped due to Due to slow enrollment) |
| Young Adult Acute Lymphoid Leukemia (ALL): Intensification of Pediatric AIEOP LLA-2000 Treatment[NCT01156883] | | 76 participants (Actual) | Interventional | 2010-04-30 | Completed |
| A Randomized Study of Haploidentical Lymphocytes With Nivolumab and Intermediate Dose Cytarabine Versus Nivolumab and Intermediate Dose Cytarabine as Consolidation Treatment in Older Adults With Acute Myeloid Leukemia.[NCT03381118] | Phase 2 | 16 participants (Actual) | Interventional | 2017-06-30 | Terminated(stopped due to Unexpected toxicity) |
| Busulfan, Etoposide, Cytarabine, and Melphalan (BuEAM) as a Conditioning for Autologous Stem Cell Transplantation in Patients With B Cell Lymphoma Except for Diffuse Large B Cell Lymphoma[NCT01178645] | Phase 2 | 42 participants (Anticipated) | Interventional | 2010-07-31 | Recruiting |
| Clinical Efficacy and Safety of DLAAG Protocol in the Treatment of Refractory/Relapse of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome With Blast Excess: a Multicenter, Single-arm, Prospective Clinical Study[NCT03356080] | Phase 2 | 50 participants (Anticipated) | Interventional | 2017-07-07 | Recruiting |
| A PHASE 1 DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVENOUS PF-06747143, ADMINISTERED AS SINGLE AGENT OR IN COMBINATION WITH STANDARD CHEMOTHERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA[NCT02954653] | Phase 1 | 8 participants (Actual) | Interventional | 2016-11-28 | Terminated(stopped due to The study was terminated due to a change in sponsor prioritization.) |
| Efficacy and Safety of Venetoclax Combined With BEAM (Carmustine, Etoposide Cytarabine and Melphalan) Pretreatment in Autologous Stem Cell Transplantation for Diffuse Large B-cell Lymphoma: a Single-center, Randomized Clinical Study[NCT05863845] | | 52 participants (Anticipated) | Interventional | 2023-06-01 | Not yet recruiting |
| An International Phase II Trial Assessing Tolerability and Efficacy of Sequential Methotrexate-Aracytin-based Combination and R-ICE Combination, Followed by HD Chemotherapy Supported by ASCT, in Patients With Systemic B-cell Lymphoma With CNS Involvement [NCT02329080] | Phase 2 | 76 participants (Actual) | Interventional | 2014-12-31 | Active, not recruiting |
| A Phase II, Multicenter, Prospective, Non-randomised, Open-label, Clinical Trial to Evaluate Effectiveness and Safety of BeEAC Conditioning Regimen in Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation[NCT03315520] | Phase 2 | 100 participants (Anticipated) | Interventional | 2016-01-22 | Recruiting |
| A Phase I/II Multi-center Study of HDM201 Added to Chemotherapy in Adult Subjects With Relapsed/Refractory (R/R) or Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT03760445] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2019-11-15 | Withdrawn(stopped due to It was determined that the study design may not be optimal given the changing AML treatment landscape.) |
| Effectiveness of Microcurrents Therapy in Pressure Ulcers in Elderly People: Controlled and Randomized Triple Blind Clinical Trial[NCT03753581] | | 30 participants (Actual) | Interventional | 2018-10-31 | Completed |
| An Open-label Two Strata Study of Bisantrene in Combination With Cytarabine Arabinoside or Bisantrene in Combination With Oral Decitabine/Cedazuridine for the Treatment of Acute Myeloid Leukemia Patients With Extramedullary Disease[NCT05456269] | Phase 1 | 0 participants (Actual) | Interventional | 2022-07-29 | Withdrawn(stopped due to commercial reason) |
| An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Intravenous BI 6727 as Monotherapy or in Combination With Subcutaneous Cytarabine in Patients With Acute Myeloid Leukaemia[NCT00804856] | Phase 2 | 180 participants (Actual) | Interventional | 2008-11-27 | Completed |
| A Phase 1 Trial of the Wee1 Kinase Inhibitor AZD1775 in Combination With Flag Chemotherapy in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia[NCT02791919] | Phase 1 | 0 participants (Actual) | Interventional | 2017-05-25 | Withdrawn(stopped due to Other - Protocol moved to Disapproved) |
| A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia[NCT01822015] | Early Phase 1 | 55 participants (Actual) | Interventional | 2013-03-15 | Completed |
| Phase 1 Study of ADI-PEG 20 Plus Low Dose Cytarabine in Older Patients With Acute Myeloid Leukemia[NCT02875093] | Phase 1 | 23 participants (Actual) | Interventional | 2017-01-20 | Terminated(stopped due to Study Termination) |
| Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Post Approval Registry[NCT01294449] | | 394 participants (Actual) | Observational | 2011-03-31 | Completed |
| A Phase II Study of Twice Daily Cytarabine and Fludarabine in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome[NCT01019317] | Phase 2 | 151 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Phase 3, Randomized, Controlled, Double-Blind, Multinational Clinical Study of the Efficacy and Safety of Vosaroxin and Cytarabine Versus Placebo and Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia (VALOR)[NCT01191801] | Phase 3 | 711 participants (Actual) | Interventional | 2010-12-17 | Completed |
| A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-dose Methotrexate (MTX)-Based Chemo-immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma[NCT00734773] | Early Phase 1 | 0 participants (Actual) | Interventional | 2008-11-30 | Withdrawn(stopped due to Lack of funding) |
| [NCT02662647] | Phase 2 | 30 participants (Actual) | Interventional | 2015-04-30 | Completed |
| An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)[NCT04113616] | Phase 1/Phase 2 | 86 participants (Anticipated) | Interventional | 2019-09-25 | Active, not recruiting |
| Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (R-MACLO/VAM) in Patients With Previously Untreated Mantle Cell Lymphoma[NCT00878254] | Phase 2 | 25 participants (Actual) | Interventional | 2009-03-25 | Active, not recruiting |
| EDOCH Alternating With DHAP Regimen Combined Rituximab or Not to Treat New Diagnosed Younger (Age≤65 Years) Mantle Cell Lymphoma in China: A Multicentre Phase III Trial[NCT02858804] | Phase 4 | 55 participants (Anticipated) | Interventional | 2016-01-31 | Recruiting |
| A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation[NCT00691015] | Phase 2 | 48 participants (Actual) | Interventional | 2008-05-31 | Completed |
| A Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT00583102] | Phase 1/Phase 2 | 23 participants (Actual) | Interventional | 2001-06-30 | Terminated(stopped due to Slow accrual, PI left institution) |
| Rituximab and Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) for Burkitt's and Burkitt's -Like Leukemia/Lymphoma[NCT00669877] | Phase 2 | 56 participants (Actual) | Interventional | 2002-08-31 | Completed |
| Phase 1/2 Study of AMG 531 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Patients With Aggressive Non-Hodgkin's Lymphoma Receiving R-HyperCVAD Alternating With R-Ara-C/MTX[NCT00299182] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Targeted Intensification by a Preparative Regimen for Patients With High-grade B-Cell Lymphoma Utilizing Standard-dose Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Radioimmunotherapy (RIT) Combined With High-dose BEAM Followed by Autologous Stem Cell Transpl[NCT00689169] | Phase 2 | 75 participants (Actual) | Interventional | 2007-08-31 | Completed |
| Phase II Study of Idarubicin, Cytarabine, and Vorinostat in Patients With High-Risk MDS and AML[NCT00656617] | Phase 2 | 106 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Single Arm,Open Label,Phase I Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia[NCT05659992] | Phase 1 | 30 participants (Anticipated) | Interventional | 2022-01-10 | Recruiting |
| A Phase I Study of Lenalidomide Therapy Prior to Re-induction Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine (MEC) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT01904643] | Phase 1 | 17 participants (Actual) | Interventional | 2014-02-28 | Terminated(stopped due to Accrual factor) |
| Reduced Intensity Conditioning Regimen for Low- and Intermediate-risk Myelodysplastic Syndrome Patients Receiving Haploidentical Hematopoietic Stem Cell Transplantation[NCT03412266] | Phase 2 | 50 participants (Anticipated) | Interventional | 2018-02-01 | Recruiting |
| 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 |
| Effect of Priming With Granulocyte-Macrophage Colony-Stimulating Factor During Chemotherapy and Comparison of Timed Sequential Chemotherapy vs 4 Courses of High Dose Cytarabine as Consolidation in Younger Adults With Newly Diagnosed AML[NCT00880243] | Phase 3 | 473 participants (Actual) | Interventional | 1999-03-31 | Completed |
| A Phase I/II Study of Sorafenib (BAY 43-9006) in Combination With Low Dose ARA-C (CYTARABINE) in Elderly Patients With AML or High-Risk MDS[NCT00516828] | Phase 1/Phase 2 | 21 participants (Actual) | Interventional | 2007-11-27 | Completed |
| A Phase II Randomized Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old o[NCT00290498] | Phase 2 | 67 participants (Actual) | Interventional | 2005-08-01 | Completed |
| A Dose-escalated Phase Ⅰ Trial to Assess the Tolerance and Pharmacokinetics of Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML Patient[NCT04402723] | Phase 1 | 8 participants (Actual) | Interventional | 2018-11-06 | Terminated(stopped due to Corporate policy adjustments) |
| A Phase Ib Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of APG-115 as a Single Agent or in Combination With Azacitidine or Cytarabine in Patients With Relapse/Refractory AML and Relapsed/Progressed High/Very High Risk MDS[NCT04275518] | Phase 1 | 102 participants (Anticipated) | Interventional | 2020-07-06 | Recruiting |
| A Phase IV, Randomized Study to Evaluate the Safety and Efficacy of Idarubicin at Different Dosages Combined With Cytarabine as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia[NCT02277847] | Phase 4 | 400 participants (Anticipated) | Interventional | 2010-03-31 | Enrolling by invitation |
| Phase II Study of Multimodality Therapy in Mantle Cell Lymphoma[NCT00004231] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Completed |
| A Phase I Study of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia[NCT03515200] | Phase 1 | 12 participants (Actual) | Interventional | 2018-04-20 | Terminated(stopped due to Due to departure of PI from St. Jude) |
| Combination of Rituximab and Methotrexate Followed by Rituximab and Cytarabine in Elderly Patients With Primary CNS Lymphoma[NCT03569995] | Phase 2 | 35 participants (Anticipated) | Interventional | 2018-11-30 | Recruiting |
| A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia[NCT03324243] | Phase 2 | 0 participants (Actual) | Interventional | 2018-01-31 | Withdrawn(stopped due to Withdrawn: Study halted prior to enrollment of first participant) |
| A Phase I Study of Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced, Pre-Selected CD34+ Cells[NCT02797470] | Phase 1/Phase 2 | 11 participants (Actual) | Interventional | 2016-06-23 | Active, not recruiting |
| Fludarabine and Cytarabine Versus High-dose Cytarabine in Consolidation Treatment of Core-bing Factor Acute Myeloid Leukemia: A Prospective, Multicenter, Randomized Study[NCT02926586] | Phase 4 | 200 participants (Anticipated) | Interventional | 2017-01-01 | Recruiting |
| Epigenetic Reprogramming in Relapse AML: A Phase 1 Study of Decitabine and Vorinostat Followed by Fludarabine, Cytarabine and G-CSF (FLAG) in Children and Young Adults With Relapsed/Refractory AML[NCT03263936] | Phase 1 | 37 participants (Actual) | Interventional | 2017-07-11 | Completed |
| "A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children With Recurrent or Resistant Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), and Non-Hodgkin's Lymphoma (NHL) IND #70,058"[NCT01187810] | Phase 1 | 3 participants (Actual) | Interventional | 2010-08-31 | Terminated(stopped due to drug supply) |
| AGORA-1 /ALFA 2100 Study : A Phase 2 Study of Gemtuzumab Ozogamicin (GO)-Gilteritinib Combination in Adults With FLT3-ITD Relapse/Refractory (R/R) AML[NCT05199051] | Phase 2 | 50 participants (Anticipated) | Interventional | 2023-06-03 | Recruiting |
| Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia[NCT03913559] | Phase 2 | 32 participants (Anticipated) | Interventional | 2019-05-14 | Recruiting |
| "A Randomized Phase II/III Trial of Novel Therapeutics Versus Azacitidine in Newly Diagnosed Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS), Age 60 or Older LEAP: Less-Intense AML Platform Trial"[NCT03092674] | Phase 2/Phase 3 | 78 participants (Actual) | Interventional | 2018-02-02 | Active, not recruiting |
| A Multi-center Randomized Phase II Study of the Impact of CD34+ Cell Dose on Absolute Lymphocyte Count Following High-Dose Therapy and Autologous Stem Cell Transplantation for Relapsed and Refractory Diffuse Large B-cell Lymphoma (DLBCL)[NCT02570542] | Phase 2 | 59 participants (Actual) | Interventional | 2015-10-31 | Active, not recruiting |
| Evaluation of the Incidence and Prognostic Impact of Molecular and Genetic Abnormalities in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms[NCT02084563] | Phase 2 | 455 participants (Actual) | Interventional | 2012-10-31 | Completed |
| CBA Versus FBA Conditioning Followed by Haploidentical Allogeneic HSCT in Treatment of High Risk and Refractory AML[NCT03384225] | Phase 3 | 120 participants (Anticipated) | Interventional | 2016-08-01 | Recruiting |
| A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old[NCT03257241] | Phase 3 | 582 participants (Anticipated) | Interventional | 2017-07-03 | Recruiting |
| A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia With Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy[NCT00109837] | Phase 2 | 79 participants (Actual) | Interventional | 2005-04-30 | Completed |
| National Treatment Program of Philadelphia Chromosome-negative Adult Acute Lymphoblastic Leukemia With Pegylated Asparaginase Added to a Lineage-Targeted Risk- and Minimal Residual Disease-Oriented Strategy[NCT02067143] | Phase 2 | 204 participants (Actual) | Interventional | 2014-05-20 | Completed |
| A Randomized, Double-blind, Multiple-Dose, Two-Cycle, Parallel-Group, Bioequivalence Pretrial of Daunorubicin Cytarabine Liposome for Injection in Older, Naive AML Patients[NCT04920500] | | 16 participants (Anticipated) | Interventional | 2020-09-04 | Recruiting |
| Safety and Efficacy of an Outpatient Schedule of Rituximab, Cytarabine, Carboplatin, and Dexamethasone in Relapsed/Refractory Non-Hodgkin Lymphoma. Phase I/II Trial.[NCT03892421] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2018-04-05 | Completed |
| Treatment of Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia in[NCT06099366] | Phase 2 | 116 participants (Anticipated) | Interventional | 2024-01-15 | Not yet recruiting |
| Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance[NCT02756962] | Phase 2 | 110 participants (Anticipated) | Interventional | 2016-07-06 | Recruiting |
| Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With AML, HR MDS, or Myeloid Blast Phase of CML[NCT02115295] | Phase 2 | 458 participants (Anticipated) | Interventional | 2014-05-19 | Recruiting |
| A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD[NCT01371981] | Phase 3 | 1,645 participants (Actual) | Interventional | 2011-06-20 | Active, not recruiting |
| Efficacy and Safety of Cladribine in Combination With G-CSF, Low-dose Cytarabine and Aclarubicin in Patients With Refractory/Relapsed Acute Myeloid Leukemia: a Phase 2 Clinical Trial[NCT03181815] | Phase 2 | 48 participants (Anticipated) | Interventional | 2016-01-01 | Recruiting |
| A Phase 1b Study of Menin Inhibitor SNDX-5613 in Combination With Daunorubicin and Cytarabine in Newly Diagnosed Patients With Acute Myeloid Leukemia and NPM1 Mutated/FLT3 Wildtype or MLL/KMT2A Rearranged Disease.[NCT05886049] | Phase 1 | 28 participants (Anticipated) | Interventional | 2023-12-19 | Not yet recruiting |
| Eradicating Measurable Residual Disease in Patients With Acute Myeloid Leukemia (AML) Prior to StEm Cell Transplantation (ERASE): A MyeloMATCH Treatment Trial[NCT05554419] | Phase 2 | 184 participants (Anticipated) | Interventional | 2024-08-16 | Not yet recruiting |
| A Phase 3, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Previously Untreated Patients Wit[NCT04778397] | Phase 3 | 346 participants (Anticipated) | Interventional | 2021-07-01 | Active, not recruiting |
| A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas[NCT02130869] | Phase 1 | 8 participants (Actual) | Interventional | 2014-10-10 | Completed |
| Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL)[NCT00103285] | Phase 3 | 5,377 participants (Actual) | Interventional | 2005-04-11 | Completed |
| Phase II Study of Intensive Chemotherapy and Rituximab in Burkitt Lymphoma[NCT00126191] | Phase 2 | 10 participants (Actual) | Interventional | 2005-07-31 | Terminated(stopped due to closed due to slow accrual) |
| A Collaboration Phase 2 Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia[NCT05955261] | Phase 2 | 70 participants (Anticipated) | Interventional | 2023-07-25 | Recruiting |
| A Phase 1 Study Combining Venetoclax With a Pediatric-Inspired Regimen for Newly Diagnosed Adults With B Cell Ph-Like Acute Lymphoblastic Leukemia[NCT05157971] | Phase 1 | 6 participants (Anticipated) | Interventional | 2022-03-17 | Recruiting |
| Phase I Study of Induction Therapy With Cytarabine, High-Dose Mitoxantrone and Dasatinib for Patients With Philadelphia-Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): ALL-6 Protocol[NCT00940524] | Phase 1 | 7 participants (Actual) | Interventional | 2009-07-31 | Completed |
| A Randomized, Phase II Study of CX-01 Combined With Standard Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia[NCT02873338] | Phase 2 | 75 participants (Actual) | Interventional | 2016-08-31 | Completed |
| Phase I Investigator Sponsored Study to Assess the Tolerability and Efficacy of Selinexor in Combination With High Dose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy for Remission Induction in Acute Myelogenous Leukemia (AML)[NCT02573363] | Phase 1 | 25 participants (Actual) | Interventional | 2015-10-07 | Completed |
| Phase III Open-Label Randomized Study of Amonafide L-Malate in Combination With Cytarabine Compared to Daunorubicin in Combination With Cytarabine in Patients With Secondary Acute Myeloid Leukemia (AML)- The ACCEDE Study[NCT00715637] | Phase 3 | 420 participants (Anticipated) | Interventional | 2007-06-30 | Active, not recruiting |
| A Phase II Study of Reduced Intensity Allogeneic Transplantation for Refractory Hodgkin Lymphoma[NCT00908180] | Phase 2 | 47 participants (Anticipated) | Interventional | 2009-07-31 | Not yet recruiting |
| Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia[NCT06007911] | Phase 1 | 36 participants (Anticipated) | Interventional | 2024-02-29 | Not yet recruiting |
| Phase II Prospective Randomized Control Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Inducti[NCT05766514] | Phase 2 | 98 participants (Anticipated) | Interventional | 2024-03-31 | Not yet recruiting |
| A Phase I Study of Tagraxofusp With or Without Chemotherapy in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies[NCT05476770] | Phase 1 | 54 participants (Anticipated) | Interventional | 2022-11-11 | Recruiting |
| Phase 1/2 Study of Liposomal Annamycin in Combination With Cytarabine for the Treatment of Subjects With Acute Myeloid Leukemia (AML)[NCT05319587] | Phase 1/Phase 2 | 63 participants (Anticipated) | Interventional | 2022-09-29 | Recruiting |
| Randomized Phase III Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics[NCT03897127] | Phase 3 | 882 participants (Anticipated) | Interventional | 2019-09-04 | Recruiting |
| Phase II Study of the Combination of Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome (Ph)-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL)[NCT03263572] | Phase 2 | 90 participants (Anticipated) | Interventional | 2017-11-29 | Recruiting |
| Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Blinatumomab With or Without Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia[NCT02877303] | Phase 2 | 80 participants (Anticipated) | Interventional | 2016-11-01 | Recruiting |
| A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single Agent and in Combination With Azacitidine or Cytarabine in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome With an IDH1 Mutation[NCT02719574] | Phase 1/Phase 2 | 336 participants (Actual) | Interventional | 2016-04-30 | Active, not recruiting |
| Clofarabine in Combination With Cytarabine (Ara-C) and G-CSF Priming Followed by Infusion of Ex Vivo Expanded Cord Blood Progenitors for Patients With AML[NCT01031368] | Phase 1 | 29 participants (Actual) | Interventional | 2009-12-31 | Completed |
| Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia[NCT00549848] | Phase 3 | 600 participants (Actual) | Interventional | 2007-10-29 | Completed |
| An Open-label Randomized Controlled Phase II Study of AS1411 Combined With Cytarabine in the Treatment of Patients With Primary Refractory or Relapsed Acute Myeloid Leukemia[NCT01034410] | Phase 2 | 90 participants (Anticipated) | Interventional | 2010-01-31 | Terminated |
| Aezea (Cenersen) in Combination With Chemotherapy for Treatment of Acute Myelogenous Leukemia Subjects ≥55 Years of Age With No Response to Single Frontline Induction Course in a Randomized Double-Blind Placebo-Controlled Multi-Center Study[NCT00967512] | Phase 2 | 0 participants (Actual) | Interventional | 2012-01-31 | Withdrawn(stopped due to Study Was Terminated due to lack of Funding.) |
| Phase II Study of the Combination of CPX-351 and Glasdegib in Previously Untreated Patients With Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia[NCT04231851] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-02-19 | Recruiting |
| A Feasibility Pilot and Phase II Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)[NCT00098839] | Phase 1/Phase 2 | 134 participants (Actual) | Interventional | 2005-02-28 | Completed |
| Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML[NCT00541866] | Phase 1/Phase 2 | 110 participants (Actual) | Interventional | 2007-10-06 | Completed |
| A Phase II Single Arm Study of the Use of CODOX-M/IVAC With Rituximab (R-CODOX-M/IVAC) in the Treatment of Patients With Diffuse Large B-Cell Lymphoma (International Prognostic Index High or High-Intermediate Risk)[NCT00974792] | Phase 2 | 150 participants (Anticipated) | Interventional | 2006-01-31 | Recruiting |
| Safety and Efficacy of Liposomal Cytarabine in Combination With Radiotherapy (RT) and Lomustine for the Treatment of Leptomeningeal Metastasis From Malignant Melanoma[NCT01563614] | Phase 1 | 1 participants (Actual) | Interventional | 2012-03-31 | Terminated(stopped due to No patients can be recruited for this trial anymore due to other therapeutical approaches that became available.) |
| A PHASE I-II MULTICENTER STUDY OF THE CLORETAZINE-DAUNORUBICIN-ARACYTINE COMBINATION FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA (AML) WITH UNFAVORABLE CYTOGENETICS[NCT00840684] | Phase 1/Phase 2 | 135 participants (Anticipated) | Interventional | 2009-01-31 | Completed |
| A Pilot Study To Determine The Toxicity Of The Addition Of Rituximab To The Induction And Consolidation Phases And The Addition Of Rasburicase To The Reduction Phase In Children With Newly Diagnosed Advanced B-Cell Leukemia/Lymphoma Treated With LMB/FAB T[NCT00057811] | Phase 2 | 97 participants (Actual) | Interventional | 2004-06-30 | Completed |
| A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)[NCT00061945] | Phase 1/Phase 2 | 302 participants (Actual) | Interventional | 2003-06-30 | Completed |
| Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (MACLO/IVAM) in Patients With Previously Untreated Mantle Cell Lymphoma[NCT00450801] | Phase 2 | 22 participants (Actual) | Interventional | 2004-04-30 | Completed |
| A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia[NCT01027923] | Phase 1 | 6 participants (Actual) | Interventional | 2010-05-31 | Terminated(stopped due to Withdrawal of support from sponsor) |
| Randomized Phase III Study for the Treatment of Newly Diagnosed Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma[NCT00004228] | Phase 3 | 393 participants (Actual) | Interventional | 2000-06-30 | Completed |
| S0910, A Phase II Study of Epratuzumab (NSC-716711) in Combination With Cytarabine and Clofarabine for Patients With Relapsed or Refractory Ph- Negative Precursor B-Cell Acute Lymphoblastic Leukemia[NCT00945815] | Phase 2 | 35 participants (Actual) | Interventional | 2010-09-30 | Completed |
| A Pilot Pharmacokinetic, Pharmacodynamic and Feasibility Study of Sorafenib in Combination With Cytarabine and Clofarabine in Patients With Refractory or Relapsed Hematologic Malignancies[NCT00908167] | Phase 1 | 44 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Randomized Phase III Trial Evaluating the Role of Autologous Stem Cell Transplantation in Previously Untreated Patients With Stage B and C Chronic Lymphocytic Leukemia[NCT00931645] | Phase 3 | 241 participants (Actual) | Interventional | 2001-04-30 | Completed |
| A Phase I, Open-label, Multi-centre, Multiple Ascending Dose Study to Assess the Safety and Tolerability of AZD1152 in Combination With Low Dose Cytosine Arabinoside (LDAC) in Patients With Acute Myeloid Leukaemia (AML)[NCT00926731] | Phase 1 | 4 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Phase I/II Study of the Oral MDM2 Inhibitor DS-3032b (Milademetan) in Combination With Low Dose Cytarabine (LDAC) in Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML)[NCT03634228] | Phase 1/Phase 2 | 16 participants (Actual) | Interventional | 2018-12-17 | Terminated(stopped due to This study was terminated early due to lack of adequate response, and did not move to the Phase II portion of the study) |
| Phase III, Randomized, Multicenter Study to Assess the Efficacy and Safety of HuM195 (Recombinant Humanized Anti-CD33 Monoclonal Antibody) in Combination With Standardized Chemotherapy Compared to Standardized Chemotherapy Alone in the Treatment of Patien[NCT00006045] | Phase 3 | 0 participants | Interventional | 2000-03-31 | Active, not recruiting |
| A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation[NCT00049517] | Phase 3 | 657 participants (Actual) | Interventional | 2002-12-19 | Completed |
| Phase I Study of Inotuzumab Ozogamicin With 3 and 4 Drug Augmented Berlin-Frankfurt-Münster (BFM) Re-Induction for Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)[NCT03962465] | Phase 1 | 36 participants (Anticipated) | Interventional | 2022-07-22 | Active, not recruiting |
| A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias (Protocol No. P05247)[NCT00907517] | Phase 1 | 24 participants (Actual) | Interventional | 2009-07-29 | Terminated |
| A Single-Arm, Open-Label Phase 2 Pilot Study of Vyxeos (CPX-351) in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia[NCT03575325] | Phase 2 | 11 participants (Actual) | Interventional | 2018-10-11 | Completed |
| Genomics-Based Target Therapy for Children With Relapsed or Refractory Malignancy[NCT02638428] | Phase 2 | 90 participants (Anticipated) | Interventional | 2015-12-31 | Recruiting |
| Phase I Study Evaluating the Chemosensitizing Effect of Everolimus Administered With Cytarabine and Daunorubicin in Patients With Acute Myeloid Leukemia in Relapse[NCT00544999] | Phase 1 | 21 participants (Anticipated) | Interventional | 2007-09-30 | Recruiting |
| A Phase I Dose Escalation Study of Ibrutinib With Idarubicin/Cytarabine for Relapsed/Refractory Acute Myeloid Leukemia[NCT02635074] | Phase 1 | 2 participants (Actual) | Interventional | 2016-11-30 | Terminated(stopped due to safety) |
| A Phase II Pilot Trial of Bortezomib (PS-341, Velcade) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)[NCT00873093] | Phase 2 | 148 participants (Actual) | Interventional | 2009-03-31 | Completed |
| A Phase Ib Feasibility Study of Personalized Kinase Inhibitor Therapy Combined With Induction in Acute Leukemias Who Exhibit In Vitro Kinase Inhibitor Sensitivity[NCT02779283] | Phase 1 | 7 participants (Actual) | Interventional | 2016-01-13 | Completed |
| A Prospective Phase II Trial of Modified MRC UKALL Ⅻ/ECOG E2993 Regimen in the Treatment of Low Risk Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia for Young Adults[NCT02660762] | Phase 2 | 100 participants (Anticipated) | Interventional | 2016-01-31 | Recruiting |
| A Phase II/III Study of Immunomodulation After High Dose Myeloablative Therapy With Autologous Stem Cell Rescue for Refractory/Relapsed Hodgkin Disease[NCT00070187] | Phase 2/Phase 3 | 24 participants (Actual) | Interventional | 2003-11-30 | Completed |
| Phase 2 Study of Cytarabine in Association With Bendamustine and Rituximab in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma[NCT02758925] | Phase 2 | 78 participants (Anticipated) | Interventional | 2016-06-30 | Not yet recruiting |
| An Open-Label Phase 2 Trial of LY2181308 Sodium Administered in Combination With Idarubicin and Cytarabine to Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT00620321] | Phase 2 | 24 participants (Actual) | Interventional | 2008-03-31 | Completed |
| A Pilot Study of Dose Intensification of Methotrexate in Patients With Advanced-Stage (III/IV) Small Non-Cleaved Cell Non-Hodgkins Lymphoma and B-Cell All[NCT00005977] | Phase 3 | 83 participants (Actual) | Interventional | 2000-09-30 | Completed |
| DFCI ALL Adult Consortium Protocol: Adult ALL Trial[NCT01005758] | Phase 2 | 180 participants (Anticipated) | Interventional | 2009-01-31 | Not yet recruiting |
| Eradicating Measurable Residual Disease in Patients With Acute Myeloid Leukemia (AML) Prior to StEm Cell Transplantation (ERASE): A MyeloMATCH Treatment Trial[NCT05628623] | Phase 2 | 184 participants (Anticipated) | Interventional | 2023-10-23 | Not yet recruiting |
| Randomization of Cytarabine Monotherapy Versus Standard-of-Care Vinblastine/Prednisone for Frontline Treatment of Langerhans Cell Histiocytosis (TXCH LCH0115)[NCT02670707] | Phase 3 | 124 participants (Anticipated) | Interventional | 2016-03-07 | Recruiting |
| European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors[NCT02813135] | Phase 1/Phase 2 | 460 participants (Anticipated) | Interventional | 2016-08-03 | Recruiting |
| A Phase II Study of Combination Daunorubicin and Cytarabine (Ara-c) and Nilotinib (Tasigna) (DATA) in Patients Newly Diagnosed With Acute Myeloid Leukemia and KIT Overexpression[NCT01806571] | Phase 2 | 34 participants (Actual) | Interventional | 2015-03-12 | Completed |
| Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treat[NCT00520130] | Phase 1/Phase 2 | 92 participants (Actual) | Interventional | 2007-10-30 | Completed |
| A Multi-center Prospective Single Arm Clinical Study of Reduced Intensive 3 + 5 Idarubicin and Cytarabine Chemotherapy Plus Venetoclax as First-line Treatment for Adults With Acute Myeloid Leukaemia and High-risk Myelodysplastic Syndrome[NCT06050941] | Phase 2 | 60 participants (Anticipated) | Interventional | 2023-10-20 | Not yet recruiting |
| A Dose Escalation And Phase II Study Of Gemtuzumab Ozogamicin (CMA-676; Mylotarg) With High-Dose Cytarabine For Patients With Refractory Or Relapsed Acute Myeloid Leukemia (AML)[NCT00006265] | Phase 2 | 60 participants (Actual) | Interventional | 2001-03-31 | Completed |
| Clinical Evaluation of ASTX727 in Combination With Venetoclax All-Oral Therapy vs Standard of Care Cytarabine and Anthracycline Induction Chemotherapy for Younger FLT3WT Patients With ELN High- Risk Acute Myeloid Leukemia[NCT04817241] | Phase 1/Phase 2 | 55 participants (Anticipated) | Interventional | 2022-02-10 | Active, not recruiting |
| A Phase 3 Trial Investigating Blinatumomab (NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphom[NCT03914625] | Phase 3 | 6,720 participants (Anticipated) | Interventional | 2019-07-03 | Recruiting |
| A Phase II Study of Modified VR-CAP and Acalabrutinib as First Line Therapy for Transplant-Eligible Patients With Mantle Cell Lymphoma[NCT04626791] | Phase 2 | 45 participants (Anticipated) | Interventional | 2021-08-03 | Recruiting |
| A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML[NCT00512252] | Phase 1/Phase 2 | 52 participants (Actual) | Interventional | 2007-07-31 | Completed |
| A Phase II Trial of Cytarabine and Clofarabine in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)[NCT00337168] | Phase 2 | 36 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Dose Densified Chemoimmunotherapy With Early CNS Prophylaxis in Patients Less Than 65 Years With High Risk (aaIPI≥ 2) Diffuse Large B-Cell Lymphoma[NCT01325194] | Phase 2 | 143 participants (Actual) | Interventional | 2011-03-31 | Completed |
| CD-34 Selection for Ex-vivo T-Cell Depletion of Mobilized Peripheral Blood Stem Cells for Recipients of HLA Haploidentical Related Donor Stem Cell Grafts Receiving Intensive Conditioning[NCT00368355] | Phase 2 | 46 participants (Actual) | Interventional | 2000-04-30 | Completed |
| Phase II Study of Maintenance Therapy With Decitabine (NSC #127716) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years[NCT00416598] | Phase 2 | 546 participants (Actual) | Interventional | 2006-11-15 | Completed |
| A Randomized Double-Blind Phase III Study of Ibrutinib During and Following Autologous Stem Cell Transplantation Versus Placebo in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma of the Activated B-Cell Subtype[NCT02443077] | Phase 3 | 302 participants (Anticipated) | Interventional | 2016-10-12 | Active, not recruiting |
| A Phase I Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Pediatric Patients With Acute Myeloid Leukemia (AML)[NCT04915612] | Phase 1 | 18 participants (Anticipated) | Interventional | 2021-05-21 | Recruiting |
| Phase 2 Clinical Trial for Comprehensive Treatment Program for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Tagraxofusp (SL-401) in Combination With HCVAD/Mini-CVD and VENETOCLAX[NCT04216524] | Phase 2 | 40 participants (Anticipated) | Interventional | 2020-05-29 | Recruiting |
| Phase 1 Dose Escalation Study of CPX-351 for Patients With Int-2 or High Risk IPSS Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia After Failure to Hypomethylating Agents[NCT03896269] | Phase 1 | 38 participants (Anticipated) | Interventional | 2019-05-14 | Recruiting |
| A Pilot Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Gemtuzumab Ozogamicin (GO) in Relapsed Refractory Patients With Acute Myeloid Leukemia (AML) and Post-Hypomethylating Agent (Post-HMA) Failure High-Risk Myelodysplastic S[NCT03672539] | Phase 2 | 50 participants (Anticipated) | Interventional | 2018-11-07 | Recruiting |
| Phase II Study of CPX-351 in Combination With Venetoclax in Patients With Acute Myeloid Leukemia (AML)[NCT03629171] | Phase 2 | 52 participants (Anticipated) | Interventional | 2018-10-29 | Recruiting |
| Risk Adapted Treatment of Newly Diagnosed Childhood Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide (Trisenox® ) During Consolidation[NCT00866918] | Phase 3 | 106 participants (Actual) | Interventional | 2009-03-09 | Completed |
| A Phase I and Dose Expansion Cohort Study of Panobinostat in Combination With Fludarabine and Cytarabine in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome[NCT02676323] | Phase 1 | 19 participants (Actual) | Interventional | 2016-05-03 | Terminated(stopped due to Slow accrual) |
| Phase 1B Study of Venetoclax in Combination With Standard Intensive Chemotherapy With Daunorubicin Plus Cytarabine Followed by High-Dose Cytarabine in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia and Advanced Myelodysplastic Syndrome[NCT05342584] | Phase 1 | 99 participants (Anticipated) | Interventional | 2022-05-25 | Recruiting |
| Zevalin/BEAM/Rituximab vs BEAM/Rituximab With or Without Rituximab Maintenance in Autologous Stem Cell Transplantation for Diffuse Large B-Cell Lymphomas[NCT00591630] | Phase 2 | 30 participants (Actual) | Interventional | 2007-11-14 | Completed |
| A Pilot Study of Combined Immunochemotherapy Followed by Reduced Dose RT for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma[NCT00594815] | | 52 participants (Actual) | Interventional | 2002-08-28 | Completed |
| A Randomized Trial for Patients With High-Grade Myeloid Neoplasms With Measurable Residual Disease (MRD): CPX-351 vs. Immediate Allogeneic Hematopoietic Cell Transplantation[NCT04526288] | Phase 2 | 1 participants (Actual) | Interventional | 2021-08-09 | Terminated(stopped due to Terminated due to low accrual) |
| A Phase 2, Randomized, Open-Label, Multicenter Study of Ficlatuzumab in Combination With High-Dose Cytarabine (HiDAC) and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)[NCT04100330] | Phase 2 | 0 participants (Actual) | Interventional | 2020-01-31 | Withdrawn(stopped due to Urgent shift among clinical sites toward efforts to combat COVID-19 pandemic;impacted feasibility of completing study within shelf-life of current IP supply) |
| Ph 1b Dose Escalation Study of OXi4503 as a Single Agent and in Combination With Cytarabine With Subsequent Phase 2 Cohorts for Subjects With Relapsed/Refractory Acute AML and MDS[NCT02576301] | Phase 1/Phase 2 | 105 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| Phase II Study of Low Intensity Allogeneic Transplantation in Mantle Cell Lymphoma[NCT00720447] | Phase 2 | 25 participants (Anticipated) | Interventional | 2008-11-30 | Not yet recruiting |
| Dose-Intensive Chemotherapy Combined With Monoclonal Antibody Therapy and Targeted Radioimmunotherapy for Untreated Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma[NCT00577629] | Phase 2 | 39 participants (Actual) | Interventional | 2005-06-18 | Completed |
| A Randomized, Multi-center Phase II Trial to Assess the Efficacy of 5-azacytidine Added to Standard Primary Therapy in Elderly Patients With Newly Diagnosed AML[NCT00915252] | Phase 2 | 214 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Phase II Trial of Gleevec and Low-Dose Ara-C for Elderly Patients With C-Kit Positive Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes[NCT00451997] | Phase 2 | 10 participants (Actual) | Interventional | 2004-03-31 | Completed |
| High Dose Cytarabine And Mitoxantrone Therapy For Relapsed And Refractory Acute Myeloid And Lymphocytic Leukemia: Effects Of GM-CSF Versus G-CSF On Dendritic Cells And Leukemia Associated Antigen-Specific T-Lymphocytes[NCT00053131] | Phase 2 | 0 participants | Interventional | 1999-01-31 | Completed |
| Randomized Comparison of Consolidation Treatment in Elderly Patients With Acute Myeloid Leukemia: Idarubicin (IDA) Combined With Intermediate-dose Cytarabine Versus Intermediate-dose Cytarabine Alone[NCT04216771] | Phase 2/Phase 3 | 320 participants (Anticipated) | Interventional | 2020-01-31 | Recruiting |
| A Randomized Trial of the I-BFM-SG for the Management of Childhood Non-B Acute Lymphoblastic Leukemia[NCT00764907] | Phase 3 | 4,000 participants (Anticipated) | Interventional | 2002-11-30 | Recruiting |
| Randomized Multicenter Treatment Optimization Study In Chronic Myeloid Leukemia (CML) Interferon-a Vs. Allogeneic Stem Cell Transplantation Vs. High-Dose Chemotherapy Followed By Autografting And Interferon-a Maintainance In Early Chronic Phase[NCT00025402] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 1997-07-31 | Active, not recruiting |
| Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia: A Phase I Study (AflacLL1401)[NCT02680951] | Phase 1 | 0 participants (Actual) | Interventional | 2015-12-31 | Withdrawn(stopped due to Withdrawn due to lack of participants.) |
| A Phase II Study of CPX-351 as a Novel Therapeutic Approach for Patients With Myelodysplastic Syndromes (MDS) After Hypomethylating Agent Failure[NCT03957876] | Phase 2 | 25 participants (Anticipated) | Interventional | 2019-07-25 | Recruiting |
| The Efficiency and Safety of N-acetylcysteine for Prevention of Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation[NCT05907486] | Phase 3 | 260 participants (Anticipated) | Interventional | 2023-08-01 | Not yet recruiting |
| Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission[NCT00002514] | Phase 3 | 1,929 participants (Actual) | Interventional | 1993-05-07 | Completed |
| Phase II Study Of Bryostatin 1 (NSC 339555) And High-Dose 1-B-D-Arabinofuranosylcytosine (HiDAC) In Patients With Refractory Leukemia[NCT00017342] | Phase 2 | 0 participants | Interventional | 2001-07-31 | Completed |
| Phase I/II Study of Hyper-CVAD Plus RAD001 (Everolimus) for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)[NCT00968253] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors[NCT00964743] | | 2 participants (Actual) | Interventional | 2009-08-31 | Terminated(stopped due to Low Accrual) |
| A Phase 1b, Open-label Study of LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia[NCT02652871] | Phase 1 | 36 participants (Anticipated) | Interventional | 2016-05-09 | Completed |
| Dose-intense Idarubicin Induction in Young Patients With Acute Myeloid Leukemia[NCT04069208] | Phase 2 | 42 participants (Anticipated) | Interventional | 2019-09-03 | Recruiting |
| PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia[NCT00494897] | Phase 4 | 374 participants (Actual) | Interventional | 1996-06-30 | Completed |
| A Phase II Study of the Impact of Clinicogenetic Risk-Stratified Management on Outcomes of Acute Myeloid Leukemia in Older Patients[NCT03226418] | Phase 2 | 75 participants (Actual) | Interventional | 2017-07-07 | Active, not recruiting |
| The Clinical Application of Tumor Reversion: A Phase I Study of Sertraline (Zoloft) in Combination With Timed-sequential Cytosine Arabinoside (Ara-C) in Adults With Relapsed and Refractory Acute Myeloid Leukemia (AML)[NCT02891278] | Phase 1 | 6 participants (Actual) | Interventional | 2016-08-11 | Completed |
| Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia[NCT01005914] | Phase 2 | 11 participants (Actual) | Interventional | 2009-06-30 | Terminated(stopped due to Increased rate of bacterial infections) |
| Risk-Stratified Therapy for Acute Myeloid Leukemia in Down Syndrome[NCT02521493] | Phase 3 | 312 participants (Anticipated) | Interventional | 2015-12-23 | Active, not recruiting |
| A Randomized Phase III Study of Intensive Consolidation With High Dose Cytosine Arabinoside in Acute Myelogenous Leukemia (AML-8B)[NCT01324063] | Phase 3 | 160 participants (Anticipated) | Interventional | 1986-11-30 | Completed |
| A Phase III Randomized, Double-Blind Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy + Midostaurin (PKC412) (IND #101261) or Placebo in Newly Diagnosed Patients < 60 Years of Age With FLT3 Mutated Acute M[NCT00651261] | Phase 3 | 717 participants (Actual) | Interventional | 2008-04-30 | Active, not recruiting |
| Phase II Clinical Evaluation of Vorinostat Combined With Salvage Reinduction Chemotherapy Including Gemtuzumab Ozogamicin, Idarubicin and Cytarabine and Vorinostat Maintenance in Relapse or Refractory Acute Myeloid Leukemia Patients With 50 Years or Older[NCT01039363] | Phase 2 | 27 participants (Anticipated) | Interventional | | Not yet recruiting |
| A Multicenter and Randomized Prospective Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia[NCT02200978] | Phase 4 | 176 participants (Actual) | Interventional | 2011-09-30 | Completed |
| Phase I/II Study of Sensitization of Non-M3 Acute Myeloid Leukemia (AML) Blasts to All-trans Retinoic Acid (ATRA) by Epigenetic Treatment With Tranylcypromine (TCP), an Inhibitor of the Histone Lysine Demethylase 1 (LSD1)[NCT02717884] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2015-05-31 | Recruiting |
| Treatment of AML in Adults 50 to 70 Years, Study of Two Anthracyclines and the Interest of Maintenance Treatment With Interleukin 26- ALFA 9801[NCT00931138] | Phase 3 | 420 participants | Interventional | 1999-12-31 | Completed |
| A Phase 1 Study Of Palbociclib (IND#141416), A CDK 4/6 Inhibitor, In Combination With Chemotherapy In Children With Relapsed Acute Lymphoblastic Leukemia (ALL) Or Lymphoblastic Lymphoma (LL)[NCT03792256] | Phase 1 | 15 participants (Anticipated) | Interventional | 2019-04-11 | Active, not recruiting |
| A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination With Cytarabine in Pediatric Patients With Refractory/Relapsed Leukemia[NCT00372619] | Phase 1/Phase 2 | 74 participants (Actual) | Interventional | 2007-03-31 | Completed |
| Clofarabine, Idarubicin, and Cytarabine Combination as Induction Therapy for Younger Patients With Acute Myeloid Leukemia (AML)[NCT01025154] | Phase 2 | 63 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A RANDOMIZED (1:1), DOUBLE-BLIND, MULTI-CENTER, PLACEBO CONTROLLED STUDY EVALUATING INTENSIVE CHEMOTHERAPY WITH OR WITHOUT GLASDEGIB (PF-04449913) OR AZACITIDINE (AZA) WITH OR WITHOUT GLASDEGIB IN PATIENTS WITH PREVIOUSLY UNTREATED ACUTE MYELOID LEUKEMIA[NCT03416179] | Phase 3 | 730 participants (Actual) | Interventional | 2018-04-20 | Completed |
| A Phase II Study of Metronomic and Targeted Anti-angiogenesis Therapy for Children With Recurrent/Progressive Medulloblastoma, Ependymoma and ATRT[NCT01356290] | Phase 2 | 100 participants (Anticipated) | Interventional | 2014-04-30 | Recruiting |
| "A Phase I Trial of Volasertib (BI 6727), an Intravenous Polo-Like Kinase Inhibitor, in Combination With 7+3 Induction Chemotherapy for Patients With Acute Myeloid Leukemia"[NCT02905994] | Phase 1 | 0 participants (Actual) | Interventional | 2016-09-30 | Withdrawn(stopped due to Funding Withdrawn) |
| Prospective Multicentre Phase II Study to Evaluate the Combination of Rituximab and DepoCyte® by Intrathecal Injection in the C5R Chemotherapy Protocol in Patients Between the Ages of 18 and 60 Years With Primary Cerebral Non-Hodgkin Lymphoma and Systemic[NCT00553943] | Phase 2 | 60 participants (Actual) | Interventional | 2007-07-31 | Completed |
| The Prospective Study of FTD Program and HD-MTX-Ara-C Program Contrast in the Treatment of PCNSL Lymphoma.[NCT05274139] | Phase 2 | 20 participants (Actual) | Interventional | 2017-03-02 | Completed |
| Impact of Treatment Intensity on Survival, Quality of Life, and Resource Utilization in Medically Less Fit Adults With Acute Myeloid Leukemia and Analogous Myeloid Neoplasms: A Randomized Pilot Study[NCT03012672] | Phase 2 | 50 participants (Actual) | Interventional | 2016-12-30 | Completed |
| Phase I Study of Escalating Doses of Carfilzomib With Hyper-CVAD in Patients With Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma[NCT02293109] | Phase 1 | 10 participants (Actual) | Interventional | 2015-12-17 | Completed |
| A Phase I/II Study of Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia[NCT02575963] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2012-10-31 | Completed |
| Phase II Randomized Study of Rituximab, Methotrexate, Procarbazine, Vincristine, and Cytarabine With and Without Low-Dose Whole-Brain Radiotherapy for Primary Central Nervous System Lymphoma[NCT01399372] | Phase 2 | 91 participants (Actual) | Interventional | 2011-09-30 | Completed |
| Open-Label, Multicenter Phase Ib/IIa Study For the Evaluation of Dasatinib (Sprycel™) Following Induction and Consolida-tion Therapy as Well as in Maintenance Therapy in Patients With Newly Diagnosed Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)[NCT00850382] | Phase 1/Phase 2 | 89 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Phase 3, Open Label, Single Arm, Multi-Center Study to Evaluate the Efficacy and Safety of Decitabine Combined With HAAG Regimen in Elderly Newly Diagnosed Acute Myeloid Leukemia Patients.[NCT04083911] | Phase 3 | 50 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| HLA-Mismatched Allogeneic Cellular Therapy (Microtransplantation) After Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia < 60 Years[NCT02587871] | Phase 2 | 0 participants (Actual) | Interventional | 2018-12-12 | Withdrawn(stopped due to PI decided not to pursue study) |
| Study Characterizing the Impact of Different Therapeutic Strategies on Event Occurrence at 2 Years, 5 Years, 10 Years, and 15 Years, According to Prognostic Groups in Patients With Hodgkin Lymphoma[NCT00920153] | Phase 3 | 442 participants (Actual) | Interventional | 2008-05-31 | Terminated(stopped due to Other new drugs) |
| Acalabrutinib Plus RICE for Patients With Relapsed/Refractory DLBCL Followed by Autologous Hematopoietic Cell Transplantation and Acalabrutinib Maintenance Therapy[NCT03736616] | Phase 2 | 47 participants (Anticipated) | Interventional | 2019-08-16 | Recruiting |
| Loncastuximab Tesirine in Combination With BEAM (Carmustine, Etoposide, Ara-C, Melphalan) Conditioning Regimen Prior to Autologous Stem Cell Transplant (ASCT) and for Maintenance Therapy in Diffuse Large B-Cell Lymphoma (DLBCL)[NCT05228249] | Phase 1 | 0 participants (Actual) | Interventional | 2023-04-30 | Withdrawn(stopped due to PI left institution and funding sponsor closed study. Study did not open to accrual, and no participants were enrolled.) |
| Phase II Study of The Modified Hyper-CVAD Program for Acute Lymphoblastic Leukemia[NCT00671658] | Phase 2 | 220 participants (Actual) | Interventional | 2002-11-30 | Completed |
| A Pilot Study of Intravenous EZN-2285 (SC-PEG E. Coli L-asparaginase) or Intravenous Oncaspar® in the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia (ALL)[NCT00671034] | Phase 3 | 166 participants (Actual) | Interventional | 2008-07-21 | Completed |
| A Phase II Pilot Study of Bortezomib (PS-341, Velcade) Combined With Reinduction Chemotherapy in Children and Young Adults With Recurrent, Refractory or Secondary Acute Myeloid Leukemia[NCT00666588] | Phase 2 | 52 participants (Actual) | Interventional | 2008-04-30 | Completed |
| A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT02835729] | Phase 1 | 54 participants (Actual) | Interventional | 2016-07-31 | Completed |
| A Programme of Treatment Development for Older Patients With Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome[NCT00454480] | Phase 2/Phase 3 | 2,000 participants (Anticipated) | Interventional | 2006-08-31 | Completed |
| A Randomized Study on CNS Prophylaxis With Liposome-Encapsulated Cytarabine in Association With a Lineage-Targeted and MRD-Oriented Postremission Strategy in Adult ALL[NCT00795756] | Phase 2/Phase 3 | 145 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Clofarabine Plus Low-Dose Cytarabine Induction Followed by Consolidation of Clofarabine Plus Low-Dose Cytarabine Alternating With Decitabine in Frontline Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)[NCT00778375] | Phase 2 | 122 participants (Actual) | Interventional | 2008-10-31 | Completed |
| Venetoclax in Combination With Homoharringtonine and Cytarabine in Newly Diagnosed Subjects With Acute Myeloid Leukemia: a Phase 2/3, the Single-arm, Open-label, Monocentric Study[NCT05805098] | Phase 2/Phase 3 | 60 participants (Anticipated) | Interventional | 2023-03-01 | Recruiting |
| A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes Wi[NCT05365035] | Phase 2 | 60 participants (Anticipated) | Interventional | 2022-09-23 | Recruiting |
| Phase III Randomised Study on Liposomal Cytarabine (DepoCyte®) vs. Intrathecal Triple for CNS-Treatment During Maintenance Therapy in High-Risk Acute Lymphoblastic Leukemia Patients in NOPHO ALL 2008 Treatment Protocol[NCT00991744] | Phase 3 | 100 participants (Anticipated) | Interventional | 2009-01-31 | Suspended(stopped due to Sterility problems in DepoCyte production) |
| A Phase III Study, Randomized, to Evaluate the Reduction of Chemotherapy Intensity in Association With Nilotinib (Tasigna®) in Philadelphia Chromosome-positive (Ph+) ALL of Young Adults (18-59 Years Old) (GRAAPH-2014)[NCT02611492] | Phase 3 | 265 participants (Anticipated) | Interventional | 2016-04-30 | Recruiting |
| Safety and Efficacy Study of Busulfan/FLAG Conditioning Regimen in Patients With Relapsed/Refractory Acute Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation[NCT02784561] | Phase 4 | 80 participants (Anticipated) | Interventional | 2016-07-31 | Not yet recruiting |
| Treatment of Elderly Patients (>60 Years) With Acute Myeloblastic Leukemia or Advanced MDS (RAEB-T): An Open Randomized Study to Test the Efficacy of G-CSF-Priming and a Feasibility Trial of Dose-Reduced Allogeneic Transplantation and of Autologous Stem C[NCT00199147] | Phase 4 | 250 participants | Interventional | 2000-01-31 | Recruiting |
| High-Dose Ara-C Followed by Continuous Infusion Interleukin-2 for Acute Myelogenous Leukemia in First Remission[NCT00136448] | Phase 2 | 30 participants | Interventional | 1993-02-28 | Completed |
| A Phase I Study of M3814 in Combination With MEC in Patients With Relapsed or Refractory Acute Myeloid Leukemia[NCT03983824] | Phase 1 | 48 participants (Anticipated) | Interventional | 2020-05-05 | Recruiting |
| An Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Subjects >=1 and <=30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic L[NCT03384654] | Phase 2 | 47 participants (Actual) | Interventional | 2018-05-14 | Completed |
| Prospectively Randomized Phase III Study of an Individualized Sensitivity-Directed Combination Chemotherapy Versus DTIC as First-Line Treatment in Stage IV Metastatic Melanoma[NCT00779714] | Phase 3 | 360 participants (Anticipated) | Interventional | 2008-10-31 | Recruiting |
| Immunochemotherapy With Rituximab-Bendamustine-Cytarabine for Patients With Mantle Cell Lymphoma Not Eligible for Intensive Regimens or Autologous Transplantation.[NCT00992134] | Phase 2 | 41 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Prospective Single Institution Pilot Study Evaluating the Pharmacokinetics of Sirolimus in Combination With MEC (Mitoxantrone + Etoposide + Cytarabine) in Patients With High Risk Leukemias[NCT00780104] | Phase 1 | 16 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Treatment of Acute Myelogenous Leukemia With the Histone Deacetylase Inhibitor Valproic Cid in Combination With All-trans Retinoic Acid (ATRA) and Low Dose Cytarabine[NCT00995332] | Phase 1/Phase 2 | 36 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Phase I/II Study of Plitidepsin (Aplidin®) in Combination With Cytarabine in Patients With Relapsed/Refractory Leukemia[NCT00780143] | Phase 1/Phase 2 | 3 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Poor recruitment) |
| Multicenter Trial for Treatment of Acute Lymphoblastic Leukemia in Adults (05/93)[NCT00199069] | Phase 4 | 720 participants | Interventional | 1993-04-30 | Completed |
| Intensified Tyrosine Kinase Inhibitor Therapy (Dasatinib NSC# 732517) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)[NCT00720109] | Phase 2/Phase 3 | 63 participants (Actual) | Interventional | 2008-07-14 | Completed |
| Phase I Study of Temozolomide and Intrathecal DepoCyt in Patients With Neoplastic Meningitis[NCT00515788] | Phase 1 | 11 participants (Actual) | Interventional | 2006-02-28 | Terminated(stopped due to Study terminated due to slow accrual with no expansion to additional phase.) |
| A Phase II Study of GM-CSF (Sargramostim) and Rituximab Following Autologous Transplantation For Relapsed Follicular Lymphoma[NCT00521014] | Phase 2 | 14 participants (Actual) | Interventional | 2007-10-31 | Completed |
| UARK 2006-15: A Phase III Randomized Study of Tandem Transplants With or Without Bortezomib (Velcade) and Thalidomide (Thalomid) to Evaluate Its Effect on Response Rate and Durability of Response in Multiple Myeloma Patients[NCT00574080] | Phase 3 | 20 participants (Actual) | Interventional | 2006-07-31 | Terminated(stopped due to low accrual) |
| A Randomized Trial for Patients With Acute Myeloid Leukemia or High Risk Myelodysplatic Syndrome Aged 60 or Over[NCT00005823] | Phase 3 | 2,000 participants (Anticipated) | Interventional | 1998-12-31 | Completed |
| Treatment of High Risk Adult Acute Lymphoblastic Leukemia[NCT00853008] | Phase 4 | 100 participants (Anticipated) | Interventional | 2003-01-31 | Completed |
| Primed Peripheral Blood Stem Cell Autologous Transplantation for Lymphoma and Hodgkin's Disease[NCT00005985] | Phase 2 | 213 participants (Actual) | Interventional | 2000-08-31 | Completed |
| Autologous Transplantation for Non-Hodgkin's Lymphoma and Hodgkin's Disease Using Retrovirally Marked Peripheral Blood Progenitor Cells Obtained After In Vivo Mobilization Using Hematopoietic Cytokines Plus Chemotherapy[NCT00005998] | Phase 2 | 0 participants (Actual) | Interventional | 2000-01-31 | Withdrawn(stopped due to Withdrawn because study never enrolled patients) |
| Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma[NCT00006747] | Phase 2 | 4 participants (Actual) | Interventional | 2000-11-30 | Completed |
| A Phase III Study of STI571 Versus Interferon-a (IFN-a) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)[NCT00006343] | Phase 3 | 0 participants | Interventional | 2000-06-30 | Completed |
| Autologous Peripheral Blood Stem Cell Mobilization and Transplantation for Myelofibrosis[NCT00006367] | Phase 2 | 0 participants | Interventional | 2000-05-31 | Completed |
| The Clinical Observationg on HAM for Acute Myeloid Leukemia[NCT04024241] | | 250 participants (Anticipated) | Observational | 2017-09-01 | Recruiting |
| Phase II Study of Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed By Consolidation With Cladribine Plus LDAC Alternating With Decitabine in Patients With Untreated Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)[NCT01515527] | Phase 2 | 160 participants (Anticipated) | Interventional | 2012-02-07 | Recruiting |
| Phase I/II Study of Decitabine (DAC) Followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia[NCT01794702] | Phase 1/Phase 2 | 65 participants (Actual) | Interventional | 2013-02-20 | Completed |
| Prospective , Multicentric, Randomized Phase II Study, Evaluating the Role of Cranial Radiotherapy or Intensive Chemotherapy With Hematopoietic Stem Cell Rescue After Conventional Chemotherapy for Primary Central Nervous System in Young Patients (< 60 y)[NCT00863460] | Phase 2 | 140 participants (Actual) | Interventional | 2008-10-03 | Active, not recruiting |
| LSA5 PROTOCOL FOR THE TREATMENT OF ADVANCED PEDIATRIC AND ADOLESCENT NON-HODGKIN'S LYMPHOMA (NHL)[NCT00002691] | Phase 2 | 0 participants | Interventional | 1995-08-31 | Completed |
| Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue Versus Oral Methotrexate and Single Versus Double Delayed Intensification for Children With Standard Risk Acute Lymphoblastic Leukemia[NCT00005945] | Phase 3 | 3,054 participants (Actual) | Interventional | 2000-06-30 | Completed |
| Dose Escalation and Phase II Study of Bortezomib (IND #58443) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years[NCT00742625] | Phase 1/Phase 2 | 95 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Intensification Therapy of Mature B-ALL, Burkitt and Burkitt Like and Other High Grade Non-Hodgkin's Lymphoma in Adults[NCT00797810] | Phase 4 | 25 participants (Anticipated) | Interventional | 2006-12-31 | Recruiting |
| AML2003 - Randomized Comparison Between Standard-Therapy and Intensified Therapy for Adult Acute Myeloid Leukemia Patients <= 60 Years. A Prospective, Randomized, Multi-center Therapy-Optimizing-Study.[NCT00180102] | Phase 4 | 600 participants (Anticipated) | Interventional | 2003-12-31 | Completed |
| A Phase III Study of Daunorubicin and Cytarabine +/- G3139 (Genasense, Oblimersen Sodium, NSC #683428, IND #58842), a BCL2 Antisense Oligodeoxynucleotide, in Previously Untreated Patients With Acute Myeloid Leukemia (AML) > / = 60 Years[NCT00085124] | Phase 3 | 500 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Treatment of Older Adults With Acute Lymphoblastic Leukemia[NCT00973752] | Phase 2 | 30 participants (Actual) | Interventional | 2009-08-31 | Completed |
| A Phase 3, Randomized, Controlled, Multi-Center Study to Evaluate the Efficacy and Safety of Decitabine Combined With HAAG Regimen in Newly Diagnosed Acute Myeloid Leukemia Patients Younger Than 60 Years[NCT04087967] | Phase 3 | 162 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| Open Label, Multicenter, Dose Escalation Phase 1a/b Study of RO5429083, Administered as Intravenous Infusion Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia (AML).[NCT01641250] | Phase 1 | 44 participants (Actual) | Interventional | 2012-08-31 | Completed |
| A Study of Bortezomib With Chemotherapy for Relapsed/Refractory Acute Lymphoblastic Leukemia[NCT00440726] | Phase 1/Phase 2 | 31 participants (Actual) | Interventional | 2006-08-04 | Completed |
| Efficacy and Safety of Cladribine in Combination With G-CSF,Low-dose Cytarabine and Aclarubicin in Newly Diagnosed Unfit Patients With Acute Myeloid Leukemia[NCT04254640] | Phase 2 | 34 participants (Anticipated) | Interventional | 2021-03-01 | Not yet recruiting |
| Bortezomib (Velcade®) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies[NCT00439556] | Phase 2 | 40 participants (Actual) | Interventional | 2007-02-13 | Completed |
| A Phase II Study of the Efficacy of the HCVIDDOXIL Regimen in Patients With Newly Diagnosed Peripheral T Cell Lymphoma[NCT00290433] | Phase 2 | 55 participants (Actual) | Interventional | 2003-09-30 | Completed |
| A Multicenter Phase II Study Incorporating DOXIL® and Rituximab Into the Magrath Regimen for HIV-Negative and HIV-Positive Patients With Newly Diagnosed Burkitt's and Burkitt-like Lymphoma[NCT00392990] | Phase 2 | 25 participants (Actual) | Interventional | 2007-02-06 | Completed |
| Phase II Study of Fludarabine, Cytarabine (ARA-C) and Erwinase IV in Patients With Relapsed or Refractory Hematologic Malignancies[NCT02718755] | Phase 2 | 0 participants (Actual) | Interventional | 2018-05-31 | Withdrawn(stopped due to Problem with drug supply) |
| A Collaborative Trial for the Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia[NCT00136084] | Phase 3 | 238 participants (Actual) | Interventional | 2002-08-31 | Completed |
| Phase Ib Study of Fludarabine, Cytarabine (Ara-C) and Pegylated Erwinase (Pegcrisantaspase) in Patients With Relapsed or Refractory Leukemia[NCT04526795] | Phase 1 | 62 participants (Anticipated) | Interventional | 2021-04-09 | Recruiting |
| A Phase 1/2, Multicenter, Open-Label, Single Arm, Dose Escalation and Expansion Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young Adults With FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) P[NCT04240002] | Phase 1/Phase 2 | 97 participants (Anticipated) | Interventional | 2020-09-04 | Recruiting |
| Phase 1B/II Study of Escalating Doses of Pevonedistat (TAK-924, Formerly MLN4924) Administered in Combination With Standard Induction Chemotherapy (Cytarabine and Idarubicin) in Newly Diagnosed High Risk Acute Myelogenous Leukemia (AML)[NCT03330821] | Phase 1/Phase 2 | 53 participants (Anticipated) | Interventional | 2018-04-18 | Active, not recruiting |
| An Open-Label, Randomized Study of Low-Dose Cytarabine in Combination With Arsenic Trioxide Compared With Low-Dose Cytarabine Alone for the Treatment of Elderly Patients With Acute Myeloid Leukemia[NCT00513305] | Phase 3 | 67 participants (Actual) | Interventional | 2007-10-31 | Terminated(stopped due to Study has been stopped by sponsor decision) |
| Intensive Treatment for Intermediate-Risk Relapse of Childhood B-precursor Acute Lymphoblastic Leukemia (ALL): A Randomized Trial of Vincristine Strategies[NCT00381680] | Phase 3 | 275 participants (Actual) | Interventional | 2007-03-31 | Completed |
| A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)[NCT00333840] | Phase 3 | 1,106 participants (Actual) | Interventional | 2000-06-30 | Completed |
| A Phase IIa Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Adult Patients With Acute Myeloid Leukemia (AML)[NCT01066494] | Phase 2 | 20 participants (Anticipated) | Interventional | 2010-01-31 | Active, not recruiting |
| A Randomized Multicenter Phase III Study to Evaluate the Role of All-trans Retinoic Acid (ATRA) in Combination With Induction Chemotherapy, or Azacitidine and Idarubicin as Salvage Therapy and Idarubicin With Cytarabine or Azacitidine as Maintenance Thera[NCT01067274] | Phase 3 | 0 participants (Actual) | Interventional | 2010-04-30 | Withdrawn(stopped due to Study abandoned) |
| A Phase III Randomized, Double-blind, Controlled Study Comparing Clofarabine and Cytarabine Versus Cytarabine Alone in Adult Patients 55 Years and Older With Acute Myelogenous Leukemia (AML) Who Have Relapsed or Are Refractory After Receiving up to Two Pr[NCT00317642] | Phase 3 | 326 participants (Actual) | Interventional | 2006-08-31 | Completed |
| A Phase Ib Study of Belinostat With RDHAP Chemotherapy (Dexamethasone, Cytarabine, Cisplatinum) in Adults With Relapsed or Refractory Diffuse Large B-cell Lymphoma[NCT02532192] | Phase 1 | 0 participants (Actual) | Interventional | 2015-12-31 | Withdrawn(stopped due to Withdrawal of study support.) |
| A Pilot Study of Lestaurtinib (CEP-701) in Combination With Chemotherapy in Young Patients With Relapsed or Refractory FLT3-mutant Acute Myeloid Leukemia[NCT00469859] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2007-06-30 | Completed |
| A Phase II Study of High-Dose Immunosuppressive Therapy Using Carmustine, Etoposide, Cytarabine, Melphalan, Thymoglobulin and Autologous CD34+ Hematopoietic Stem Cell Transplant for the Treatment of Poor Prognosis Multiple Sclerosis[NCT00288626] | Phase 2 | 25 participants (Actual) | Interventional | 2006-07-31 | Completed |
| An Open, Multi-center, Randomized Trial Comparing Haploidentical HSCTs From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies[NCT04547049] | Phase 3 | 160 participants (Anticipated) | Interventional | 2020-09-01 | Recruiting |
| Pilot Study Evaluating the Use of Ex Vivo Expanded Cord Blood Progenitors as Supportive Care Following Chemotherapy (FLAG) in Patients With AML or Acute Leukemia of Ambiguous Lineage[NCT01701323] | Phase 1 | 7 participants (Actual) | Interventional | 2012-12-10 | Terminated |
| Phase II Trial of Intermediate-Dose Cytarabine to Modulate EWS/FLI for Children and Young Adults With Recurrent or Refractory Ewing Sarcoma[NCT00470275] | Phase 2 | 10 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Phase II Trial Of BEAM/Rituximab/Autologous Hematopoietic Stem Cell Transplantation (AHSCT) For Patients With CD20 Positive Non-Hodgkin's Lymphoma[NCT00080886] | Phase 2 | 68 participants (Actual) | Interventional | 2002-05-08 | Completed |
| German Multicenter Trial for Treatment Optimisation in Acute Lymphoblastic Leukemia in Adults and Adolescents Above 15 Years With Rituximab for Improvement of Prognosis in CD20 Positive Standard Risk ALL (Amend 2)[NCT00199004] | Phase 4 | 60 participants (Anticipated) | Interventional | 2004-04-30 | Completed |
| Phase I/II Study of Bortezomib (VELCADE) Plus Rituximab-HyperCVAD Alternating With Bortezomib Plus Rituximab-High Dose Methotrexate/Cytarabine in Patients With Untreated Aggressive Mantle Cell Lymphoma[NCT00477412] | Phase 1/Phase 2 | 107 participants (Actual) | Interventional | 2007-04-03 | Completed |
| Efficacy of 6x R-CHOP Followed by Myeloablative Radiochemotherapy and Autologous Stem Cell Transplantation vs. 3 x (R-CHOP/R-DHAP) Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation[NCT00209222] | Phase 3 | 360 participants (Anticipated) | Interventional | 2004-07-31 | Recruiting |
| Autologous Blood or Marrow Transplantation for Aggressive Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning[NCT00238368] | Phase 2 | 59 participants (Actual) | Interventional | 2004-02-29 | Completed |
| SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring ASCT for Relapsed DLBCL[NCT02366663] | Phase 3 | 3 participants (Actual) | Interventional | 2015-01-31 | Terminated(stopped due to Withdrawal of sponsor support) |
| A Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma[NCT01840566] | Phase 1 | 17 participants (Actual) | Interventional | 2013-04-30 | Active, not recruiting |
| Moscow-Berlin 2008 Multicenter Randomised Study for Treatment of Acute Lymphoblastic Leukemia in Children and Adolescents[NCT01953770] | | 3,000 participants (Anticipated) | Interventional | 2008-02-29 | Active, not recruiting |
| A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults[NCT04530565] | Phase 3 | 348 participants (Anticipated) | Interventional | 2021-01-25 | Recruiting |
| Randomized Controlled Trial to Test Efficacy of High-Dose Methotrexate Consolidation Therapy for BCR-ABL-Negative Acute Lymphoblastic Leukemia in Adults[NCT00131027] | Phase 3 | 240 participants (Anticipated) | Interventional | 2002-09-30 | Recruiting |
| Pilot Study of Crenolanib Combined With Standard Salvage Chmetherapy in Subjects With Relapsed/Refractory Acute Myeloid Leukemia[NCT02626338] | Phase 1/Phase 2 | 16 participants (Actual) | Interventional | 2016-02-29 | Completed |
| Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study[NCT01987297] | Phase 4 | 738 participants (Anticipated) | Interventional | 2012-06-30 | Active, not recruiting |
| Pilot Study of the Efficacy and Tolerance of the Adjunction of a Fish Oil Emulsion to Daunorubicin and Cytarabine Chemotherapy for the Treatment of Acute MYeloblastic Leukemia of Younger Patients With High-risk Cytogenetics[NCT01999413] | Phase 2 | 30 participants (Actual) | Interventional | 2013-11-30 | Completed |
| A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax Co-Administered With Low Dose Cytarabine Versus Low Dose Cytarabine in Treatment Naïve Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy[NCT03069352] | Phase 3 | 211 participants (Actual) | Interventional | 2017-05-23 | Active, not recruiting |
| Accelerated Dose Schedule of Cytarabine Consolidation Therapy for Patients With Acute Myeloid Leukemia (AML) in Complete Remission[NCT04914676] | Phase 2 | 58 participants (Anticipated) | Interventional | 2022-03-08 | Recruiting |
| Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin &Amp; Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Followed by Decitabine Maintenance vs. Observation in Newly-Dia[NCT02085408] | Phase 3 | 727 participants (Actual) | Interventional | 2011-02-04 | Active, not recruiting |
| A Phase 2 Multicenter Study of High Dose Chemotherapy With Autologous Stem Cell Transplant Followed by Maintenance Therapy With Romidepsin for the Treatment of T Cell Non-Hodgkin Lymphoma[NCT01908777] | Phase 2 | 47 participants (Actual) | Interventional | 2013-07-16 | Active, not recruiting |
| Phase II Study of Rituximab Given in Conjunction With Standard Chemotherapy in Primary Central Nervous System (CNS) Lymphoma[NCT00335140] | Phase 2 | 26 participants (Actual) | Interventional | 2007-08-23 | Terminated(stopped due to slow accrual) |
| A Phase I/II, Open-Label, Multi-Center Study Evaluating the Safety and Efficacy of Ruxolitinib and CPX-351 in Combination for the Treatment of Advanced Phase Myeloproliferative Neoplasms[NCT03878199] | Phase 1/Phase 2 | 47 participants (Anticipated) | Interventional | 2019-02-20 | Recruiting |
| A Multicenter Phase II Study Evaluating BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Prior to Autologous Stem Cell Transplant for First and Second Chemosensitive Relapses in Patients With Follicular Lymphoma[NCT02008006] | Phase 2 | 21 participants (Actual) | Interventional | 2014-07-09 | Terminated(stopped due to Insufficient recruitment and unavailability of the treatment) |
| A Phase II Study of Cladribine, Cytarabine, and Granulocyte-Colony Stimulating Factor With Fractionated Gemtuzumab Ozogamicin (CLAG-GO) for the Treatment of Patients With Persistent, Relapsed or Refractory Acute Myeloid Leukemia[NCT04050280] | Phase 2 | 39 participants (Anticipated) | Interventional | 2019-11-01 | Recruiting |
| "Phase I Study of Yttrium-90 Labeled Anti-CD25 (a-Tac) Monoclonal Antibody Plus BEAM for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma, the a-Tac BEAM Regimen"[NCT01476839] | Phase 1 | 25 participants (Actual) | Interventional | 2012-11-09 | Active, not recruiting |
| A Phase I Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia[NCT00081822] | Phase 1 | 23 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A Randomized Comparison of Fludarabine in Combination With Cytarabine Versus High -Dose Cytarabine in Post-remission Therapy for AML1-ETO Acute Myeloid Leukemia[NCT02024308] | Phase 4 | 62 participants (Anticipated) | Interventional | 2010-11-30 | 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 |
| Protocol for Patients With High Risk (Resistant, Refractory, Relapsed or Adverse Cytogenetic) AML[NCT00005863] | Phase 3 | 0 participants | Interventional | 1998-08-31 | Completed |
| An ALFA 2101 Multicenter Randomized Phase II Study: CPX-351 Versus Intensive Chemotherapy in Patients With de Novo Intermediate or Adverse Risk AML Stratified by Genomics[NCT05260528] | Phase 2 | 210 participants (Anticipated) | Interventional | 2023-05-03 | Recruiting |
| Phase III Randomized Study of Induction Chemotherapy With or Without MDR-Modulation With PSC-833 (NSC # 648265, IND # 41121) Followed by Cytogenetic Risk-Adapted Intensification Therapy Followed by Immunotherapy With rIL-2 (NSC # 373364, IND # 1969) vs. O[NCT00006363] | Phase 3 | 720 participants (Actual) | Interventional | 2000-11-30 | Completed |
| A Phase II Trial of Rituxan and BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Progenitor Transplant for Lymphoma[NCT00007852] | Phase 2 | 44 participants (Actual) | Interventional | 2000-09-01 | Completed |
| A Phase II Multicenter Study Comparing Antiretroviral Therapy Alone to Antiretroviral Therapy Plus Cytosine Arabinoside (Cytarabine; Ara-C) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in Human Immunodeficiency Virus (HIV)-Infecte[NCT00001048] | Phase 2 | 90 participants | Interventional | | Completed |
| Phase 1 Study of CPX-351(Cytarabine:Daunorubicin) Liposome Injection in Patients With Advanced Hematologic Malignancies.[NCT00389428] | Phase 1 | 48 participants (Actual) | Interventional | 2006-09-30 | Completed |
| CINJALL: Treatment for Children With Acute Lymphocytic Leukemia[NCT00176462] | Phase 2 | 60 participants (Actual) | Interventional | 2001-02-28 | Completed |
| Programma di Terapia Per Pazienti Affetti da Linfoma Diffuso a Grandi Cellule B CD20 Positive[NCT00556127] | Phase 2 | 94 participants (Actual) | Interventional | 2002-06-30 | Completed |
| A Phase II, Single Arm Study of Tislelizumab Combined With DNA Demethylation Agent +/- CAG Regimen in the Treatment of Patients With High-risk AML or AML Patients Older Than 60 Years of Age Who Are Unfit for Intensive Chemotherapy[NCT04541277] | Phase 2 | 55 participants (Anticipated) | Interventional | 2020-09-01 | Recruiting |
| Safety and Efficacy of Stem Cell Mobilization Using G-CSF (Filgrastim) Alone Compared to Intermediate-dose Cytosine Arabinoside Plus G-CSF in Multiple Myeloma Patients.[NCT01908621] | Phase 3 | 90 participants (Actual) | Interventional | 2013-03-20 | Completed |
| A Randomized, Open-label, Two-period, Two-way Crossover Bioequivalence Study of Two (Cytarabine: Daunorubicin) Liposome for Injection in Elderly AML Subjects[NCT05801835] | | 36 participants (Anticipated) | Interventional | 2023-08-25 | Recruiting |
| A Phase 1, Multicenter, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered FHD-286, as Monotherapy or Combination Therapy, in Subjects With Advanced Hemato[NCT04891757] | Phase 1 | 144 participants (Anticipated) | Interventional | 2021-06-14 | Recruiting |
| A Phase II Study of CPX-351 in Younger Patients < 60 Years Old With Secondary Acute Myeloid Leukemia[NCT04269213] | Phase 2 | 46 participants (Anticipated) | Interventional | 2021-07-29 | Recruiting |
| A Phase I Clinical Trial Testing the Safety of IL-21-Expanded, Off-the-shelf, Third-party Natural Killer Cells (KDS-1001) for the Induction of Relapsed/Refractory Acute Myeloid Leukemia[NCT04220684] | Phase 1 | 21 participants (Anticipated) | Interventional | 2020-06-01 | Recruiting |
| Dexamethasone Plus Salvage Chemotherapy Versus Salvage Chemotherapy Alone in Patients With First Relapsed or Refractory Acute Myeloid Leukemia: a Randomized, Controlled, Open-label, Multicenter, Phase III Study[NCT03765541] | Phase 3 | 142 participants (Anticipated) | Interventional | 2020-01-13 | Recruiting |
| A Phase II Study of Ibrutinib Plus Rituximab Followed by Venetoclax and Hyper-CVAD Consolidation in Newly Diagnosed Young Patients With Mantle Cell Lymphoma: Window II Protocol[NCT03710772] | Phase 2 | 50 participants (Anticipated) | Interventional | 2019-05-01 | Active, not recruiting |
| A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT03164057] | Phase 2 | 206 participants (Actual) | Interventional | 2017-06-15 | Active, not recruiting |
| Treatment of Patients With Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-Lineage Lymphoblastic Lymphoma (B-LLy)[NCT01190930] | Phase 3 | 9,350 participants (Actual) | Interventional | 2010-08-09 | Active, not recruiting |
| A Phase II Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Acute Myeloid Leukemia[NCT00594555] | Phase 2 | 20 participants (Anticipated) | Interventional | 2007-11-30 | Withdrawn(stopped due to Principal Investigator resigned position with the University of Cincinnati, closing study at this site will reopen study in new position) |
| Open Randomized Prospective Clinical Study of Rituximab Combined With Fotemustine, Pemetrexed, Dexamethasone Versus Rituximab Plus Methotrexate, Cytarabine, and Dexamethasone in the Treatment of Primary Central Nervous System Lymphoma[NCT04083066] | Phase 4 | 20 participants (Anticipated) | Interventional | 2019-09-05 | Recruiting |
| A Phase I/II Study of Ribavirin and Low-dose Cytarabine Arabinoside (Ara-C) in Acute Myeloid Leukemia (AML) M4 and M5 Subtypes, and AML With High eIF4E Expression[NCT01056523] | Phase 1/Phase 2 | 29 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Cardioprotection With Dexrazoxane in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS), Myeloid Blast Phase of Chronic Myeloid Leukemia (CML), Ph+ AML, and Myeloid Blast Phase of Myeloproliferative Neoplasms[NCT03589729] | Phase 2 | 100 participants (Anticipated) | Interventional | 2018-09-19 | Recruiting |
| A Trial of Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults (ATACC AML)[NCT03568994] | Early Phase 1 | 26 participants (Actual) | Interventional | 2018-07-10 | Active, not recruiting |
| A Prospective, Single Arm, Multicenter Clinical Study to Evaluate the Efficacy of Venetoclax Combined With Azacytidine or DA Regimen in Prevention the Relapse of Consecutive MRD Positive AML Patients[NCT05361057] | Phase 2 | 40 participants (Anticipated) | Interventional | 2022-05-01 | Recruiting |
| S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease[NCT00723658] | Phase 2 | 0 participants (Actual) | Interventional | 2008-09-30 | Withdrawn(stopped due to lack of accrual) |
| Safety and Efficacy of Stem Cell Mobilization Using G-CSF (Filgrastim) Alone Compared to Intermediate-dose Cytosine Arabinoside Plus G-CSF in Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma Patients.[NCT02722733] | Phase 3 | 90 participants (Anticipated) | Interventional | 2016-03-31 | Recruiting |
| Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study[NCT00866307] | Phase 1 | 104 participants (Actual) | Interventional | 2009-02-23 | Completed |
| A Phase 2 Multicenter Study of First-line Dasatinib Plus Conventional Chemotherapy in Adults With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[NCT01004497] | Phase 2 | 51 participants (Actual) | Interventional | 2010-03-31 | Completed |
| AIEOP LLA 2000 Multicenter Study for the Diagnosis and Treatment of Childhood Acute Lymphoblastic Leukemia[NCT00613457] | Phase 3 | 2,039 participants (Actual) | Interventional | 2000-09-30 | Completed |
| A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Re[NCT03793478] | Phase 1/Phase 2 | 65 participants (Anticipated) | Interventional | 2018-08-15 | Recruiting |
| An Open Label Study of the Effect of Rituxan, High Dose Methotrexate and High Dose Cytarabine on Response Rate in Patients With Primary Central Nervous System Lymphoma.[NCT00517699] | Phase 2 | 5 participants (Actual) | Interventional | 2007-09-30 | Terminated(stopped due to Study was terminated early due to lack of enrollment.) |
| Phase 3 Open-label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation[NCT03182244] | Phase 3 | 276 participants (Actual) | Interventional | 2018-01-15 | Active, not recruiting |
| A Pilot Study of a Novel Sequential Treatment Utilizing CPX-351 as Salvage Chemotherapy Followed by Allogeneic Stem-Cell Transplantation (SCT) Utilizing a Haplo-cord Graft for Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndrome[NCT03393611] | Phase 1 | 14 participants (Actual) | Interventional | 2012-11-30 | Completed |
| Autologous and Allogeneic Transplantation for T-Cell Lymphoma: Impact of Campath -1H and Soluble CD52[NCT00505921] | Phase 2 | 27 participants (Actual) | Interventional | 2003-03-31 | Terminated(stopped due to Slow Accrual.) |
| A Phase II Evaluation of High Dose Chemotherapy and Autologous Stem Cell Transplantation for Intestinal T-cell Lymphomas[NCT00669812] | Phase 2 | 60 participants (Anticipated) | Interventional | 2008-02-29 | Recruiting |
| A Phase 2 Study of SNDX-5613 in Combination With Chemotherapy for Patients With Relapsed or Refractory KMT2A-Rearranged Infant Leukemia[NCT05761171] | Phase 2 | 78 participants (Anticipated) | Interventional | 2023-11-20 | Recruiting |
| Treatment of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)[NCT00411281] | Phase 3 | 0 participants (Actual) | Interventional | 2006-03-31 | Withdrawn(stopped due to Per Group Chair: This study will not move forward.) |
| A Phase I Study of Venetoclax in Combination With Cytotoxic Chemotherapy, Including Calaspargase Pegol, for Children, Adolescents and Young Adults With High-Risk Hematologic Malignancies[NCT05292664] | Phase 1 | 92 participants (Anticipated) | Interventional | 2023-03-29 | Recruiting |
| International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia - Incorporating an Embedded Dose Finding Study for Gemtuzumab Ozogamicin in Combination With Induction Chemotherapy[NCT02724163] | Phase 3 | 700 participants (Anticipated) | Interventional | 2016-04-30 | Recruiting |
| Modified BFM-95 Regimen for the Treatment of Newly Diagnosed T-lymphoblastic Lymphoma in Adults:a Prospective Phase II Study[NCT02396043] | Phase 2 | 50 participants (Anticipated) | Interventional | 2015-03-31 | Recruiting |
| International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With[NCT05658640] | Phase 1/Phase 2 | 26 participants (Anticipated) | Interventional | 2023-04-01 | Not yet recruiting |
| A Clinico-Pathologic Study of Primary Mediastinal B-Cell Lymphoma (IELSG 26)[NCT00689845] | | 120 participants (Anticipated) | Interventional | 2007-06-30 | Recruiting |
| A Phase I Study Evaluating the Safety, Tolerability and Biological Activity of EZN-3042, a Survivin mRNA Antagonist, Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)[NCT01186328] | Phase 1 | 6 participants (Actual) | Interventional | 2010-08-24 | Terminated(stopped due to Enzon Pharmaceuticals decided to end its development of EZN-3042.) |
| A Phase 1 Clinical Study of DSP-2033 (Alvocidib) in Combination With Cytarabine/Mitoxantrone or Cytarabine/Daunorubicin (7+3) in Patients With Acute Myeloid Leukemia[NCT03563560] | Phase 1 | 10 participants (Actual) | Interventional | 2018-05-15 | Completed |
| D-CTAG in the Treatment of Newly Diagnosed Acute Myeloid Leukemia in Elderly Patients[NCT04168138] | | 20 participants (Anticipated) | Interventional | 2019-11-01 | Recruiting |
| Phase I/II Study of the Combination of Quizartinib (AC220) With 5-Azacytidine or Low-Dose Cytarabine for the Treatment of Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)[NCT01892371] | Phase 1/Phase 2 | 200 participants (Anticipated) | Interventional | 2013-11-12 | Completed |
| Optimal Treatment Strategy Based on Prognostic Groups for Pediatric de Novo Acute Myeloid Leukemia[NCT02848183] | Phase 2 | 350 participants | Interventional | 2016-01-31 | Recruiting |
| Bortezomib* and Vorinostat as Maintenance Therapy After Autologous Transplant for Non-Hodgkin Lymphoma Using R-BEAM or BEAM Conditioning Transplant Regimen[NCT00992446] | Phase 2 | 27 participants (Actual) | Interventional | 2010-09-02 | Completed |
| Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia[NCT00906945] | Phase 1/Phase 2 | 39 participants (Actual) | Interventional | 2011-02-28 | Completed |
| Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia[NCT05660473] | Phase 2 | 100 participants (Anticipated) | Interventional | 2022-10-31 | Recruiting |
| ACUTE MYELOID LEUKAEMIA TRIAL 12[NCT00002658] | Phase 3 | 2,000 participants (Anticipated) | Interventional | 1994-01-31 | Active, not recruiting |
| A Phase 1b/2 Study of PCM-075 (Onvansertib) in Combination With Either Low-Dose Cytarabine or Decitabine in Subjects With Acute Myeloid Leukemia (AML)[NCT03303339] | Phase 1/Phase 2 | 72 participants (Actual) | Interventional | 2017-11-17 | Completed |
| Descriptive Study Evaluating the Presence and Function of Natural Killer Cells in Elderly Patients With Acute Myeloid Leukemia in First Remission.[NCT00540956] | | 40 participants (Anticipated) | Interventional | 2006-11-30 | Completed |
| A Phase 1 Study of AC220 (ASP2689) in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT01390337] | Phase 1 | 19 participants (Actual) | Interventional | 2011-10-31 | Completed |
| A Phase 1 Study of the Deglycosylated Ricin A Chain-containing Combined Anti-CD19 and Anti-CD22 Immunotoxin Combotox in Combination With High-Dose Cytarabine in Adult Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia[NCT01408160] | Phase 1 | 18 participants (Actual) | Interventional | 2013-04-30 | Terminated |
| Randomised Comparison of OSHO Induction vs. the German AML Intergroup Standard, Randomised Comparison of AraC/Mtx vs. Flu/AraC/Mtx in Pts Without CR After One Induction Cycle and Randomized Comparison of One vs. Two Consolidation Therapies.[NCT01414231] | Phase 3 | 850 participants (Anticipated) | Interventional | 2002-04-30 | Recruiting |
| Phase II Trial of Venetoclax in Combination With Azacitidine and CAG as Induction Therapy in Patients With Refractory/Relapse Acute Myeloid Leukemia[NCT05807347] | Phase 2 | 42 participants (Anticipated) | Interventional | 2023-02-01 | Recruiting |
| Phase 2 Study Evaluating the Efficacy of Rituximab Plus Modified VPDL for Newly Diagnosed CD20-Positive Adult Acute Lymphoblastic Leukemia[NCT01429610] | Phase 2 | 78 participants (Actual) | Interventional | 2011-11-30 | Active, not recruiting |
| Pivotal Study for High Dose Therapy and Autologous Stem Cell Transplantation in Early Stages of CLL[NCT00275015] | Phase 2 | 169 participants (Actual) | Interventional | 1998-01-31 | Completed |
| A Pilot Study of Arsenic Trioxide-Based Consolidation Therapy for the Primary Treatment of Acute Promyelocytic Leukemia[NCT00276601] | Phase 2 | 0 participants | Interventional | 2004-10-31 | Completed |
| Ofatumumab (O) in Combination With Chemotherapy: Hyper-Fractionated Cyclophosphamide, Doxorubicin, Vincristine and Dexamethasone (O-HyperCVAD) Alternating With Ofatumumab High-Dose Cytarabine and Methotrexate (O-MA) for Patients With Newly Diagnosed Mantl[NCT01527149] | Phase 2 | 37 participants (Actual) | Interventional | 2011-12-06 | Active, not recruiting |
| The Prospective Non-randomized Phase II Clinical Trial of Vemurafenib in Combination With Cytarabine and 2-chlorodeoxyadenosine in Children With Langerhans-cell Hisitocytosis With BRAF V600E Mutation[NCT03585686] | Phase 2 | 12 participants (Anticipated) | Interventional | 2018-06-26 | Recruiting |
| Phase II Evaluation of Gemtuzumab Ozogamicin in Combination With Cytarabine in Untreated Patients Above the Age of 60 Years With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome[NCT00195000] | Phase 2 | 43 participants (Actual) | Interventional | 2003-05-31 | Completed |
| Gemtuzumab Ozogamicin (CMA-676) Followed or Not by Intensive Chemotherapy as Initial Treatment for Elderly Patients With Acute Myeloid Leukemia: An EORTC-LG Pilot Phase II Study[NCT00006122] | Phase 2 | 106 participants (Actual) | Interventional | 2000-06-30 | Completed |
| A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies[NCT00423826] | | 0 participants | Expanded Access | 2007-01-31 | No longer available |
| Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia[NCT00096148] | Phase 2 | 120 participants (Actual) | Interventional | 2004-10-31 | Terminated(stopped due to Administratively complete.) |
| Multicenter Trial for Treatment Optimization in T-lymphoblastic Lymphoma in Adults and Adolescents Older Than 15 Years (GMALL T-LBL 1/2004) (Amend 1)[NCT00199017] | Phase 4 | 75 participants (Anticipated) | Interventional | 2004-04-30 | Completed |
| Dual Growth Factor (rhTPO + G-CSF) and Chemotherapy Combination Regimen in Acute Myeloid Leukemia: Study Protocol for a Randomized Controlled Trial[NCT05382390] | Phase 3 | 130 participants (Anticipated) | Interventional | 2022-01-21 | Recruiting |
| Idarubicin, Cytarabine and Pravastatin (IAP) for Induction of Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT01831232] | | 24 participants (Actual) | Interventional | 2013-05-31 | Completed |
| High-dose Cytarabine/Mitoxantrone Followed by Autotransplantation for Therapy-Related Myelodysplastic Syndrome/Therapy -Related Acute Myeloid Leukemia[NCT00774046] | Phase 2 | 32 participants (Actual) | Interventional | 2002-12-31 | Completed |
| Clinical Observation on the Efficacy and Safety of CLAE Regimen (Cladribine + Cytarabine + Etoposide) in the Treatment of Relapsed/Refractory T- Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma[NCT04679506] | | 50 participants (Anticipated) | Observational [Patient Registry] | 2020-12-31 | Not yet recruiting |
| A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML[NCT01861002] | Phase 1 | 15 participants (Actual) | Interventional | 2013-05-22 | Completed |
| Gleevec (Imatinib) Plus Multi-Agent Chemotherapy For Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[NCT00618501] | Phase 2 | 50 participants (Anticipated) | Interventional | 2005-10-31 | Completed |
| A Randomized, Multi-center, Open-label Phase III Bridging Study to Compare Efficacy of Liposomal Cytarabine-Daunorubicin for Injection With Cytarabine and Daunorubicin in Treating Older Patients With High-Risk (Secondary) Acute Myeloid Leukemia[NCT06182592] | Phase 3 | 120 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| A Phase I, Single-arm, Open Label, Dose Escalation, Multicenter Study of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)[NCT05712278] | Phase 1 | 12 participants (Anticipated) | Interventional | 2023-06-16 | Recruiting |
| A Randomized Phase III Study of the Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia[NCT00186966] | Phase 3 | 394 participants (Actual) | Interventional | 2002-03-31 | Completed |
| Dose-Finding (Phase 1) Study of Continuous Infusion Cladribine, Cytarabine and Mitoxantrone (CI-CLAM) for Adults With Relapsed/Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms Treated at UW/SCCA[NCT04196010] | Phase 1 | 13 participants (Actual) | Interventional | 2020-05-08 | Terminated(stopped due to Terminated due to unfavorable risk-benefit ratio of investigational regimen.) |
| AIDA2000 - Risk-Adapted Therapy for Patients With Acute Promyelocytic Leukemia(APL)[NCT00180128] | Phase 4 | 80 participants (Anticipated) | Interventional | 2000-01-31 | Recruiting |
| A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy[NCT03701308] | Phase 2/Phase 3 | 670 participants (Anticipated) | Interventional | 2019-03-28 | Suspended(stopped due to End of Initial Phase of Multi-phase protocol) |
| Treatment for Newly Diagnosed Patients With Stage III/IV Non-Hodgkin Lymphoma-Study XIII (A Therapeutic Pilot Study)[NCT00187122] | | 42 participants (Actual) | Interventional | 1993-03-31 | Completed |
| Small Noncleaved Cell (SNCC), Non-Hodgkin Lymphoma (NHL), Large Cell NHL (B-Cell) and B-Cell Acute Lymphoblastic Leukemia (B-ALL) Study II[NCT00187161] | Phase 2 | 68 participants (Actual) | Interventional | 1994-11-30 | Completed |
| Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study[NCT00093483] | Phase 1 | 61 participants (Actual) | Interventional | 2002-04-30 | Completed |
| A Randomised Multicentric Phase III Study for the Treatment of Young Patients With High Risk (IPI 2-3) Diffuse Large B-Cell Lymphoma. Dose Dense Chemotherapy + Rituximab +/- Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous St[NCT00499018] | Phase 3 | 399 participants (Anticipated) | Interventional | 2006-01-31 | Active, not recruiting |
| Phase I Study of a Pharmacologically Derived Hybrid Bolus-Infusion Schedule of Flavopiridol (NSC 649890, IND 46,211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Relapsed and Refractory Acute Leu[NCT00470197] | Phase 1 | 35 participants (Actual) | Interventional | 2007-04-30 | Completed |
| Randomized Phase II/III-Study on All-Trans Retinoic Acid in Combination With Induction and Consolidation Therapy as Well as Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT00151242] | Phase 2/Phase 3 | 920 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Large Cell Lymphoma, Pilot Study III[NCT00187070] | | 8 participants (Actual) | Interventional | 1997-12-31 | Completed |
| Phase I/II Trial to Study the Dose, Tolerability and the Effectiveness of Imatinib in Combination With Daunorubicine and Cytarabine for Patients With Chronic Myelogenous Leukemia in Myeloid Acute Phase[NCT00219765] | Phase 1/Phase 2 | 30 participants | Interventional | 2001-05-31 | Terminated |
| Pilot Study I for Treatment of Cancer in Children With Ataxia-Telangiectasia[NCT00187057] | | 6 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-Intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)[NCT01371630] | Phase 1/Phase 2 | 276 participants (Anticipated) | Interventional | 2011-08-26 | Recruiting |
| Treatment of Acute Lymphoblastic Leukemia in Children[NCT00400946] | Phase 3 | 800 participants (Actual) | Interventional | 2005-04-30 | Completed |
| LAL-AR-N-2005: Study Treatment for Children High Risk Acute Lymphoblastic Leukemia[NCT00526409] | Phase 4 | 40 participants (Anticipated) | Interventional | 2005-06-30 | Completed |
| [NCT02937662] | Phase 2 | 60 participants (Anticipated) | Interventional | 2016-10-31 | Recruiting |
| International Collaborative Treatment Protocol for Infants Under One Year With Acute Lymphoblastic or Biphenotypic Leukemia[NCT00550992] | | 445 participants (Anticipated) | Interventional | 2006-01-31 | Recruiting |
| DLCL002 Protocol for Young Patients With Newly Diagnosed High Risk Aggressive B-cell Lymphoma, a Multicenter Phase II Study[NCT03837873] | Phase 2 | 118 participants (Anticipated) | Interventional | 2019-01-21 | Recruiting |
| Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia[NCT03488225] | Phase 2 | 4 participants (Actual) | Interventional | 2018-03-28 | Terminated(stopped due to the study was closed early due to competing trials) |
| PHASE II TRIAL OF CHEMOTHERAPY PLUS RADIOTHERAPY FOR MANAGEMENT OF PRIMARY CENTRAL NERVOUS SYSTEM NON-HODGKIN'S LYMPHOMA (PCNSL)[NCT00002676] | Phase 2 | 36 participants (Actual) | Interventional | 1995-07-31 | Completed |
| A Phase II Trial of ICE Chemotherapy Followed by High Dose BEAM Chemotherapy With Autologous Peripheral Blood Progenitor Cell Transplantation in Patients >= 60 Years Old With Refractory or Relapsed Intermediate Grade Non-Hodgkin's Lymphoma[NCT00002982] | Phase 2 | 0 participants | Interventional | 1997-01-31 | Completed |
| A Phase I Trial of a Combined Regimen of Chemotherapy and 90Y-Labeled, Humanized LL2 (Anti-CD22) Antibody With Peripheral Stem Cell Rescue for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma[NCT00004086] | Phase 1 | 0 participants | Interventional | 1997-06-30 | Active, not recruiting |
| Phase I Investigation of the Feasibility of Combining 5-azacytidine With Highdose Cytarabine (HiDAC) and Mitoxantrone Chemotherapy in a Sequential Manner for Remission Induction in High-risk Acute Myelogenous Leukemia (AML)[NCT01839240] | Phase 1 | 50 participants (Actual) | Interventional | 2012-06-06 | Completed |
| A Single-center Open-label Phase I Study of ALT-801 for ex Vivo Maturation and in Vivo Retargeting of Haploidentical Natural Killer Cells Delivered Following Fludarabine, Cytarabine, and G-CSF in Patients With Relapsed/Refractory Acute Myeloid Leukemia[NCT01478074] | Phase 1 | 0 participants (Actual) | Interventional | 2011-11-30 | Withdrawn(stopped due to The treatment planned was determined to be of low feasibility as no subject was found eligible and able to enroll after screening over 30 subjects) |
| A Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor (CBF) Acute Myeloid Leukemia (AML)[NCT00428558] | Phase 3 | 200 participants (Actual) | Interventional | 2007-07-31 | Completed |
| ALL-BFM 2000 Multi-Center Study for the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia[NCT00430118] | Phase 3 | 4,559 participants (Actual) | Interventional | 2000-07-31 | Completed |
| Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)[NCT00121303] | Phase 3 | 600 participants (Anticipated) | Interventional | 2005-01-31 | Completed |
| A Phase II Study of Ara-C (Cytarabine) in Men With Androgen Independent Prostate Cancer[NCT00480090] | Phase 2 | 10 participants (Actual) | Interventional | 2007-04-30 | Completed |
| FLAT: Fludarabine, Cytarabine and Topotecan in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT00488709] | Phase 4 | 47 participants (Actual) | Interventional | 2003-05-31 | Completed |
| Randomised Trial on Allogeneic Haematopoietic Stem Cell Transplantation in Patients Under the Age of 60 Years With Acute Myeloid Leukemia of Intermediate Risk in First Complete Remission and a Matched Sibling or Unrelated Donor (ETAL-1)[NCT01246752] | Phase 3 | 143 participants (Actual) | Interventional | 2011-02-10 | Terminated(stopped due to decreased recrucial rate as the likelihood of achieving the envisioned patient number in a realistic time-frame was very low.) |
| Multicenter, Phase 2 Clinical Trial Evaluating the Efficacy and Tolerability of Induction and Consolidation Chemotherapy Comprising Fludarabine, Cytarabine, and Attenuated-dose Idarubicin in Elderly Patients With AML(Acute Myeloid Leukemia)[NCT01247493] | Phase 2 | 108 participants (Actual) | Interventional | 2007-06-30 | Completed |
| FLAG-IDA Chemotherapy Induction Follow by Intensive Chemotherapy Postremission +/- Autologous Hemopoietic Stem Cell Transplantation or Bone Marrow Transplantation in Patients With High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemi[NCT00487448] | Phase 4 | 200 participants (Anticipated) | Interventional | 1998-07-31 | Completed |
| Phase I Trial of Cytarabine and Lenalidomide in Relapsed or Refractory Acute Myeloid Leukemia Patients[NCT01246622] | Phase 1 | 32 participants (Actual) | Interventional | 2011-02-07 | Completed |
| A Phase 1 and Pharmacokinetic Study of Uproleselan (GMI-1271, NSC #801708) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia Myelodysplastic Syndrome or Mixed Phenotype Acute Leukemia That Expresses E-Selectin Ligand [NCT05146739] | Phase 1 | 18 participants (Anticipated) | Interventional | 2023-12-23 | Recruiting |
| A Phase 1 Study of Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated Acute Myeloid Leukemia[NCT05024552] | Phase 1 | 22 participants (Anticipated) | Interventional | 2021-08-23 | Recruiting |
| A Study of Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib, and Rituximab (TEDDI-R) in Aggressive B-cell Lymphomas With Secondary Involvement of the Central Nervous System (CNS)[NCT03964090] | Phase 2 | 65 participants (Anticipated) | Interventional | 2019-06-27 | Recruiting |
| A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine (NSC# 102816) to Chemotherapy in Infants With Acute Lymphoblastic Leukemia (ALL) and KMT2A (MLL) Gene Rearrangement[NCT02828358] | Phase 2 | 78 participants (Actual) | Interventional | 2017-04-01 | Active, not recruiting |
| A Phase 1/2 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT02310321] | Phase 1/Phase 2 | 84 participants (Actual) | Interventional | 2015-02-26 | Active, not recruiting |
| Phase II Study of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients With Newly Diagnosed AML at High Risk for Induction Mortality[NCT02286726] | Phase 2 | 56 participants (Actual) | Interventional | 2015-05-04 | Completed |
| Multicenter Randomized Phase II Study of Methotrexate (MTX) and Temozolomide Versus MTX, Procarbazine, Vincristine and Cytarabine for Primary CNS Lymphoma (PCNSL) in the Elderly[NCT00503594] | Phase 2 | 92 participants (Anticipated) | Interventional | 2007-07-31 | Recruiting |
| Phase I Dose Escalating Trial of VELCADE (PS-341) in Combination With Idarubicin and Cytosine Arabinoside in Patients With Acute Myelogenous Leukemia[NCT00505700] | Phase 1 | 36 participants (Anticipated) | Interventional | 2003-07-31 | Completed |
| LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive[NCT00526305] | Phase 4 | 100 participants (Anticipated) | Interventional | 2000-01-31 | Completed |
| A Pilot Study Of Cytarabine And High-Dose Mitoxantrone For Relapsed Or Refractory Hematologic Malignancies[NCT00047021] | Phase 2 | 3 participants (Actual) | Interventional | 2001-11-30 | Completed |
| Phase III - Study on All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT00151255] | Phase 3 | 500 participants (Anticipated) | Interventional | 2004-06-30 | Completed |
| A Phase I-II Study of Triciribine Phosphate Monohydrate (PTX-200) Plus Cytarabine in Refractory or Relapsed Acute Leukemia[NCT02930109] | Phase 1/Phase 2 | 40 participants (Anticipated) | Interventional | 2016-09-30 | Recruiting |
| LAL-BR/2001: Study Treatment to Low Risk ALL[NCT00526175] | Phase 4 | 150 participants (Anticipated) | Interventional | 2001-06-30 | Completed |
| [NCT00529880] | Phase 2 | 19 participants (Anticipated) | Interventional | 2004-12-31 | Recruiting |
| A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias[NCT04623944] | Phase 1 | 90 participants (Anticipated) | Interventional | 2020-09-21 | Recruiting |
| Modified BFM (Berlin-Frankfurt-Munster)Backbone Therapy for Chinese Children or Adolescents With Newly Diagnosed Lymphoblastic Lymphoma[NCT02845882] | Phase 3 | 150 participants (Anticipated) | Interventional | 2016-01-31 | Active, not recruiting |
| A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807)[NCT00557193] | Phase 3 | 218 participants (Actual) | Interventional | 2008-01-15 | Active, not recruiting |
| A Phase 1B/2A, Open-label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Fosciclopirox Alone and In Combination With Cytarabine in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)[NCT04956042] | Phase 1/Phase 2 | 28 participants (Anticipated) | Interventional | 2021-08-27 | Recruiting |
| A Phase 1 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT02236013] | Phase 1 | 80 participants (Actual) | Interventional | 2015-01-07 | Completed |
| LBL 2018 - International Cooperative Treatment Protocol for Children and Adolescents With Lymphoblastic Lymphoma[NCT04043494] | Phase 3 | 683 participants (Anticipated) | Interventional | 2019-08-23 | Recruiting |
| Ma-Spore ALL 2010 Study[NCT02894645] | Phase 4 | 500 participants (Anticipated) | Interventional | 2008-10-31 | Recruiting |
| A Phase Ib/II Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML [NCT03850535] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2019-03-25 | Terminated(stopped due to Sponsor's decision to terminate the study after Phase 1; will not proceed with Phase 2.) |
| A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion[NCT03570983] | Phase 2 | 100 participants (Anticipated) | Interventional | 2018-09-05 | Recruiting |
| A Phase I/II, Open-label Multicenter Trial to Determine Safety, Pharmacokinetics and Efficacy of GMI-1271 in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia[NCT02306291] | Phase 1/Phase 2 | 91 participants (Actual) | Interventional | 2015-03-31 | Completed |
| A Phase II Study of Cloretazine® (VNP40101M) for Elderly Patients With De Novo Poor Risk Acute Myelogenous Leukemia[NCT00354276] | Phase 2 | 85 participants (Anticipated) | Interventional | 2006-05-31 | Active, not recruiting |
| A PedAL/EuPAL Phase 1/2 Trial of IMGN632 in Pediatric Patients With Relapsed or Refractory Leukemia[NCT05320380] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2023-08-01 | Withdrawn(stopped due to Withdrawn per CS0150757) |
| A Phase 1/1b Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone and in Combination With Cytarabine (Ara-C) in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome With Wild-Type TP53[NCT02909972] | Phase 1 | 55 participants (Actual) | Interventional | 2016-09-30 | Completed |
| Primary Comparison of Liposomal Anthracycline Based Treatment Versus Conventional Care Strategies Before Allogeneic Stem Cell Transplantation in Patients With Higher Risk MDS and Oligoblastic AML[NCT04061239] | Phase 2 | 150 participants (Anticipated) | Interventional | 2019-08-19 | Recruiting |
| Phase I Trial of Brentuximab Vedotin With Re-induction Chemotherapy in Patients With Relapsed, CD30 Expressing, Acute Myeloid Leukemia (AML)[NCT01830777] | Phase 1 | 22 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Phase I Dose Escalation Study With Expansion to Evaluate the Safety of SEPHB4-HSA in Combination With Cytarabine or Liposomal Vincristine in Patients With Relapsed or Refractory Acute Leukemia[NCT03519984] | Phase 1 | 3 participants (Actual) | Interventional | 2018-05-09 | Terminated(stopped due to Study drug supply issue) |
| Treatment of Peripheral T-cell Lymphoma With Aggressive Induction Chemotherapy Followed by Autologous Stem Cell Transplant Using Denileukin Diftitox (Ontak) for In-vivo Purging and Post-Transplant Therapy: A Multicenter Phase II Clinical Trial[NCT00632827] | Phase 2 | 21 participants (Actual) | Interventional | 2008-07-01 | Terminated(stopped due to Manufacturing shortage of both Diftitox and Doxil) |
| A Phase II Study of Intensive Consolidation and Stem Cell Mobilization Therapy With Ofatumumab, Etoposide, and High-dose Ara-C (OVA), Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymp[NCT01555541] | Phase 2 | 19 participants (Actual) | Interventional | 2012-05-25 | Completed |
| A Phase 2 Randomized Study Comparing Venetoclax and Azacitidine to Induction Chemotherapy for Newly Diagnosed Fit Adults With Acute Myeloid Leukemia[NCT04801797] | Phase 2 | 172 participants (Anticipated) | Interventional | 2021-05-20 | Recruiting |
| A Prospective Randomized Phase I/II Study of Clofarabine (Clo) and Ara-C vs Clo and Ida vs Clo Plus Ida and Ara-C in Patients With First Relapse or First Salvage of Primary Refractory AML; and High-Grade MDS(>/= 10% Blasts); or CML in Myeloid Blasts Phase[NCT00067028] | Phase 2 | 116 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults With Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality[NCT01804101] | | 48 participants (Actual) | Interventional | 2013-05-07 | Completed |
| BUSULFAN AND CYCLOPHOSPHAMIDE FOR CYTOREDUCTION OF PATIENTS WITH ACUTE AND CHRONIC LEUKEMIAS AND MYELODYSPLASTIC SYNDROMES UNDERGOING ALLOGENEIC BONE MARROW TRANSPLANTATION WHO CANNOT BE TREATED WITH TOTAL BODY IRRADIATION[NCT00002502] | Phase 2 | 0 participants | Interventional | 1992-07-31 | Completed |
| TREATMENT OF ADULT PATIENTS WITH RELAPSING ACUTE LYMPHOCYTIC LEUKEMIA, A MULTICENTER TRIAL[NCT00002532] | Phase 2 | 0 participants | Interventional | 1993-01-31 | Active, not recruiting |
| A PHASE II STUDY OF MITOXANTRONE AND HIGH-DOSE ARA-C FOLLOWED BY INTENSIVE CONSOLIDATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE FOR MYELOID BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA (CML)[NCT00002598] | Phase 2 | 30 participants (Anticipated) | Interventional | 1994-06-30 | Completed |
| A RANDOMIZED PHASE III TRIAL COMPARING DEXAMETHASONE WITH PREDNISONE IN INDUCTION TREATMENT AND BONE MARROW TRANSPLANTATION WITH INTENSIVE MAINTENANCE TREATMENT IN ADOLESCENT AND ADULT ACUTE LYMPHOBLASTIC LEUKEMIA (ALL-4)[NCT00002700] | Phase 3 | 392 participants (Anticipated) | Interventional | 1995-08-31 | Completed |
| A Phase II Trial of T-Cell Depleted Marrow Grafts Combined With Infusions of G-CSF Stimulated, CD34 Ceprate Stem Cell Column Selected, E-Rosette Depleted Peripheral Blood Progenitor Cells Derived From HLA Haplotype Matched Related Donors for Patients With[NCT00002718] | Phase 2 | 31 participants (Actual) | Interventional | 1995-11-30 | Completed |
| A Phase II Study of Compound 506U78 in Patients With Refractory T-Cell Malignancies-POG/CCG Intergroup Study[NCT00002970] | Phase 2 | 148 participants (Actual) | Interventional | 1997-06-30 | Completed |
| Multicenter Trial for Treatment of Acute Lymphocytic Leukemia in Adults (Pilot Study 06/99)[NCT00199056] | Phase 4 | 225 participants | Interventional | 1999-10-31 | Completed |
| Treatment of Newly Diagnosed Childhood AML Using a Timed-Sequential Remission Induction and Consolidation Followed by Single Dose Melphalan With Peripheral Stem Cell Rescue: A POG Pilot Study[NCT00004056] | Phase 1 | 35 participants (Actual) | Interventional | 1999-10-31 | Completed |
| The Value of High Dose Versus Standard Dose ARA-C During Induction and of IL-2 After Intensive Consolidation/Autologous Stem Cell Transplantation in Patients (Age 15-60 Years) With Acute Myelogenous Leukemia. A Randomized Phase II Trial of the EORTC and t[NCT00004128] | Phase 3 | 2,000 participants (Anticipated) | Interventional | 1999-09-30 | Active, not recruiting |
| A Study to Determine the Safety and Efficacy of Using CD8-High Density Microparticles (CD8-HDM) to Deplete CD8+ Cells From Donor Lymphocyte Infusion in Order to Reduce Graft-versus-Host Disease (GvHD) Without Compromising an Anti-Leukemia Effect in Patien[NCT00004878] | Phase 2 | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to study never opened) |
| Chemotherapy (CT) Followed by Donor Lymphocyte Infusion (DLI) Plus Interleukin 2 (IL-2) for Patients With Relapse Acute Myeloid or Lymphoid Leukemia After Allogeneic Hematopoietic Transplant[NCT00005802] | Phase 1/Phase 2 | 0 participants | Interventional | 1999-06-30 | Completed |
| A Data Collection Study to Compare the Outcome for Children With Advanced Unilateral Retinoblastoma Treated With or Without Post-Enucleation Chemotherapy ± Radiotherapy on RB 2005 11 With Historical Controls Receiving no Additional Therapy[NCT00360750] | | 0 participants | Interventional | 2005-09-30 | Active, not recruiting |
| A Multi-Center, Open-Label, Phase 1/1b Study of Escalating Doses of RO5503781 Administered Orally as 1) a Single Agent, 2) In Combination With Cytarabine, or 3) With Cytarabine and Anthracycline and 4) Assessing PK and Safety of New Optimized Formulation [NCT01773408] | Phase 1 | 122 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Single-Arm Phase I/II Study Evaluating the Safety and Clinical Efficacy Of the 2-nd Generation CD19 Autologous CAR T Cells on the CliniMACS Prodigy Automated Manufacturing Platform in Treatment of Paediatric And Young Adult Patients With Relapsed/Refrac[NCT03467256] | Phase 1/Phase 2 | 18 participants (Anticipated) | Interventional | 2018-05-14 | Active, not recruiting |
| Phase I-II Clinical Trial for the Evaluation of Brentuximab Vedotin Plus Etoposide, Solumoderin (Methylprednisolone), High Dose ARA-C (Cytarabine) and Cisplatin in the Transplant and Post-transplant Management for Relapsed or Refractory Classical Hodgkin [NCT02243436] | Phase 1/Phase 2 | 67 participants (Actual) | Interventional | 2014-11-11 | Completed |
| A Phase 1, Multicenter, Open-Label, Safety Study of AG-120 or AG-221 in Combination With Induction Therapy and Consolidation Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia With an IDH1 and/or IDH2 Mutation[NCT02632708] | Phase 1 | 153 participants (Actual) | Interventional | 2015-12-31 | Active, not recruiting |
| Phase I/II Study of Lenalidomide Maintenance Following BEAM (+/- Rituximab) for Chemo-Resistant or High Risk Non-Hodgkin?s Lymphoma[NCT01035463] | Phase 1/Phase 2 | 74 participants (Actual) | Interventional | 2009-11-12 | Completed |
| Phase-II Study Evaluating Midostaurin in Induction, Consolidation and Maintenance Therapy Also After Allogeneic Blood Stem Cell Transplantation in Patients With Newly Diagnosed Acute Myeloid Leukemia Exhibiting a FLT3 Internal Tandem Duplication[NCT01477606] | Phase 2 | 451 participants (Actual) | Interventional | 2012-05-31 | Completed |
| A Phase II Study Of Induction With Daunorubicin, Cytarabine, And Cyclosporine All By Continuous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) In Patients Of Age 56 Or Older[NCT00066794] | Phase 2 | 69 participants (Actual) | Interventional | 2004-07-31 | Completed |
| A Phase I Study of Triapine in Combination With High Dose Ara-C (Hi-DAC) in Patients With Advanced Hematologic Malignancies[NCT00077181] | Phase 1 | 48 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies[NCT00070538] | Phase 1 | 0 participants | Interventional | 2003-06-30 | Completed |
| A Phase I Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Refractory or Relapsed Leukemias[NCT00258271] | Phase 1 | 18 participants (Anticipated) | Interventional | 2005-03-31 | Completed |
| A Phase II Study of the Efficacy and Pharmacogenomics of Cladribine-based Salvage Chemotherapy in Patients With Relapse/Refractory and Secondary Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)[NCT03150004] | Phase 2 | 90 participants (Anticipated) | Interventional | 2017-06-14 | Recruiting |
| A Phase 1/2 Open-Label Study to Assess the Safety, Tolerability, and Pharmacokinetics of Intravenous Infusion of MB07133 in Subjects With Unresectable Hepatocellular Carcinoma and Child-Pugh Class A Liver Function[NCT00073736] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2003-09-30 | Completed |
| A Phase I Trial Evaluating the Effect of the Addition of HMGCoA-Reductase Inhibition With Pravastatin to Salvage Chemotherapy Idarubicin-HDAC in Patients With Relapsed or Refractory Acute Myelogenous Leukemia[NCT00107523] | Phase 1 | 0 participants | Interventional | 2005-01-31 | Completed |
| Intensive Induction for Newly Diagnosed Acute Myelogenous Leukemia[NCT00274807] | Phase 2 | 40 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse[NCT00112554] | Phase 3 | 420 participants (Anticipated) | Interventional | 2005-03-31 | Completed |
| Phase 2 Study of Imatinib-Combined Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia[NCT00130195] | Phase 2 | 100 participants (Actual) | Interventional | 2002-09-30 | Completed |
| A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Myeloid Malignancies[NCT04778410] | Phase 2 | 59 participants (Anticipated) | Interventional | 2021-06-28 | Active, not recruiting |
| Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia[NCT06001788] | Phase 1 | 171 participants (Anticipated) | Interventional | 2023-12-31 | Recruiting |
| Phase II Study Of Rituximab And Short Duration, High Intensity Chemotherapy With G-CSF Support In Previously Untreated Patients With Burkitt Lymphoma/Leukemia[NCT00039130] | Phase 2 | 105 participants (Actual) | Interventional | 2002-05-31 | Completed |
| A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytar[NCT00093600] | Phase 1 | 69 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia[NCT00124644] | Phase 1 | 30 participants | Interventional | 2006-03-31 | Terminated(stopped due to "Withdrawn due to toxicity problems") |
| A Single-arm Open-label Multicenter Clinical Study of Selinexor in Combination With HAD or CAG Rregimens in Relapsed or Refractory Acute Myeloid Leukemia[NCT05726110] | Phase 3 | 50 participants (Anticipated) | Interventional | 2023-01-29 | Recruiting |
| Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia[NCT00343369] | | 550 participants (Anticipated) | Interventional | 2003-01-31 | Recruiting |
| A Phase I And Pharmacological Trial Of 17-Allylamino -17-demethoxygeldanamycin (17-AAG) And Cytarabine In Refractory Leukemia And Myelodysplastic Syndrome[NCT00098423] | Phase 1 | 42 participants (Actual) | Interventional | 2004-11-30 | Completed |
| A Phase I Study Of Therapy With The Farnesyl Transferase Inhibitor R115777 (Zarnestra) Combined With Conventional Induction And Consolidation Chemotherapy For Previously Untreated Patients Over Age 55 With Acute Myeloid Leukemia (AML)[NCT00101153] | Phase 1 | 24 participants (Actual) | Interventional | 2007-04-30 | Completed |
| Phase I Study of Adoptive Immunotherapy With CD8 Minor Histocompatibility (H) Antigen-Specific CTL Clones for Patients With Relapsed of AML or ALL After Allogeneic Hematopoietic Stem Cell Transplant[NCT00107354] | Phase 1 | 0 participants | Interventional | 1998-12-31 | Completed |
| Randomized Prospective Study of Adding Lomustine to Idarubicin and Cytarabine for Induction Chemotherapy and Adding Intermediate Dose Cytarabine to Consolidation in Older Patients With Acute Myeloid Leukaemia[NCT00480064] | Phase 3 | 360 participants (Actual) | Interventional | 1995-07-31 | Completed |
| Phase II Study: 2-Chlorodeoxyadenosine (2-CdA) and Cytarabine (Ara-C) in Idiopathic Hypereosinophilic Syndrome (HES)[NCT00483067] | Phase 2 | 13 participants (Actual) | Interventional | 1998-03-31 | Completed |
| A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT01154439] | Phase 1 | 11 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Phase I Study to Evaluate the Safety and Efficacy of NK Cell Therapy in Acute Myeloid Leukemia (AML).[NCT05987696] | Phase 1 | 102 participants (Anticipated) | Interventional | 2023-08-10 | Not yet recruiting |
| Pilot Study in AIDS-Related Lymphomas[NCT00002524] | Phase 2 | 46 participants (Actual) | Interventional | 1993-06-30 | Completed |
| Phase 2 Study of 5 Days Azacytidine Priming Prior to Fludarabine, Cytarabine and Granulocyte-Colony Stimulating Factor (G-CSF) Combination for Patients With Relapsed or Refractory AML[NCT02275663] | Phase 2 | 37 participants (Anticipated) | Interventional | 2014-12-31 | Recruiting |
| Phase II Study on Gemtuzumab Ozogamicin in Combination With All-trans-Retinoic Acid, High-dose Cytarabine and Mitoxantrone in Patients With Primary Refractory Acute Myeloid Leukemia[NCT00143975] | Phase 2 | 95 participants (Actual) | Interventional | 2004-06-30 | Completed |
| An Open-Label, Dose Escalation, Phase 1 Study of PEVONEDISTAT, a Novel Inhibitor of the NEDD8-Activating Enzyme (NAE), in Combination With Low Dose Cytarabine (LDAC) in Adult Patients With Acute Myelogenous Leukemia (AML) and Advanced Myelodysplastic Synd[NCT03459859] | Phase 1 | 12 participants (Actual) | Interventional | 2018-05-21 | Completed |
| HLA-mismatched Allogeneic Cellular Therapy (HMMACT) After Chemotherapy in High Risk Acute Myeloid Leukemia[NCT01801046] | Phase 1 | 10 participants (Actual) | Interventional | 2013-03-06 | Terminated(stopped due to Insufficient Accrual) |
| A Phase 2 Study of Fludarabine, Cytarabine, Filgrastim-sndz,Gemtuzumab Ozogamicin and Idarubicin in Newly Diagnosed Core Binding Factor Associated Acute Myelogenous Leukemia[NCT00801489] | Phase 2 | 270 participants (Anticipated) | Interventional | 2007-04-04 | Recruiting |
| A Randomized, Multicenter, Open-Label Study of Single Dose Filgrastim-SD/01 Versus Daily Filgrastim Following ESHAP Chemotherapy for Non-Hodgkin's Lymphoma[NCT00004192] | Phase 2 | 60 participants (Anticipated) | Interventional | 2000-05-01 | Completed |
| A Randomized Trial to Evaluate Early High Dose Therapy and Autologous Bone Marrow Transplantation as Part of Planned Initial Therapy for Poor Risk Intermediate/High Grade NHL[NCT00003578] | Phase 3 | 500 participants (Anticipated) | Interventional | 1993-01-31 | Active, not recruiting |
| A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies[NCT00382590] | Phase 2 | 11 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Randomized Trial Using Standard Dose Versus High Dose Rituximab in Addition to Autologous Transplantation With BEAM for Patients With Diffuse Large B Cell Lymphomas[NCT00472056] | Phase 2 | 93 participants (Actual) | Interventional | 2005-03-31 | Completed |
| A Phase I/II Trial of ABT-751 Combined With Dexamethasone, PEG-asparaginase, and Doxorubicin in Relapsed Acute Lymphoblastic Leukemia (ALL)[NCT00439296] | Phase 1/Phase 2 | 9 participants (Actual) | Interventional | 2006-05-22 | Terminated(stopped due to The study was stopped due to poor accrual and lack of funding.) |
| "Randomized Phase I/II Study of 5-Azacytidine in Combination With Cytosine Arabinoside in Patients With Relapsed/Refractory Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome - SPORE"[NCT00569010] | Phase 1/Phase 2 | 36 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Phase IIB, Multicenter, Randomized, Open Label Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients With Untreated AML 60-75 Years of Age.[NCT00788892] | Phase 2 | 126 participants (Actual) | Interventional | 2008-10-31 | Completed |
| Study of Oral Clofarabine Plus Low-dose Cytarabine in Previously Treated AML and High-Risk MDS Patients at Least 60 Years of Age[NCT00839982] | Phase 1/Phase 2 | 35 participants (Actual) | Interventional | 2008-11-30 | Completed |
| Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)[NCT00928200] | Phase 1 | 1 participants (Actual) | Interventional | 2009-04-13 | Terminated(stopped due to Study was terminated due to lack of accrual.) |
| Sequential Autologous HCT / Nonmyeloablative Allogeneic HCT Using Related, HLA-Haploidentical Donors for Patients With High-Risk Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia[NCT01008462] | Phase 2 | 16 participants (Actual) | Interventional | 2010-03-18 | Completed |
| A Phase 2 Study of Clofarabine, Idarubicin, Cytarabine, Vincristine, and Corticosteroids for Patients With Newly Diagnosed or Relapsed Mixed Phenotype Acute Leukemia[NCT02135874] | Phase 2 | 18 participants (Actual) | Interventional | 2014-10-27 | Completed |
| Phase II Study of Hyper-CVAD Plus Nelarabine in Previously Untreated T-ALL and Lymphoblastic Lymphoma[NCT00501826] | Phase 2 | 160 participants (Anticipated) | Interventional | 2007-07-11 | Recruiting |
| Multicenter,Open Label,Phase 2 Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia[NCT06068621] | Phase 2 | 200 participants (Anticipated) | Interventional | 2023-08-01 | Recruiting |
| A Phase 1b Study With Expansion Cohort of Escalating Doses of KRT-232 (AMG 232) Administered in Combination With Standard Induction Chemotherapy (Cytarabine and Idarubicin) in Newly Diagnosed Acute Myelogenous Leukemia (AML)[NCT04190550] | Phase 1 | 24 participants (Anticipated) | Interventional | 2021-02-04 | Active, not recruiting |
| A Pilot, Pharmacodynamic Correlate, Multi-Institutional Trial of Sirolimus in Combination With Chemotherapy (Mitoxantrone, Etoposide, Cytarabine) for the Treatment of High Risk, Acute Myelogenous Leukemia[NCT01184898] | | 36 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia[NCT01363128] | Phase 2 | 72 participants (Actual) | Interventional | 2011-07-12 | Completed |
| Autologous Stem Cell Transplant In Patients With Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphomas (NHL)[NCT03125642] | Phase 2 | 150 participants (Anticipated) | Interventional | 2017-04-20 | Recruiting |
| BLockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia 1 (BLAST MRD AML-1): A Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination With Conventional Intensive Chemotherapy as F[NCT04214249] | Phase 2 | 124 participants (Anticipated) | Interventional | 2021-02-17 | Recruiting |
| Treatment Of Newly Diagnosed Adult Acute Lymphoblastic Leukemia With Intensified Post Remission Therapy Containing PEG-Asparaginase.[NCT00184041] | Phase 2 | 47 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Early Assessment of Treatment Response in AML Using FLT PET/CT Imaging[NCT02392429] | Phase 2 | 57 participants (Anticipated) | Interventional | 2016-04-20 | Active, not recruiting |
| Phase II Study to Evaluate the Efficacy of Upfront Obinutuzumab in Mantle Cell Lymphoma Patients Treated by DHAP Followed by Autologous Transplantation Plus Obinutuzumab Maintenance Then MRD Driven Maintenance[NCT02896582] | Phase 2 | 86 participants (Actual) | Interventional | 2016-10-31 | Active, not recruiting |
| Total Therapy Study XIV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia[NCT00187005] | Phase 3 | 53 participants (Actual) | Interventional | 1998-07-31 | Terminated(stopped due to Toxicity) |
| A Phase I-II Study of the Combination of Ruxolitinib or Dasatinib With Chemotherapy in Patients With Philadelphia Chromosome (Ph)-Like Acute Lymphoblastic Leukemia (ALL)[NCT02420717] | Phase 2 | 11 participants (Actual) | Interventional | 2015-07-15 | Terminated(stopped due to Study was closed early due to low accrual and lack of response.) |
| Phase I/II Study of Arsenic Trioxide in Combination With Cytosine Arabinoside in Patients With High-risk Myelodysplastic Syndrome and Poor-prognosis Acute Myelogenous Leukemia[NCT00195104] | Phase 1/Phase 2 | 87 participants (Actual) | Interventional | 2003-09-17 | Completed |
| Randomized Phase II Trial on Primary Chemotherapy With High-dose Methotrexate, Alone or Associated With High-dose Cytarabine, Followed by Response- and Age-tailored Radiotherapy for Immunocompetent Patients With Newly Diagnosed Primary Central Nervous Sys[NCT00210314] | Phase 2 | 79 participants (Actual) | Interventional | 2003-07-31 | Completed |
| A Phase 1 Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT06177067] | Phase 1 | 24 participants (Anticipated) | Interventional | 2024-01-31 | Not yet recruiting |
| Prospective Pilot Trial of Arsenic Trioxide (Trisenox®) in Combination With Cytosine Arabinoside in Patients With Advanced or Transformed Myelofibrosis[NCT00572065] | Early Phase 1 | 21 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Study of the Efficacy and Safety of Venetoclax Plus Azacytidine Versus Daunorubicin Plus Cytarabine in Adult Acute Myeloid Leukemia (AML) Patients With Adverse Risk Features[NCT05939180] | Phase 2/Phase 3 | 108 participants (Anticipated) | Interventional | 2023-07-01 | Recruiting |
| A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed Acute Promyelocytic Leukemia (APL)[NCT00591526] | Phase 3 | 250 participants (Actual) | Interventional | 2000-06-30 | Completed |
| Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming With Decitabine in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS): A Phase 1/2 Study[NCT01729845] | Phase 1/Phase 2 | 52 participants (Actual) | Interventional | 2012-12-20 | Completed |
| Phase III Trial in AML Comparing Standard-dose vs High-dose Remission Induction and, Within a Risk-oriented Postremission Strategy, Autologous Blood Stem Cell Transplantation vs Blood Stem Cell-supported Multicycle High-dose Program[NCT00495287] | Phase 3 | 573 participants (Actual) | Interventional | 2006-11-30 | Completed |
| A Phase 1 Study of Azacitidine in Combination With MEC (Mitoxantrone, Etoposide, Cytarabine) in Relapsed and Refractory Acute Myeloid Leukemia[NCT01249430] | Phase 1 | 24 participants (Actual) | Interventional | 2011-01-20 | Completed |
| A Pilot Study of the Efficacy of the Chop-Montak Regimen in Patients With Newly Diagnosed Peripheral T Cell Lymphoma[NCT00513188] | | 0 participants (Actual) | Interventional | 2007-02-28 | Withdrawn |
| Phase II Trial of CLAG-M in Relapsed ALL[NCT01513603] | Phase 2 | 50 participants (Anticipated) | Interventional | 2012-01-31 | Recruiting |
| Intergroup Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Evaluation of Rituximab Efficacy and Safety in High Risk Patients - Phase III Trial[NCT01516580] | Phase 3 | 482 participants (Actual) | Interventional | 2011-12-31 | Active, not recruiting |
| A Phase II Study of Microtransplantation in Patients With Refractory or Relapsed Hematologic Malignancies[NCT02433483] | Phase 2 | 4 participants (Actual) | Interventional | 2015-05-22 | Terminated(stopped due to The study was closed due to poor accrual and because of competing protocols.) |
| Phase I/II Study on Cytarabine and Idarubicin Combined With Escalating Doses of Clofarabine as Induction Therapy in Patients With Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10)[NCT01534702] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2012-01-31 | Recruiting |
| [NCT01540812] | | 418 participants (Actual) | Observational | 2012-02-29 | Completed |
| Hyper-CVAD With Liposomal Vincristine (Hyper-CMAD) in Acute Lymphoblastic Leukemia[NCT01319981] | Phase 2 | 31 participants (Actual) | Interventional | 2013-03-05 | Completed |
| A RANDOMIZED TRIAL OF UNMODIFIED VERSUS T-CELL DEPLETED ALLOGENEIC HLA-IDENTICAL BONE MARROW TRANSPLANTATION FOR THE TREATMENT OF ACUTE LEUKEMIAS[NCT00002534] | Phase 3 | 0 participants | Interventional | 1993-05-31 | Completed |
| A Phase III Study of Large Cell Lymphomas in Children and Adolescents: Comparison of APO vs APO + IDMTX/HDARA-C and Continuous vs Bolus Infusion of Doxorubicin[NCT00002618] | Phase 3 | 242 participants (Anticipated) | Interventional | 1994-12-31 | Completed |
| Randomized Comparisons of Oral Mercaptopurine vs Oral Thioguanine and IT Methotrexate vs ITT for Standard Risk Acute Lymphoblastic Leukemia[NCT00002744] | Phase 3 | 1,970 participants (Actual) | Interventional | 1996-05-31 | Completed |
| Induction Intensification in Infant ALL: A Children's Oncology Group Study[NCT00002756] | Phase 2 | 221 participants (Actual) | Interventional | 1996-06-30 | Completed |
| Phase II Study of Intrathecal Therapy With DepoCyt for Active Lymphomatous or Leukemic Meningitis[NCT00523939] | Phase 2 | 4 participants (Actual) | Interventional | 2006-06-30 | Terminated(stopped due to Low accrual.) |
| Phase III Study of Combination Chemotherapy in Children With T Cell and Pre-B Cell Non-Hodgkin's Lymphoma[NCT00003650] | Phase 3 | 179 participants (Actual) | Interventional | 1997-02-28 | Completed |
| Evaluating the MBVP Chemotherapy Schedule Followed by Consolidating Radiotherapy in Non-AIDS Related Primary Central Nervous System Lymphoma (NAPCL)[NCT00003061] | Phase 2 | 50 participants (Anticipated) | Interventional | 1997-07-31 | Completed |
| A Phase I Dose Escalation Study of Intrathecal DepoFoam Encapsulated Cytarabine (DTC 101) in Pediatric Patients With Advanced Meningeal Malignancies[NCT00003073] | Phase 1 | 15 participants (Anticipated) | Interventional | 1997-02-28 | Active, not recruiting |
| BEAM Plus Iodine-131 Anti-B1 Antibody and Autologous Hematopoietic Stem Cell Transplantation for Treatment of Recurrent Diffuse Large B-Cell Non-Hodgkin's Lymphoma[NCT00006695] | Phase 2 | 50 participants (Actual) | Interventional | 2000-04-01 | Completed |
| A Pilot Study of Dose Intensification of Methotrexate and Cyclophosphamide in Patients With Advanced-Stage (III/IV) Small Non-Cleaved Non-Hodgkins Lymphoma and B-Cell All- A Limited Institution Phase III Pilot Study[NCT00003217] | Phase 1 | 20 participants (Actual) | Interventional | 1998-03-31 | Completed |
| Transplantation of Unrelated Donor Hematopoietic Stem Cells for the Treatment of Hematological Malignancies[NCT00281879] | Phase 2 | 200 participants (Actual) | Interventional | 2006-02-28 | Terminated |
| MULTICENTRE TRIAL OF INTENSIFIED THERAPY FOR ADULT ALL (O5/93)[NCT00002531] | Phase 2 | 0 participants | Interventional | 1993-01-31 | Active, not recruiting |
| Phase II Trial of Sequential Modification of Immunosuppression, Interferon Alpha, and Promace-Cytabom For Treatment of Post-Cardiac Transplant Lymphoproliferation.[NCT00002657] | Phase 2 | 20 participants (Actual) | Interventional | 1995-05-31 | Completed |
| A Study of Modified Augmented BFM Therapy for Infants With Acute Lymphoblastic Leukemia[NCT00022126] | Phase 2 | 6 participants (Actual) | Interventional | 2002-11-30 | Completed |
| A Phase II Study of Bevacizumab (rhuMab VEGF, NSC 704865), Idarubicin and Cytarabine in Patients With Chronic Myeloid Leukemia in Blast Phase[NCT00023920] | Phase 2 | 60 participants (Actual) | Interventional | 2001-07-31 | Terminated(stopped due to Administratively complete.) |
| A Randomized Trial Of BEAM Plus PBSCT Versus Single Agent High-Dose Therapy Followed By BEAM Plus PBSCT In Patients With Relapsed Hodgkin's Disease[NCT00025636] | Phase 3 | 220 participants (Anticipated) | Interventional | 2001-07-31 | Active, not recruiting |
| Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission[NCT00027547] | Phase 1/Phase 2 | 0 participants | Interventional | 2001-07-31 | Completed |
| A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent[NCT02019069] | Phase 2 | 11 participants (Actual) | Interventional | 2014-02-03 | Completed |
| A Randomised Phase III Study On The Effect Of The Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) During Sequential Chemotherapy Followed By Autologous Stem Cell Transplantation In Patients With Relapse B-Cell Non-Hodgkin Lymphoma(HOVON 44 STUDY)[NCT00012051] | Phase 3 | 340 participants (Anticipated) | Interventional | 2000-09-30 | Completed |
| Phase I Trial of mBACOD and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in AIDS-Associated Large Cell, Immunoblastic, and Small Non-cleaved Lymphoma[NCT00000689] | Phase 1 | 18 participants | Interventional | | Completed |
| A Phase I/II Trial of STI571 and High-Dose Cytarabine in Myeloid Blast Crisis of Chronic Myeloid Leukemia[NCT00015834] | Phase 1/Phase 2 | 46 participants (Actual) | Interventional | 2001-05-31 | Completed |
| International Collaborative Treatment Protocol for Infants Under One Year With Acute Lymphoblastic Leukemia[NCT00015873] | Phase 3 | 350 participants (Anticipated) | Interventional | 1999-05-31 | Completed |
| A Phase II Study of the Recombinant Human Monoclonal Anti-Vascular Endothelial Growth Factor Antibody (rhuMAB VEGF) Bevacizumab (NSC #704865, IND # 7,921) Administered in Times Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for [NCT00015951] | Phase 2 | 0 participants | Interventional | 2001-04-30 | Completed |
| The Use of Modified BFM +/- Compound 506U78 (Nelarabine) (NSC# 686673, IND #52611) in an Intensive Chemotherapy Regimen for the Treatment of T-Cell Leukemia[NCT00016302] | | 100 participants (Actual) | Interventional | 2001-04-30 | Completed |
| Treatment of Mantle Cell Lymphomas at Advanced Stages: Prospective Randomized Comparison of Myeloablative Radiochemotherapy Followed by Blood Stem Cell Transplantation Versus Maintenance With Interferon Alpha in First Remission After Initial Cytoreductive[NCT00016887] | Phase 3 | 0 participants | Interventional | 2000-12-31 | Active, not recruiting |
| A Clinicopathological Study In Burkitts's And Burkitt-Like Non-Hodgkin's Lymphoma[NCT00040690] | Phase 2 | 120 participants (Anticipated) | Interventional | 2008-11-30 | Completed |
| Autologous Peripheral Blood Stem Cell Transplant for Patients With Lymphoma[NCT00345865] | Phase 2 | 473 participants (Actual) | Interventional | 2005-08-24 | Completed |
| A Phase I Study of Triapine and Cytarabine in Patients With Hematologic Malignancies[NCT00064090] | Phase 1 | 0 participants | Interventional | 2003-03-31 | Completed |
| Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study[NCT00070174] | Phase 2 | 350 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Combination Chemotherapy (Methotrexate, Procarbazine And CCNU), Intraventricular Cytarabine And Methotrexate, +/- Intra-Ocular Chemotherapy For Patients With Primary Central Nervous System Lymphoma[NCT00074191] | Phase 2 | 1 participants (Actual) | Interventional | 2000-01-31 | Completed |
| Open Label, Phase II Dosing Study of Ara-C Chemotherapy in Combination With EL625 and Idarubicin in Refractory and Relapsed Acute Myelogenous Leukemia (AML)[NCT00074737] | Phase 2 | 53 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Idarubicin and Ara-C in Combination With Gemtuzumab-Ozogamicin (IAGO) for Young Untreated Patients, Without an HLA Identical Sibling, With High Risk MDS or AML Developing After a Preceding Period With MDS During 6 Months Duration: A Phase II Study[NCT00077116] | Phase 2 | 31 participants (Actual) | Interventional | 2003-11-30 | Completed |
| Randomized Study of ICE Plus RITUXIMAB Versus DHAP Plus Rituximab in Previously Treated Patients With Diffuse Large B-cell Lymphoma, Followed by Randomized Maintenance With Rituximab[NCT00137995] | Phase 3 | 481 participants (Actual) | Interventional | 2003-06-30 | Completed |
| Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived NK Cells Combined With Rituximab High-Dose Chemotherapy and Autologous Stem Cell Transplant for B-Cell Non-Hodgkin's Lymphoma[NCT03019640] | Phase 2 | 22 participants (Actual) | Interventional | 2017-10-10 | Completed |
| Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006), an Oral Vascular Endothelial Growth Factor (VEGF), Rapidly Accelerated Fibrosarcoma (RAF) and FMS-like Tyrosine Kinase 3 (FLT3), in Patients With High-risk MDS and AML[NCT00542971] | Phase 1/Phase 2 | 78 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Treatment Protocol for T-Cell and B-Precursor Cell Lymphoblastic Lymphoma of the European Inter-group Co-operation on Childhood Non-Hodgkin-Lymphoma (EICNHL)[NCT00275106] | Phase 3 | 600 participants (Anticipated) | Interventional | 2004-09-30 | Terminated(stopped due to Withdrawn due to an excess of toxic deaths) |
| A Phase I/II Study of Flavopiridol (NSC 649890, IND 46,211) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Poor-Risk Acute Leukemias[NCT00016016] | Phase 1/Phase 2 | 53 participants (Anticipated) | Interventional | 2001-02-28 | Completed |
| An Open-Label, Phase I/II, Multicenter Dose Escalation Study of Zosuquidar, Daunorubicin, and Cytarabine in Patients Ages 55-75 With Newly Diagnosed Acute Myeloid Leukemia[NCT00129168] | Phase 1/Phase 2 | 100 participants (Anticipated) | Interventional | 2005-08-31 | Completed |
| PILOT MULTINATIONAL PROTOCOLS IN ACUTE LYMPHOBLASTIC LEUKEMIA AND DIFFUSE NON-HODGKIN'S LYMPHOMA[NCT00018954] | Phase 2 | 0 participants | Interventional | 1992-10-31 | Completed |
| A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma[NCT00020943] | Phase 2 | 79 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Children's Oncology Group Pilot Study for the Treatment of Very High Risk Acute Lymphoblastic Leukemia in Children and Adolescents (Imatinib (STI571, GLEEVEC) NSC#716051)[NCT00022737] | Phase 3 | 220 participants (Actual) | Interventional | 2002-10-31 | Completed |
| Phase II Window Evaluation of the Farnesyl Transferase Inhibitor (R115777) Followed by 13-CIS Retinoic Acid, Cytosine Arabinoside and Fludarabine Plus Hematopoietic Stem Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia[NCT00025038] | Phase 2 | 100 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Dose Finding Study of the Safety of Gemtuzumab Ozogamicin Combined With Conventional Chemotherapy for Patients With Relapsed or Refractory Acute Myeloid Leukemia[NCT00028899] | Phase 1 | 47 participants (Actual) | Interventional | 2002-07-31 | Completed |
| A Randomized Clinical Study to Determine the Patient Benefit and Safety of Depocyt (Cytarabine Liposome Injection) for the Treatment of Neoplastic Meningitis[NCT00029523] | Phase 4 | 100 participants | Interventional | 2001-04-30 | Completed |
| A Dose Ranging Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) Given in Combination With Cytarabine in Relapsed or Refractory Patients and Alder De Novo Patients With Acute Myeloid Leukemia.[NCT00037596] | Phase 2 | 0 participants | Interventional | 2000-08-31 | Completed |
| Campath 1H (Alemtuzumab) Combined With High-Dose Therapy and Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia[NCT00276809] | Phase 2 | 30 participants (Anticipated) | Interventional | 2001-06-30 | Completed |
| A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age[NCT00039117] | Phase 1 | 32 participants (Actual) | Interventional | 2002-04-30 | Completed |
| A Randomized Study of Two Methods of CNS Prophylaxis in Patients With Acute Lymphoblastic Leukemia[NCT00019409] | Phase 3 | 0 participants (Actual) | Interventional | 1999-10-31 | Withdrawn |
| A Phase II Study of Gemtuzumab Ozogamicin (Mylotarg) and Standard Dose ARA-C for Patients With Relapsed Acute Myeloid Leukemia (AML)[NCT00049179] | Phase 2 | 33 participants (Actual) | Interventional | 2003-04-30 | Completed |
| Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia (ALL) Who Experience a Bone Marrow Relapse[NCT00049569] | | 126 participants (Anticipated) | Interventional | 2003-01-31 | Completed |
| A Phase II Study Of Daunomycin And ARA-C, Both Given By Continous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) In Patients Of Age 56 Or Older[NCT00023777] | Phase 2 | 71 participants (Actual) | Interventional | 2001-08-31 | Completed |
| Gemtuzumab Ozogamicin (GO) Combined With Standard Intensive Chemotherapy Versus Standard Intensive Chemotherapy Alone For Induction/Consolidation In Patients 61-75 Years Old With Previously Untreated AML: A Randomized Phase III Trial (AML-17) Of The EORTC[NCT00052299] | Phase 3 | 472 participants (Actual) | Interventional | 2002-09-30 | Completed |
| A Dose-ranging Phase I/II Study of STI571 in Combination With Cytarabin in Patients With First Chronic Phase Chronic Myeloid Leukemia[NCT00028847] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2001-04-30 | Active, not recruiting |
| A Phase II Study of Rituximab (IND #7028) and Ifosfamide, Carboplatin and Etoposide (ICE) Chemotherapy in Children With Recurrent/Refractory B-cell (CD20+) Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia[NCT00058461] | Phase 2 | 82 participants (Anticipated) | Interventional | 2003-11-30 | Terminated |
| Cytarabine Plus Continuous Infusion Daunorubicin Induction Therapy for Adults With Acute Myeloid Leukemia: A Feasibility Study With Cardiac MRI Monitoring[NCT02971397] | Phase 2 | 40 participants (Actual) | Interventional | 2016-11-30 | Active, not recruiting |
| A Phase II Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin (BSHAP) as Salvage in Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma[NCT00069966] | Phase 2 | 0 participants | Interventional | 2003-04-30 | Active, not recruiting |
| Randomised Controlled Study Comparing Fast Track and Standard Care Protocol on the Functional Outcomes and Hospital Stay of Total Knee Arthroplasty[NCT03869996] | | 64 participants (Anticipated) | Interventional | 2019-02-25 | Recruiting |
| A Phase I Study of GTI2040 (NSC 722929; IND 67368) in Combination With High-dose Cytarabine in Refractory or Relapsed Acute Myeloid Leukemia (AML)[NCT00070551] | Phase 1 | 51 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Protocol for the Treatment of Adults Aged NCT00209833] | Phase 2/Phase 3 | 200 participants | Interventional | 1999-01-31 | Active, not recruiting |
| A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic M[NCT00219739] | Phase 3 | 789 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Combination Chemotherapy (Methotrexate, Cyclophosphamide, And Etoposide Phosphate) Delivered In Conjunction With Osmotic Blood-Brain Barrier Disruption (BBBD), With Intraventricular Cytarabine +/- Intra-Ocular Chemotherapy, In Patients With Primary Centra[NCT00074178] | Phase 2 | 22 participants (Actual) | Interventional | 2000-01-31 | Completed |
| Phase 2 Study of Applying Pediatric Regimens to Younger Adult Patients With BCR-ABL-Negative Acute Lymphoblastic Leukemia[NCT00131053] | Phase 2 | 120 participants (Anticipated) | Interventional | 2002-09-30 | Recruiting |
| T-Cell Depleted, Reduced-Intensity Allogeneic Stem Cell Transplantation From Haploidentical Related Donors For Hematologic Malignancies[NCT00080925] | Phase 1 | 20 participants (Anticipated) | Interventional | 2004-02-29 | Completed |
| A Phase I Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin in the Treatment of Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma[NCT00053105] | Phase 1 | 0 participants | Interventional | 2002-02-28 | Active, not recruiting |
| Irinotecan And Cytarabine In Refractory or Relapsed Acute Myeloid Leukemia And In Chronic Myelogenous Leukemia In Myeloid Blast Transformation: Efficacy And In Vitro Correlates[NCT00053144] | Phase 1 | 0 participants | Interventional | 1999-11-30 | Completed |
| Treatment of Acute Lymphoblastic Leukemia in Children[NCT00165178] | Phase 3 | 498 participants (Actual) | Interventional | 2000-09-30 | Completed |
| Treatment Optimization Trial in Chronic Myeloid Leukemia (CML) - Randomized Controlled Comparison of Imatinib vs. Imatinib/Interferon-alpha vs. Imatinib/Low-Dose AraC vs. Interferon-alpha Standard Therapy and Determination of the Role of Allografting in N[NCT00055874] | Phase 3 | 1,551 participants (Actual) | Interventional | 2002-06-30 | Completed |
| AML96 - Risk-Adapted and Randomized Postremission-Therapy for Adult Acute Myeloid Leukemia Patients. A Cooperative AML-Study of the German SHG-Study Group.[NCT00180115] | Phase 4 | 400 participants | Interventional | 1996-02-29 | Completed |
| A Phase I Trial Combining IDEC-Y2B8 And High-Dose Beam Chemotherapy With Hematopoietic Progenitor Cell Transplant In Patients With Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma[NCT00058292] | Phase 1 | 44 participants (Actual) | Interventional | 2000-04-30 | Completed |
| Prospective Study of the Diagnosis and Treatment of Myelodysplastic Syndromes (MDS) in Childhood[NCT00047268] | Phase 3 | 0 participants | Interventional | 1998-07-31 | Active, not recruiting |
| A Multicenter, Phase 2 Study, to Evaluate Safety and Efficacy of an Acute Lymphoblastic Leukemia (ALL) Intensive Chemotherapy for Adult Lymphoblastic Lymphoma (LL).[NCT00195871] | Phase 2 | 155 participants (Actual) | Interventional | 2004-02-29 | Active, not recruiting |
| A Randomized, Multicenter Open Label Phase II Study to Determine the Safety and Efficacy of Induction Therapy With Imatinib in Comparison With Standard Induction Chemotherapy in Elderly (> 55 Years) Patients With Ph Positive Acute Lymphoblastic Leukemia ([NCT00199186] | Phase 2 | 0 participants | Interventional | 2002-03-31 | Recruiting |
| ALL Adult Consortium Trial: Adult ALL Trial[NCT00476190] | Phase 2 | 112 participants (Anticipated) | Interventional | 2007-04-30 | Active, not recruiting |
| Azacitidine Compared to Conventional Chemotherapy in Consolidation of Elderly Patients (65 Years or Older) With AML in First Complete Remission[NCT01794169] | Phase 2 | 130 participants (Anticipated) | Interventional | 2013-03-31 | Terminated(stopped due to Poor recruitment) |
| An Intergroup Phase II Clinical Trial for Adolescents and Young Adults With Untreated Acute Lymphoblastic Leukemia (ALL)[NCT00558519] | Phase 2 | 318 participants (Actual) | Interventional | 2008-03-12 | Active, not recruiting |
| Epigenetic Reprogramming in Relapse AML: A Phase 1 Study of Decitabine and Vorinostat Followed by Fludarabine, Cytarabine and G-CSF (FLAG) in Children and Young Adults With Relapsed/Refractory AML[NCT02412475] | Phase 1 | 3 participants (Actual) | Interventional | 2015-02-21 | Terminated(stopped due to We opened a competing study with the TACL consortium) |
| Medical Research Council Working Party on Leukaemia in Children UK National Lymphoblastic Leukaemia (ALL) Trial[NCT00003437] | Phase 3 | 1,800 participants (Anticipated) | Interventional | 1997-01-31 | Active, not recruiting |
| Treatment of Children With Down Syndrome (DS) and Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Transient Myeloproliferative Disorder (TMD): A Phase III Group-Wide Study[NCT00003593] | Phase 3 | 254 participants (Actual) | Interventional | 1999-06-30 | Completed |
| A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia, Aggressive, Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia[NCT00472849] | Phase 1/Phase 2 | 92 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias[NCT00410423] | Phase 1/Phase 2 | 55 participants (Actual) | Interventional | 2006-01-31 | Completed |
| A Randomized Multi-Center Treatment Study (COALL 08-09) to Improve the Survival of Children With Acute Lymphoblastic Leukemia on Behalf of the German Society of Pediatric Hematology and Oncology[NCT01228331] | Phase 2/Phase 3 | 745 participants (Actual) | Interventional | 2010-10-31 | Active, not recruiting |
| A Prospective, Multicenter, Single Arm Clinical Study to Evaluate Efficacy of HAD Induction With Intensified Cytarabine in Newly-diagnosed CEBPA Double Mutated Acute Myeloid Leukemia[NCT04415008] | Phase 2 | 40 participants (Anticipated) | Interventional | 2020-06-01 | Recruiting |
| Efficacy of Intermediate-Dose Cytarabine Induction Regimen in Adult AML[NCT03021330] | Phase 3 | 1,100 participants (Anticipated) | Interventional | 2017-02-08 | Recruiting |
| Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation[NCT00609739] | Phase 1/Phase 2 | 1 participants (Actual) | Interventional | 1999-06-30 | Terminated(stopped due to Low accrual) |
| T-Regulatory Cell Kinetics Post Transplant For Patients Undergoing Matched Sibling Stem Cell Transplantation[NCT00578461] | | 26 participants (Actual) | Interventional | 2007-10-31 | Terminated |
| T-Regulatory Cell Kinetics for Patients Receiving Alemtuzamb and Undergoing Stem Cell Transplantation From HLA Mismatched-Related, or HLA Matched, or One Antigen Mismatched-Unrelated Donors[NCT00578539] | | 24 participants (Actual) | Interventional | 2007-10-31 | Terminated |
| A Phase II Study of Combination Nilotinib and Hyper-CVAD in Patients Newly Diagnosed With Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia Blast-Phase Lymphoid Lineage[NCT01670084] | Phase 2 | 0 participants (Actual) | Interventional | 2012-12-31 | Withdrawn(stopped due to No Accrual) |
| A Phase II Study of Doxil (Liposomal Doxorubicin), Cyclophosphamide, Vincristine and Prednisone for AIDS-Related Systemic Lymphoma[NCT00003388] | Phase 2 | 38 participants (Anticipated) | Interventional | 1999-07-26 | Completed |
| Treatment Regimen or Children or Adolescent With Mature B-cell NHL or B-AL in China[NCT02405676] | Phase 2/Phase 3 | 200 participants (Anticipated) | Interventional | 2015-01-31 | Active, not recruiting |
| An Open-label, Multi-center Phase Ib/II Study to Evaluate the Tolerance and Efficacy of Mitoxantrone Hydrochloride Liposome Injection Combined With Cytarabine in Patients With Acute Myeloid Leukemia (AML)[NCT05100303] | Phase 1/Phase 2 | 58 participants (Anticipated) | Interventional | 2021-12-31 | Not yet recruiting |
| Asia-wide, Multicenter Open-label, Phase II Non-randomised Study Involving Children With Down Syndrome Under 21 Year-old With Newly Diagnosed, Treatment naïve Acute Lymphoblastic Leukemia[NCT03286634] | Phase 2 | 60 participants (Anticipated) | Interventional | 2017-04-18 | Recruiting |
| A Non-Myeloablative Conditioning Regimen for Allogeneic Transplantation With Clofarabine, Cytarabine, and Thymoglobulin for Myelodysplastic Syndrome and Acute Myeloid Leukemia[NCT00593645] | Phase 2 | 7 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to toxicities were worse than expected) |
| The Efficiency of CAMS-2016 Trial for the Newly Diagnosed Pediatric Acute Myeloid Leukemia: A Prospective Single Centre Trial From China[NCT03173612] | | 132 participants (Anticipated) | Interventional | 2016-08-31 | Recruiting |
| A Randomized Phase II Study of Nuclear Factor-kappa B (NF-κB) Inhibition During Induction Chemotherapy for Patients With Acute Myelogenous Leukemia[NCT02144675] | Phase 2 | 27 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Randomized Phase II Study Comparing Inotuzumab Plus Chemotherapy Versus Standard Chemotherapy in Older Adults With Philadelphia-Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia[NCT05303792] | Phase 2 | 66 participants (Anticipated) | Interventional | 2023-02-27 | Recruiting |
| Parent-Administered Low-Dose Cytarabine to Children and Adolescents With Cancer at Home - a Feasibility Study[NCT05372536] | | 15 participants (Anticipated) | Interventional | 2022-03-11 | Recruiting |
| Augmented Berlin-Frankfurt-Munster Therapy for Adolescents/Young Adults With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma[NCT00866749] | Phase 2 | 120 participants (Actual) | Interventional | 2006-09-12 | Completed |
| A PHASE IIA, MULTICENTER, OPEN-LABEL STUDY DESIGNED TO EVALUATE THE SAFETY AND EFFICACY OF ESCALATING DOSES OF BL-8040 IN ADULT SUBJECTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA[NCT01838395] | Phase 2 | 42 participants (Actual) | Interventional | 2013-04-30 | Completed |
| "A Feasibility Study of Early Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory High-Grade Myeloid Neoplasms"[NCT02756572] | Phase 2 | 30 participants (Actual) | Interventional | 2016-09-22 | Completed |
| Phase I Dose Finding/Phase II Placebo-Controlled Trial of Eltrombopag During Consolidation Therapy in Adults With Acute Myeloid Leukemia (AML) in Complete Remission[NCT01656252] | Phase 1/Phase 2 | 15 participants (Actual) | Interventional | 2012-07-31 | Terminated(stopped due to Study stopped per Novartis request due to futility from another study.) |
| A Two-Part Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib With CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia[NCT05627232] | Phase 1 | 24 participants (Anticipated) | Interventional | 2023-08-28 | Recruiting |
| A Phase II Study Using a BFM Regimen Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[NCT04845035] | Phase 2 | 23 participants (Anticipated) | Interventional | 2024-01-31 | Recruiting |
| A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL[NCT03150693] | Phase 3 | 310 participants (Anticipated) | Interventional | 2017-06-01 | Suspended(stopped due to Unacceptable Toxicity) |
| Randomized Phase II Trial of Timed Sequential Cytosine Arabinoside (Ara-C) With and Without the Checkpoint Kinase 1 (CHK1) Inhibitor MK-8776 in Adults With Relapsed AML[NCT01870596] | Phase 2 | 32 participants (Actual) | Interventional | 2013-05-31 | Completed |
| An Multicenter, Randomized, Controlled, Prospective Clinical Study of Mitoxantrone Liposome Combined With PTCy as Conditioning Regimen in Allo-HSCT in Acute Leukemia[NCT05739630] | Phase 2/Phase 3 | 60 participants (Anticipated) | Interventional | 2023-01-01 | Recruiting |
| A Phase I/II Trial of Venetoclax and BEAM Conditioning Followed by Autologous Stem Cell Transplantation for Patients With Primary Refractory Non-Hodgkin Lymphoma[NCT03583424] | Phase 1/Phase 2 | 19 participants (Actual) | Interventional | 2018-09-10 | Active, not recruiting |
| A Phase II Study Incorporating Panobinostat, Bortezomib and Liposomal Vincristine Into Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma[NCT02518750] | Phase 2 | 3 participants (Actual) | Interventional | 2016-11-23 | Terminated(stopped due to Due to slow accrual) |
| Phase I and Clinical Pharmacokinetic De-Escalation Study of 2'-Deoxycitidine Administered as a Continuous Infusion in Conjunction With a Continuous Infusion of High-Dose ARA-C in Patients With Refractory Acute Myelogenous Leukemia[NCT00002818] | Phase 1 | 15 participants (Actual) | Interventional | 1995-02-28 | Completed |
| A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia[NCT06084819] | Phase 2 | 200 participants (Anticipated) | Interventional | 2023-08-01 | Recruiting |
| Phase Ib/II Study of the Combination of Low-Intensity Chemotherapy and Tagraxofusp in Patients With Acute Lymphoblastic Leukemia (ALL)[NCT05032183] | Phase 1/Phase 2 | 40 participants (Anticipated) | Interventional | 2022-02-17 | Recruiting |
| Risk-stratified Therapy for Primary and Secondary AML and MDS. A Randomized Study by AMLCG in Relation to Cytogenetically Defined Prognostic Factors (1) on the Role of High-dose AraC as Part of Double Induction, (2) on G-CSF Priming, and (3) on High-dose [NCT00266136] | Phase 3 | 3,500 participants (Actual) | Interventional | 1999-06-30 | Completed |
| A Phase II Open-Label Study of High-Dose Cytarabine and Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Refractory or Relapsed Acute Lymphoblastic Leukemia[NCT01656031] | Phase 2 | 39 participants (Actual) | Interventional | 2005-02-28 | Completed |
| An Open-Label Phase 1/2 Multi-Arm Study of DS-1594b as a Single-Agent and in Combination With Azacitidine and Venetoclax or Mini-HCVD for the Treatment of Patients With Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)[NCT04752163] | Phase 1/Phase 2 | 17 participants (Actual) | Interventional | 2021-03-25 | Completed |
| A Phase I/II Study of the Selective Inhibitor of Nuclear Export Selinexor (KPT-330) in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Leukemia or Myelodysplastic Syndrome[NCT02212561] | Phase 1 | 19 participants (Actual) | Interventional | 2014-08-31 | Completed |
| Immune Consolidation With Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) After Peripheral Blood Stem Cell Transplant for High Risk CD20+ Non-Hodgkin's Lymphomas[NCT00244946] | Phase 1 | 15 participants (Actual) | Interventional | 2004-03-31 | Completed |
| A Phase I Study of Lenalidomide Plus Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine for the Reinduction of Patients With Acute Myelogenous Leukemia[NCT01681537] | Phase 1 | 36 participants (Actual) | Interventional | 2012-09-30 | Completed |
| Multicenter, Prospective, Open-label, Single-arm, Phase I-II Clinical Trial to Analyze Induction Therapy With a Combination of Fludarabine, Idarubicin, Cytarabine, G-CSF and Plerixafor for the Treatment of Young Patients With Relapsed or Refractory AML[NCT01435343] | Phase 1/Phase 2 | 55 participants (Actual) | Interventional | 2012-07-31 | Completed |
| Dose Escalation Study of Clofarabine in Combination With Cytarabine (Ara-C) and G-CSF Priming for Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients[NCT00602225] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2007-12-31 | Completed |
| A Phase Ib/II Multicenter Open-label Study of BGB324 as a Single Agent and in Combination With Cytarabine or Decitabine in Patients With Acute Myeloid Leukemia or as a Single Agent in Patients With Myelodysplastic Syndrome[NCT02488408] | Phase 1/Phase 2 | 121 participants (Actual) | Interventional | 2014-09-30 | Active, not recruiting |
| A Phase I Pharmacokinetic, Pharmacodynamic and Feasibility Study of Crenolanib in Combination With Sorafenib in Patients With Refractory or Relapsed Hematologic Malignancies (ARO-008)[NCT02270788] | Phase 1 | 10 participants (Actual) | Interventional | 2015-04-02 | Completed |
| A Phase I Trial of Imatinib Mesylate (Gleevec, Formerly Known as STI571) in Combination With Daunorubicin and Cytarabine for C-kit Positive Relapsed AML[NCT00268229] | Phase 1 | 21 participants (Actual) | Interventional | 2003-07-31 | Completed |
| Phase 1/2 Study of Cord Blood Transplantation From Unrelated Donor for Adult Patients With Hematologic Malignancies Using Myeloablative Conditioning Regimen[NCT00270881] | Phase 1/Phase 2 | 33 participants (Actual) | Interventional | 2006-01-31 | Completed |
| Phase 2 Open-Label Study of Amonafide L-Malate in Combination With Cytarabine in Subjects With Secondary Acute Myeloid Leukemia (AML)[NCT00273884] | Phase 2 | 80 participants | Interventional | 2005-08-31 | Completed |
| Phase II Study of Induction Therapy Comprising Etoposide, Methylprednisolone, Cytarabine, and Cisplatin (ESHAP) Followed by Consolidation Therapy Comprising Rituximab and Yttrium Y 90 Ibritumomab Tiuxetan in Patients With Relapsed or Refractory AIDS-Relat[NCT00310128] | Phase 2 | 0 participants (Actual) | Interventional | 2006-02-28 | Withdrawn(stopped due to Drug supply unavailable) |
| Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: A Pilot Study[NCT00416819] | | 10 participants (Actual) | Interventional | 2003-09-30 | Completed |
| AML Therapy With Irradiated Allogeneic Cells[NCT02105116] | | 6 participants (Actual) | Interventional | 2014-02-28 | Terminated(stopped due to No patients were eligible to receive the experimental component of the protocol therapy.) |
| Phase 1 Study of Venetoclax/Azacitidine or Venetoclax in Combination With Ziftomenib or Standard Induction Cytarabine/Daunorubicin (7+3) Chemotherapy in Combination With Ziftomenib for the Treatment of Patients With Acute Myeloid Leukemia[NCT05735184] | Phase 1 | 212 participants (Anticipated) | Interventional | 2023-07-18 | Recruiting |
| A Phase Ib Trial With Dose Expansion Evaluating CPX-351 Plus Gemtuzumab Ozogamicin for Relapsed Acute Myelogenous Leukemia[NCT03904251] | Phase 1 | 13 participants (Actual) | Interventional | 2019-07-18 | Terminated(stopped due to slow accrual) |
| A Phase I Study of Lintuzumab-Ac225 in Combination With CLAG-M Chemotherapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia[NCT03441048] | Phase 1 | 26 participants (Actual) | Interventional | 2018-05-22 | Active, not recruiting |
| A Phase 3, Double-Blind, Placebo-controlled Study of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy, and Administered as Continuation Therapy in Subjects 18 to 75 Years Old With Newly Diagnosed FLT3-ITD (+) Acute Mye[NCT02668653] | Phase 3 | 539 participants (Actual) | Interventional | 2016-09-01 | Completed |
| A Phase I Open-Label Study of High-Dose Cytarabine and Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Refractory or Relapsed Acute Lymphoblastic Leukemia[NCT00295841] | Phase 1 | 53 participants (Actual) | Interventional | 2005-02-28 | Completed |
| Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients[NCT01876953] | Phase 1/Phase 2 | 20 participants (Actual) | Interventional | 2013-09-13 | Terminated(stopped due to Due to the budget issues, the study discontinued at Phase II.) |
| Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With SCH54031 (PEG Interferon Alpha 2B/PEG Intron) and Low-Dose Cytosine Arabinoside (Ara-C)[NCT00303290] | Phase 1 | 76 participants (Actual) | Interventional | 2000-01-31 | Completed |
| Randomized Phase III Study Comparing the OSHO Arm to the Standard Intergroup Arm.[NCT01497002] | Phase 3 | 1,222 participants (Actual) | Interventional | 2005-04-30 | Completed |
| A Phase II Study Of Pooled Unrelated Donor Umbilical Cord Blood (UCB) Transplant For Patients With Hematologic Malignancies Needing Allogeneic Stem Cell Transplant But Do Not Have A Related HLA-Matched Donor[NCT01500161] | Phase 2 | 1 participants (Actual) | Interventional | 2011-11-30 | Terminated(stopped due to Insufficient accruals) |
| A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma[NCT01511562] | Phase 2 | 113 participants (Actual) | Interventional | 2012-09-30 | Active, not recruiting |
| Randomized Phase II Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)[NCT01627041] | Phase 2 | 178 participants (Actual) | Interventional | 2011-09-16 | Active, not recruiting |
| A Multicenter, Open Label, Phase 1B Study of Escalating Doses of RO5045337 Administered Orally, With Cytarabine Administered A) Subcutaneously, or B) Intravenously, in Patients With Acute Myelogenous Leukemia (AML)[NCT01635296] | Phase 1 | 43 participants (Actual) | Interventional | 2012-07-31 | Completed |
| Phase I/II Study of Cytarabine or 5-Azacitidine Combined With Tosedostat to Evaluate the Safety and Tolerability in Older Patients With Acute Myeloid Leukemia (AML) or High Risk MDS[NCT01636609] | Phase 1 | 18 participants (Actual) | Interventional | 2012-11-20 | Terminated(stopped due to In 2013 the FDA put a temporary hold on the trial and the Phase II portion of this study was cancelled.) |
| Phase II Trial Examining Epigenetic Priming With Decitabine Followed by Idarubicin and Cytarabine for Patients With Relapsed or Refractory AML.[NCT01607645] | Phase 2 | 7 participants (Actual) | Interventional | 2012-07-31 | Terminated(stopped due to The study was terminated early because there were other competing protocols.) |
| Efficacy and Safety of Chidamide in CBF Leukemia[NCT03031262] | Phase 1/Phase 2 | 250 participants (Anticipated) | Interventional | 2017-02-08 | Recruiting |
| Role of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Patients Wih Leptomeningeal Metastasis of Breast Cancer. A Randomized Phase III Study.[NCT01645839] | Phase 3 | 74 participants (Actual) | Interventional | 2011-08-30 | Completed |
| A Randomised Study of High Dose Chemotherapy/Radiotherapy and Autologous Bone Marrow Transplantation in Patients With High Grade Malignant Non-Hodgkin's Lymphoma (Kiel Classification) According to Prognostic Groups[NCT00003815] | Phase 3 | 0 participants | Interventional | 1994-06-30 | Active, not recruiting |
| A Phase II Trial to Evaluate the Safety, Feasibility and Efficacy of a Salvage Therapy Consisting of Temsirolimus Added to the Standard Therapy R-DHAP for the Treatment of Patients With Relapsed or Refractory DLBCL - the STORM Trial[NCT01653067] | Phase 2 | 88 participants (Anticipated) | Interventional | 2012-09-30 | Active, not recruiting |
| Phase II Trial Utilizing Idarubicin in Combination With High Dose Ara-C for Induction Therapy for Adult Acute Myelogenous Leukemia (AML)[NCT00528398] | Phase 2 | 111 participants (Actual) | Interventional | 1994-09-30 | Completed |
| A Phase I Study of Venetoclax to Augment Epigenetic Modification and Chemotherapy in Pediatric and Young Adult Patients With Relapsed and Refractory Acute Myeloid Leukemia[NCT05317403] | Phase 1 | 40 participants (Anticipated) | Interventional | 2023-03-31 | Recruiting |
| Phase 1/2 Study of Decitabine Combined With Modified CAG Followed by HLA Haploidentical T Cell Infusion in Treating Elderly Patients With Intermediate-high Risk Myelodysplastic Syndrome(MDS) or Acute Myeloid Leukemia(AML）[NCT01690507] | Phase 1/Phase 2 | 29 participants (Actual) | Interventional | 2012-11-30 | Completed |
| A Pilot Study of CPX-351 (Vyxeos™) for Transplant Eligible, Higher Risk Patients With Myelodysplastic Syndrome[NCT03572764] | Phase 1 | 20 participants (Actual) | Interventional | 2018-12-14 | Active, not recruiting |
| A Phase II Study of Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma[NCT01700946] | Phase 2 | 80 participants (Actual) | Interventional | 2013-04-15 | Completed |
| A Randomized, Blinded, Placebo-Controlled, Dose Finding Study to Assess the Safety and Efficacy of the Oral Thrombopoietin Receptor Agonist, Eltrombopag, Administered to Subjects With Acute Myelogenous Leukaemia (AML) Receiving Induction Chemotherapy[NCT01890746] | Phase 2 | 148 participants (Actual) | Interventional | 2013-09-05 | Completed |
| Treatment Protocol for Newky Diagnosed Adult Ph-Chromosome Positive (BCR::ABL1) Acute Lymphoblastic Leukemia (LALPh2022)[NCT06175702] | | 150 participants (Anticipated) | Observational | 2023-12-25 | Not yet recruiting |
| Consolidation With ADCT-402 (Loncastuximab Tesirine) After a Short Course of Immunochemotherapy: a Phase II Study in BTKi-treated (or BTKi Intolerant) Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Patients[NCT05249959] | Phase 2 | 56 participants (Anticipated) | Interventional | 2022-04-21 | Recruiting |
| CD19-specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies[NCT00968760] | Phase 1 | 34 participants (Actual) | Interventional | 2011-06-20 | Completed |
| A Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Lymphodepleting Chemotherapy and Lenalidomide as Immunotherapy in Patients With Hematologic Malignancies[NCT02280525] | Phase 1 | 8 participants (Actual) | Interventional | 2015-03-05 | Completed |
| A Phase II Study of Yttrium-90-Labeled Anti-CD20 Monoclonal Antibody in Combination With High-Dose Beam Followed by Autologous Stem Cell Transplantation for Poor Risk/Relapsed B-Cell Lymphoma[NCT00695409] | Phase 2 | 122 participants (Actual) | Interventional | 2008-03-18 | Completed |
| An Open Label, Dose-Escalation Study to Evaluate Safety, Tolerability, Maximum Tolerated Dose (MTD), Efficacy, and Pharmacokinetics (PKs) of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leu[NCT01768897] | Phase 1 | 67 participants (Actual) | Interventional | 2013-01-31 | Completed |
| AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA[NCT01769911] | | 0 participants (Actual) | Interventional | 2015-02-28 | Withdrawn |
| Safety and Efficacy of Implementing Low-Dose Coronary Computed Tomographic Angiography for Early Triage of Acute Chest Pain in Emergency Department[NCT01770444] | | 681 participants (Actual) | Interventional | 2012-12-31 | Completed |
| A Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With Acute Myeloid Leukemia[NCT01779843] | Phase 1 | 22 participants (Actual) | Interventional | 2013-04-30 | Completed |
| An Open-Label, Single-Dose Study Designed to Assess the Mass Balance Recovery of an Intravenous Microdose of [14C]-Elacytarabine in Healthy Male Subjects[NCT01783964] | Phase 1 | 6 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Phase I/II Clinical Trial Testing the Safety and Feasibility of IL-21-Expanded Natural Killer Cells for the Induction of Relapsed/Refractory Acute Myeloid Leukemia[NCT01787474] | Phase 1 | 30 participants (Actual) | Interventional | 2014-05-19 | Completed |
| Phase III Randomized Study of Crenolanib Versus Midostaurin Administered Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed Subjects With FLT3 Mutated Acute Myeloid Leukemia[NCT03258931] | Phase 3 | 510 participants (Anticipated) | Interventional | 2018-08-15 | Recruiting |
| A Phase II Study of Intrathecal and Systemic Chemotherapy With Radiation Therapy for Children With Central Nervous System Atypical Teratoid/Rhabdoid Tumor (AT/RT) Tumor[NCT00084838] | Phase 2 | 25 participants (Actual) | Interventional | 2003-02-28 | Completed |
| A Phase II Study of Sulindac, a COX Inhibitor, in Older Patients With Acute Myeloid Leukemia in First Complete Remission[NCT01843179] | Phase 2 | 0 participants (Actual) | Interventional | 2014-01-31 | Withdrawn(stopped due to Lack of Funding) |
| Phase 1 Trial of Ivosidenib and FLAG Chemotherapy in Relapsed/Refractory IDH1+ Acute Myeloid Leukemia (AML)[NCT04250051] | Phase 1 | 25 participants (Anticipated) | Interventional | 2020-12-21 | Recruiting |
| Treatment of Poor Prognosis Acute Myeloid Leukemia and Blastic Crisis Chronic Myelogenous Leukemia With Mylotarg, High-Dose Cytarabine, Mitozantrone and Ethyol AML/CML 2000-06.[NCT00003407] | Phase 2 | 0 participants (Actual) | Interventional | 2001-02-13 | Withdrawn(stopped due to The P.I deceased.) |
| "Randomized Phase II Trial of Timed Sequential Therapy (TST) With Alvocidib (Flavopiridol), Ara-C and Mitoxantrone (FLAM) vs. 7+3 for Adults Age 70 and Under With Newly Diagnosed Acute Myelogenous Leukemia (AML)"[NCT01349972] | Phase 2 | 172 participants (Actual) | Interventional | 2011-04-30 | Completed |
| Phase 2 Study of Rituximab and ESHAP (Etoposide, Methylprednisolone, Cytarabine, and Cisplatin) in Relapsed and Refractory Aggressive Non-Hodgkin's Lymphoma[NCT00367497] | Phase 2 | 5 participants (Actual) | Interventional | 2005-08-31 | Terminated(stopped due to The stopping rule was applied because of low response rates.) |
| A Phase I Trial of Pevonedistat in Combination With Induction Chemotherapy for Adolescent and Young Adults With Relapsed/Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Non-Hodgkin Lymphoma[NCT03349281] | Phase 1 | 6 participants (Actual) | Interventional | 2019-03-25 | Completed |
| Phase 1/2 Study of Concurrent Decitabine in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)[NCT02921061] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2016-11-17 | Completed |
| Safety and Efficiency of Anti-CD19/CD22 Tandem Fully Human Chimeric Antigen Receptor (CAR)-Transduced T-cell Therapy for Pediatric and Young Adult Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia: a Single Centre, Non-randomised, Open[NCT04499573] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2020-07-27 | Active, not recruiting |
| Phase I Study of Vorinostat (Suberoylanilide Hydroxamic Acid, or SAHA) in Combination With Cytosine Arabinoside (Ara-C) and Etoposide for Patients With Relapsed and/or Refractory Acute Leukemias, Myelodysplasias and Myeloproliferative Disorders[NCT00357305] | Phase 1 | 25 participants (Actual) | Interventional | 2006-05-31 | Completed |
| A PHASE 1B/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-04449913, AN ORAL HEDGEHOG INHIBITOR, IN COMBINATION WITH INTENSIVE CHEMOTHERAPY, LOW DOSE ARA-C OR DECITABINE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME[NCT01546038] | Phase 2 | 255 participants (Actual) | Interventional | 2012-06-27 | Completed |
| Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma[NCT00000801] | Phase 2 | 33 participants | Interventional | | Completed |
| Phase II Study of Venetoclax Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Cladribine Plus LDAC Alternating With 5-Azacitidine With Venetoclax in Patients With Untreated AML[NCT03586609] | Phase 2 | 145 participants (Anticipated) | Interventional | 2018-10-25 | Recruiting |
| Phase II Study of High-Dose Cytarabine, Cisplatin, and Dexamethasone Followed By Cyclophosphamide, Etoposide, Total Body Irradiation, and Autologous Bone Marrow Rescue in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma[NCT00002481] | Phase 2 | 0 participants | Interventional | 1990-03-31 | Active, not recruiting |
| TREATMENT OF ALL IN FIRST BONE MARROW RELAPSE AFTER BFM PROTOCOLS[NCT00002499] | Phase 2/Phase 3 | 0 participants | Interventional | 1990-01-31 | Active, not recruiting |
| IDA VS MTZ IN INDUCTION AND INTENSIFICATION TREATMENT OF AML OR MDS IN CHILDREN, A PHASE III RANDOMIZED STUDY[NCT00002517] | Phase 3 | 0 participants | Interventional | 1993-03-31 | Completed |
| ALLOGENEIC AND SYNGENEIC MARROW TRANSPLANTATION IN PATIENTS WITH ACUTE NON-LYMPHOCYTIC LEUKEMIA[NCT00002547] | Phase 2 | 280 participants (Actual) | Interventional | 1987-08-31 | Completed |
| A Phase I and Expansion Cohort Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia[NCT04898894] | Phase 1 | 42 participants (Anticipated) | Interventional | 2021-11-15 | Recruiting |
| "RANDOMIZED COMPARISON OF ALTERNATING TRIPLE THERAPY (ATT) VERUS CHOP IN PATIENTS WITH INTERMEDIATE GRADE LYMPHOMAS AND IMMUNOBLASTIC LYMPHOMAS WITH INTERNATIONAL INDEX 2-5"[NCT00002565] | Phase 3 | 61 participants (Actual) | Interventional | 1994-05-25 | Completed |
| Study of Promace-Cytabom With Trimethoprim Sulfamethoxazole, Zidovudine (AZT), and Granulocyte Colony Stimulating Factor (G-CSF) in Patients With AIDS-Related Lymphoma, Phase II[NCT00002571] | Phase 2 | 52 participants (Actual) | Interventional | 1994-06-30 | Completed |
| International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Sub-protocol B Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric P[NCT05751044] | Phase 1/Phase 2 | 26 participants (Anticipated) | Interventional | 2023-10-01 | Not yet recruiting |
| FAB LMB 96 -- Treatment of Mature B-CELL Lymphoma/Leukemia: A SFOP LMB 96/CCG 5961/UKCCSG NHL 9600 Cooperative Study[NCT00002757] | Phase 3 | 1,148 participants (Actual) | Interventional | 2001-06-30 | Completed |
| T-Cell Replete Haploidentical Donor Hematopoietic Stem Cell Plus Natural Killer (NK) Cell Transplantation in Patients With Hematologic Malignancies Relapsed or Refractory Despite Previous Allogeneic Transplant[NCT01621477] | Phase 2 | 34 participants (Actual) | Interventional | 2012-08-31 | Terminated(stopped due to Study was terminated in August 2016 due to replacement by a new study.) |
| Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients With Leptomeningeal Metastases With or Without Parenchymal Brain Involvement[NCT00992602] | Phase 2 | 3 participants (Actual) | Interventional | 2011-04-30 | Completed |
| A Phase 2 Trial of Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Combined With BEAM Chemotherapy (aTac-BEAM) Conditioning for Autologous Hematopoietic Cell Transplantation (AHCT) in Patients With Primary Refractory or Relapsed Hodgkin Lymphoma[NCT04871607] | Phase 2 | 33 participants (Anticipated) | Interventional | 2021-11-02 | Recruiting |
| Efficacy and Safety of Rituximab, High-dose Ara-C and Dexamethasone (R-HAD) Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma[NCT01449344] | Phase 3 | 128 participants (Actual) | Interventional | 2009-05-09 | Active, not recruiting |
| Sequential Chemotherapy and Lenalidomide Followed by Rituximab and Lenalidomide Maintenance for Untreated Mantle Cell Lymphoma: A Phase II Study[NCT02633137] | Phase 2 | 49 participants (Actual) | Interventional | 2015-12-14 | Completed |
| RAVEN: A Phase I/II Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax[NCT05192889] | Phase 1/Phase 2 | 90 participants (Anticipated) | Interventional | 2022-08-25 | Recruiting |
| High-Dose Immunosuppressive Therapy Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) + Thymoglobulin Followed by Syngeneic or Autologous Hematopoietic Cell Transplantation for Patients With Autoimmune Neurologic Diseases[NCT00716066] | Phase 2 | 80 participants (Anticipated) | Interventional | 2008-06-30 | Recruiting |
| A Phase I Trial of Temsirolimus (CCI-779, Pfizer, Inc.) in Combination With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma[NCT01614197] | Phase 1 | 16 participants (Actual) | Interventional | 2015-07-03 | Completed |
| A Phase I Dose Finding and Proof-of-concept Study of the Histone Deacetylase Inhibitor Panobinostat (LBH589) in Combination With Standard Dose Cytarabine and Daunorubicin for Older Patients With Untreated Acute Myeloid Leukemia or Advanced Myelodysplastic[NCT01463046] | Phase 1 | 29 participants (Actual) | Interventional | 2012-01-31 | Completed |
| A Prospective, Multicenter, Single-Arm Pilot Study of CPX-351 (VYXEOS) in Individuals < 22 Years With Secondary Myeloid Neoplasms[NCT05656248] | Phase 2 | 25 participants (Anticipated) | Interventional | 2023-01-17 | Recruiting |
| A Phase 1/1b Dose Escalation and Expansion of CPX-351 in Combination With Gemtuzumab Ozogamicin in Newly Diagnosed Acute Myeloid Leukemia[NCT05558124] | Phase 1 | 18 participants (Anticipated) | Interventional | 2022-09-22 | Recruiting |
| Phase I/II Trial Of Sequential Therapy With Cytarabine And Bismuth-213-Labeled HuM195 (Humanized Anti-CD33) In Patients With Advanced Myeloid Malignancies[NCT00014495] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2000-11-30 | Completed |
| A Pilot Study of Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma[NCT03623373] | Phase 2 | 13 participants (Actual) | Interventional | 2018-11-29 | Active, not recruiting |
| A Phase II Randomized Trial of Carboplatin and Topotecan; Flavopiridol, Mitoxantrone and Cytosine Arabinoside; and Sirolimus, Mitoxantrone, Etoposide and Cytosine Arabinoside for the Treatment of Adults With Primary Refractory or Initial Relapse of Acute [NCT00634244] | Phase 2 | 92 participants (Actual) | Interventional | 2008-10-31 | Completed |
| T2007-002 A Phase II Study of Clofarabine With Etoposide and Cyclophosphamide in Relapsed/Refractory AML (IND 104,650)[NCT00939653] | Phase 2 | 6 participants (Actual) | Interventional | 2009-07-10 | Terminated(stopped due to Due to insufficient research institution participation and patient enrollment) |
| Treateament of Newly Diagnosed Acute Monocytic Leukemia in Children： A Prospective Multicenter Study in South China[NCT05313958] | Phase 2/Phase 3 | 43 participants (Anticipated) | Interventional | 2021-12-01 | Recruiting |
| Clinical Study on the Safety and Efficacy of QN-030a in Acute Myeloid Leukemia With Minimal Residual Disease[NCT05601830] | Phase 1 | 18 participants (Anticipated) | Interventional | 2022-10-28 | Recruiting |
| A Prospective Clinical Study of Hanlikang and BTK Inhibitors in the Treatment of Newly Diagnosed Mantle Cell Lymphoma[NCT05506410] | | 100 participants (Anticipated) | Observational [Patient Registry] | 2022-08-12 | Recruiting |
| Clinical Study of Bcl-2 Inhibitors Combined With Azacytidine and Chemotherapy in Elderly Patients With Previously Untreated Acute Myeloid Leukemia[NCT05053425] | | 30 participants (Anticipated) | Interventional | 2021-10-20 | Recruiting |
| An Investigator Sponsored Phase I/II Study of CLAG + Selinexor in Relapsed or Refractory Acute Myeloid Leukemia[NCT02416908] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2015-06-16 | Completed |
| Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Anemia From HLA Matched or Partially-Matched Related Donors[NCT01350232] | | 2 participants (Actual) | Interventional | 2009-09-30 | Terminated(stopped due to Poor accrual) |
| A Randomized Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA and Idarubicin Versus Standard ATRA and Anthracyclines-based Chemotherapy (AIDA Regimen) for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia[NCT02688140] | Phase 3 | 280 participants (Anticipated) | Interventional | 2016-06-30 | Active, not recruiting |
| A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin's Lymphoma[NCT00000658] | Phase 3 | 250 participants | Interventional | | Completed |
| HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR DIFFUSE SMALL NONCLEAVED CELL LYMPHOMA AND THE L-3 SUBTYPE OF ALL: A PILOT STUDY OF A MULTIDRUG REGIMEN[NCT00002494] | Phase 2 | 134 participants (Actual) | Interventional | 1992-05-31 | Completed |
| Multicenter Study to Optimise Therapy of B-ALL, Burkitt's NHL and High-Grade Non-Hodgkin's Lymphoma in Adults (Amend 7)[NCT00199082] | Phase 4 | 650 participants (Anticipated) | Interventional | 2002-07-31 | Completed |
| HIGH-DOSE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR CHILDREN WITH RELAPSED ACUTE LYMPHOCYTIC LEUKEMIA[NCT00002638] | Phase 2 | 30 participants (Anticipated) | Interventional | 1995-03-31 | Completed |
| CYTOREDUCTIVE CHEMOTHERAPY WITH MITOXANTRONE, CYTOSINE ARABINOSIDE AND ETOPOSIDE FOLLOWED BY RECOMBINANT HUMAN G-CSF FOR MOBILIZATION OF PERIPHERAL BLOOD STEM CELLS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA[NCT00002674] | Phase 2 | 30 participants (Anticipated) | Interventional | 1994-10-31 | Completed |
| TREATMENT OF ISOLATED CNS RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA -- A PEDIATRIC ONCOLOGY GROUP-WIDE PHASE II STUDY[NCT00002704] | Phase 2 | 156 participants (Actual) | Interventional | 1996-01-31 | Completed |
| A Pilot Study For The Treatment of Newly-Diagnosed Disseminated Anaplastic Large Cell Ki-1 Lymphoma and T-Large Cell Lymphoma[NCT00002590] | Phase 2 | 221 participants (Actual) | Interventional | 1994-07-31 | Completed |
| Phase II Study of Age-Adjusted R-BAC (Rituximab, Bendamustine, Cytarabine) as Induction Therapy in Older Patients With Mantle Cell Lymphoma (MCL)[NCT01662050] | Phase 2 | 57 participants (Actual) | Interventional | 2012-03-20 | Completed |
| Autologous Peripheral Blood Stem Cell Transplantation (PSCT) Versus a Second Intensive Consolidation Course After a Common Induction and Consolidation Course in Patients With Bad Prognosis Myelodysplastic Syndromes (MDS) and Acute Myelogenous Leukemia Sec[NCT00002926] | Phase 3 | 80 participants (Anticipated) | Interventional | 1996-12-31 | Active, not recruiting |
| A Phase lb Study of the Safety, Feasibility, and Pharmacokinetics of AMG 386 Alone and in Combination With Low Dose Cytarabine in Acute Myeloid Leukemia (AML) Patients[NCT01555268] | Phase 1 | 24 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Medical Research Council Working Party on Leukaemia in Childhood Acute Myeloid Leukaemia Trial 12[NCT00003436] | Phase 3 | 2,000 participants (Anticipated) | Interventional | 1998-07-31 | Completed |
| PHASE II STUDY OF HIGH DOSE CYTARABINE COMBINED WITH A SINGLE HIGH DOSE OF IDARUBICIN FOR NEWLY DIAGNOSED PATIENTS WITH AML: THE AML-3 PROTOCOL[NCT00002800] | Phase 2 | 60 participants (Anticipated) | Interventional | 1996-07-31 | Completed |
| Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features: A Phase III Group-wide Study[NCT00002812] | Phase 3 | 2,078 participants (Actual) | Interventional | 1996-09-30 | Completed |
| Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With rIL-2 (NSC #373364) vs. No Further Therapy in Previously Untreated Patients With AML >60 Years[NCT00003190] | Phase 3 | 640 participants (Actual) | Interventional | 1998-01-31 | Completed |
| Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy With or Without Arsenic Trioxide (AS2O3) (NSC # 706363) as Initial Consolidation Therapy Followed by Maintenance Therapy With Intermittent Tretinoin Versus Intermittent Tretinoin Plus Mer[NCT00003934] | Phase 3 | 420 participants (Actual) | Interventional | 1999-06-30 | Completed |
| A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine[NCT00003694] | Phase 2 | 60 participants (Actual) | Interventional | 1999-03-31 | Completed |
| Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia Testing Increased Doses of Daunorubicin During Induction, and Cytarabine During Consolidation, Followed by High-Dose Methotrexate and Intrathecal Methotrexate in Place of Cranial Irradia[NCT00003700] | Phase 2 | 163 participants (Actual) | Interventional | 1999-01-31 | Completed |
| A Phase I Study of Cytosine Arabinoside, Idarubicin, and Amifostine as Induction Therapy for Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT00003268] | Phase 1 | 0 participants | Interventional | 1998-01-31 | Completed |
| PHASE I-II STUDY OF IDARUBICIN, CYTARABINE AND R115777 (TIPIFARNIB, ZARNESTRA; 702818; IND 58359), A FARNESYLTRANSFERASE INHIBITOR, IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIAS[NCT00096122] | Phase 1/Phase 2 | 95 participants (Actual) | Interventional | 2004-09-30 | Completed |
| Non-Myeloablative Chemotherapy Followed by Unrelated Allogeneic Stem Cell Transplantation in Patients With Advanced Hematologic Malignancies: A Pilot Study[NCT00004114] | Phase 1 | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to Study never opened) |
| Phase I/II Study of the Combination of Low-Intensity Chemotherapy and Venetoclax (ABT-199) in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)[NCT03808610] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2019-04-03 | Recruiting |
| A Phase 2 Trial to Evaluate the Efficacy of Bortezomib, Cytarabine, and Dexamethasone in Patients With Relapsed or Refractory Mantle Cell Lymphoma[NCT02840539] | Phase 2 | 19 participants (Actual) | Interventional | 2016-10-11 | Completed |
| Clinical Study on QN-023a Targeting CD33 in Relapsed/Refractory Acute Myeloid Leukemia[NCT05601466] | Phase 1 | 18 participants (Anticipated) | Interventional | 2022-10-28 | Recruiting |
| Phase I Study of Yttrium-90 Labeled Anti-CD25 Monoclonal Antibody Plus Standard BEAM Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Mature T-Cell Non-Hodgkin Lymphoma: the aTAC BEAM Regimen[NCT02342782] | Phase 1 | 20 participants (Actual) | Interventional | 2020-06-08 | Active, not recruiting |
| Pilot Study for Treatment of Elderly Patients (>65 Years) With Acute Lymphoblastic Leukemia[NCT00199095] | Phase 4 | 40 participants | Interventional | 1997-02-28 | Completed |
| Multicenter Study To Optimize Treatment in Elderly Patients (> 55 Years, No Upper Age Limit) With Acute Lymphoblastic Leukemia (GMALL Elderly 1/2003)(Amend 2)[NCT00198978] | Phase 4 | 377 participants (Actual) | Interventional | 2003-01-31 | Completed |
| A Biomarker Validation Study to Establish Whether Serial Flow Cytometric Measurements Predict Clinical Response to Sirolimus and MEC (Mitoxantrone Etoposide Cytarabine) Treatment in Patients With High-Risk Acute Myelogenous Leukemia[NCT02583893] | Phase 2 | 39 participants (Actual) | Interventional | 2015-10-07 | Completed |
| A Phase II Study To Determine The Anti-Leukemic Effects Of STI571 In Combination With Ara-C In Patients With Chronic Myelogenous Leukemia In Chronic Phase[NCT00022490] | Phase 2 | 24 participants (Actual) | Interventional | 2001-06-30 | Terminated |
| ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study[NCT00005596] | Phase 3 | 1,076 participants (Actual) | Interventional | 2000-04-30 | Completed |
| Reduced Burden of Oncologic Therapy in Advanced B-cell Lymphoma (REBOOT ABLY) in Children, Adolescents and Young Adults With CD20+ Mature B-Cell Lymphoma[NCT01859819] | Phase 2 | 45 participants (Actual) | Interventional | 2013-01-31 | Completed |
| An International Randomised Clinical Trial of Therapeutic Interventions to Assess the Effects on Outcome in Adults With Acute Myeloid Leukaemia and High Risk Myelodysplasia Undergoing Allogeneic Stem Cell Transplantation.[NCT04217278] | Phase 2/Phase 3 | 333 participants (Actual) | Interventional | 2020-01-27 | Active, not recruiting |
| A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®) During Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With Ge[NCT00085709] | Phase 3 | 637 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Clofarabine With Cytarabine for MRD Positive Leukemia[NCT01158885] | Phase 2 | 2 participants (Actual) | Interventional | 2010-08-31 | Terminated(stopped due to Study terminated for lack of accrual.) |
| An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Efficacy and Pharmacokinetics of BI 811283 in Combination With Cytarabine in Patients With Previously Untreated Acute Myeloid Leukaemia Ineligible for Intensive Treatment[NCT00632749] | Phase 2 | 68 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Phase I/II Randomized Study of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI) in Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome[NCT01289457] | Phase 1/Phase 2 | 282 participants (Actual) | Interventional | 2011-02-02 | Completed |
| Reducing the Burden of Oncologic Chemoradiotherapy And Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Lymphoma[NCT05253495] | Phase 2 | 80 participants (Anticipated) | Interventional | 2022-02-01 | Recruiting |
| Phase I Dose Escalation Study of Millennium 9708 in Combination With Induction and Consolidation Chemotherapy in Adults >= 60 Years With Acute Myeloid Leukemia[NCT02582359] | Phase 1 | 39 participants (Actual) | Interventional | 2016-01-31 | Completed |
| Evaluation of Functional Rehabilitation Fast Track Total Hip Arthroplasty vs Standard Care: a Randomized Controlled Trial[NCT04211987] | | 93 participants (Actual) | Interventional | 2018-03-13 | Completed |
| Phase 1 Study of Selinexor in Combination With Topoisomerase-II Inhibition in Acute Myeloid Leukemia[NCT02299518] | Phase 1 | 23 participants (Actual) | Interventional | 2015-05-18 | Completed |
| Cytarabine Monotherapy for Adult Patients With Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study[NCT04121819] | Phase 2 | 40 participants (Anticipated) | Interventional | 2019-10-01 | Recruiting |
| German Multicenter Study for Treatment Optimisation in Acute Lymphoblastic Leukemia in Adults and Adolescents Above 15 Years (Amend 3) (GMALL 07/2003)[NCT00198991] | Phase 4 | 1,883 participants (Actual) | Interventional | 2003-04-30 | Completed |
| Open-label, Multicenter Phase I/II Study: Salvage Therapy of Progressive and Relapsed Aggressive Non-Hodgkin-Lymphoma by Combination of Lenalidomide (Revlimid®) With Rituximab, Dexamethason, High-dose ARA-C and Cisplatinum (R²-DHAP)[NCT02983097] | Phase 1/Phase 2 | 34 participants (Actual) | Interventional | 2010-11-30 | Terminated(stopped due to Phase II: no scientific interests are given anymore) |
| Zevalin And Rituxan For The Treatment Of Relapsed Or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma[NCT00073957] | Phase 2 | 25 participants (Actual) | Interventional | 2003-12-31 | Completed |
| UARK 98-026, Total Therapy II - A Phase III Study for Newly Diagnosed Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy[NCT00083551] | Phase 3 | 668 participants (Actual) | Interventional | 1998-08-31 | Completed |
| ChiCGB Versus BEAM With Autologous Stem-Cell Transplantation in High-risk Hodgkin and Non-Hodgkin Lymphoma - A Prospective, Multi-centered, Randomized Clinical Trial[NCT05466318] | Phase 3 | 306 participants (Anticipated) | Interventional | 2022-07-01 | Recruiting |
| A Prospective Institutional Study for the Treatment of Children With Newly Diagnosed Langerhans Cell Histiocytosis Using a Cytarabine Contained Protocol[NCT04773366] | Phase 3 | 200 participants (Anticipated) | Interventional | 2018-07-01 | Recruiting |
| A Study of Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia[NCT00186875] | Phase 2 | 47 participants (Actual) | Interventional | 2003-11-30 | Completed |
| Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy[NCT01444742] | Phase 2 | 81 participants (Actual) | Interventional | 2011-11-16 | Completed |
| A Phase 2, Open-label, Randomized, Two-stage Clinical Study of Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia Following Treatment With Venetoclax Combination Therapy[NCT03969420] | Phase 2 | 11 participants (Actual) | Interventional | 2020-01-15 | Terminated(stopped due to Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021.) |
| A Phase 2 Study of E7070, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndromes[NCT01692197] | Phase 2 | 43 participants (Actual) | Interventional | 2013-02-01 | Completed |
| Pilot Study of Vosaroxin and Cytarabine for the Treatment of Adults 60 Years of Age or Older With Previously Untreated AML[NCT02485353] | | 2 participants (Actual) | Interventional | 2015-10-20 | Terminated(stopped due to Safety concerns) |
| A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)[NCT02343939] | Phase 1/Phase 2 | 148 participants (Actual) | Interventional | 2015-07-01 | Terminated |
| A Single-arm, Single-center Trial of Prophylactic Tocilizumab for Acute GVHD Prevention After Haploidentical HSCT.[NCT04688021] | Phase 2 | 46 participants (Anticipated) | Interventional | 2020-12-03 | Recruiting |
| Induction Therapy With Pacritinib Combined With Decitabine or Cytarabine in Older Patients With Acute Myeloid Leukemia (AML)[NCT02532010] | Phase 2 | 13 participants (Actual) | Interventional | 2015-06-15 | Terminated(stopped due to The study was put on clinical hold by the sponsor since Feb 9th 2016, and was later decided not to re-open due to financial constraints.) |
| Efficacy and Safety of ATO Plus ATRA in Nucleophosmin-1 Mutated Acute Myeloid Leukemia[NCT03031249] | Phase 1/Phase 2 | 80 participants (Anticipated) | Interventional | 2017-02-08 | Recruiting |
| A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)[NCT00882206] | Phase 2 | 15 participants (Actual) | Interventional | 2009-04-30 | Terminated(stopped due to Slow accrual) |
| A Phase III Randomised, Double-blind, Controlled, Parallel Group Study of Intravenous Volasertib in Combination With Subcutaneous Low-dose Cytarabine vs. Placebo + Low-dose Cytarabine in Patients >=65 Years With Previously Untreated Acute Myeloid Leukaemi[NCT01721876] | Phase 3 | 666 participants (Actual) | Interventional | 2013-01-29 | Completed |
| Phase II Evaluation of Gallium Nitrate (NSC 15200) in Non-Hodgkin's Lymphoma in Patients With Acquired Immunodeficiency Syndrome[NCT00002578] | Phase 2 | 35 participants (Anticipated) | Interventional | 1994-08-31 | Completed |
| Comparison of Ara-c 12 gm/m2 vs 18 gm/m2 Per Cycle for 3 Cycles Each as Consolidation in AML ; An Open Label Randomized Non-inferiority Study[NCT01615757] | Phase 3 | 180 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| A Phase II Study Incorporating Sorafenib (NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia[NCT01253070] | Phase 2 | 54 participants (Actual) | Interventional | 2011-04-01 | Completed |
| Phase II Study of Hyper-CVAD Plus Imatinib Mesylate (Gleevec, STI571) for Philadelphia-Positive Acute Lymphocytic Leukemia[NCT00038610] | Phase 2 | 54 participants (Actual) | Interventional | 2001-03-31 | Completed |
| Randomized Phase II Study of Clofarabine Alone Versus Clofarabine in Combination With Low-Dose Cytarabine in Previously Untreated Patients >= 60 Years With AML and High-Risk MDS[NCT00088218] | Phase 2 | 95 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Phase II Trial of Clofarabine and Cytarabine in Relapsed Standard-Risk AML and Untreated High-Risk MDS in Adult Patients, and Untreated AML in Selected Elderly Patients at High Risk of Anthracycline Toxicity[NCT00334074] | Phase 2 | 30 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Phase 2 Study Of Clofarabine With High Dose Cytarabine And G-CSF Priming In Adult Patients Less Than Age 65 With Newly Diagnosed Acute Myeloid Leukemia Or Advanced Myelodysplastic Syndrome and/or Advanced Myeloproliferative Neoplasm[NCT01101880] | Phase 2 | 50 participants (Actual) | Interventional | 2010-08-31 | Completed |
| Phase 2 Study of Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for the Treatment of Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia[NCT03118466] | Phase 2 | 41 participants (Actual) | Interventional | 2017-09-25 | Active, not recruiting |
| A Phase 1 Trial of the CD123 X CD3 DART Molecule Flotetuzumab (NSC#808294) in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia[NCT04158739] | Phase 1 | 16 participants (Actual) | Interventional | 2020-01-22 | Active, not recruiting |
| A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patie[NCT04029688] | Phase 1/Phase 2 | 183 participants (Anticipated) | Interventional | 2020-01-27 | Recruiting |
| B-NHL 2013 - Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents[NCT03206671] | Phase 3 | 650 participants (Anticipated) | Interventional | 2017-08-03 | Recruiting |
| Treatment Protocol for Relapsed Anaplastic Large Cell Lymphoma of Childhood and Adolescence[NCT00317408] | | 96 participants (Anticipated) | Interventional | 2004-04-30 | Active, not recruiting |
| A Randomized, Open Label, Phase 2 Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Versus Specified Physician's Choice in Patients ≥ 60 Years Old With Relapsed or Refractory Acute Myeloid Leukemia (AML) Who Are Ineligible for [NCT02088541] | Phase 2 | 317 participants (Actual) | Interventional | 2014-03-31 | Completed |
| AUTOLOGOUS, ALLOGENEIC, OR SYNGENEIC BONE MARROW TRANSPLANTATION IN HODGKIN'S DISEASE, NON-HODGKIN'S LYMPHOMA, AND MULTIPLE MYELOMA[NCT00002552] | Phase 2 | 40 participants (Anticipated) | Interventional | 1993-10-31 | Completed |
| AUTOLOGOUS STEM CELL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA IN SECOND REMISSION: A PHASE II STUDY[NCT00002768] | Phase 2 | 51 participants (Actual) | Interventional | 1996-06-30 | Completed |
| Chemotherapy and Azidothymidine, With or Without Radiotherapy, for High Grade Lymphoma in AIDS-Risk Group Members[NCT00000703] | | 45 participants | Interventional | | Completed |
| A PHASE III STUDY IN CHILDREN WITH UNTREATED ACUTE MYELOGENOUS LEUKEMIA (AML) OR MYELODYSPLASTIC SYNDROME (MDS)[NCT00002798] | Phase 3 | 880 participants (Actual) | Interventional | 1996-08-31 | Completed |
| EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY[NCT00002816] | Phase 3 | 120 participants (Anticipated) | Interventional | 1996-12-31 | Completed |
| TREATMENT OF ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: PHASE II TRIALS OF AN INDUCTION REGIMEN INCLUDING PEG-L-ASPARAGINASE, WITH OR WITHOUT PIXY, IN PREVIOUSLY UNTREATED PATIENTS, FOLLOWED BY ALLOGENEIC BONE MARROW TRANSPLANTATION OR FURTHER CHEMOTHERAPY IN FI[NCT00002665] | Phase 2 | 50 participants (Anticipated) | Interventional | 1995-07-31 | Completed |
| INDUCTION WITH ALL-TRANS RETINOIC ACID IN COMBINATION WITH IDARUBICIN AND INTENSIVE CONSOLIDATION FOLLOWED BY BONE MARROW TRANSPLANTATION OR A RANDOMIZED MAINTENANCE TREATMENT DEPENDING UPON THE AMOUNT OF MINIMAL RESIDUAL DISEASE IN ACUTE PROMYELOCYTIC LE[NCT00002701] | Phase 3 | 750 participants (Anticipated) | Interventional | 1995-10-31 | Active, not recruiting |
| A Randomised Study Comparing an Oral Regimen (Idarubicin and Etoposide) With an Intravenous Regimen (MAE) for Consolidation in Patients Over 55 Years With Acute Myeloid Leukaemia in First Complete Remission[NCT00003602] | Phase 3 | 400 participants (Anticipated) | Interventional | 1998-03-31 | Active, not recruiting |
| A Phase II Study of Intensive Methotrexate and Cytarabine Followed by High Dose Beam Chemotherapy With Autologous Peripheral Blood Progenitor Cell Transplantation in Patients With Newly Diagnosed Primary Central Nervous System Lymphoma[NCT00003632] | Phase 2 | 30 participants (Anticipated) | Interventional | 1998-09-30 | Completed |
| CAMP-010: PHASE I/II STUDY OF IN VIVO PURGING FOLLOWED BY HIGH DOSE CHEMOTHERAPY, AUTOLOGOUS HEMATOPOIETIC STEM CELL INFUSION AND IMMUNOTHERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA[NCT00002761] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 1996-02-29 | Withdrawn(stopped due to PI left institution) |
| Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Infants Less Than 1 Year of Age.[NCT00002785] | Phase 2 | 0 participants | Interventional | 1996-07-31 | Completed |
| A Phase I Study of G3139 (NSC 683428) in Combination With Salvage Chemotherapy for Treatment of Refractory and Relapsed Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL)[NCT00004862] | Phase 1 | 24 participants (Actual) | Interventional | 1999-10-31 | Completed |
| The Value of Dexamethasone Versus Prednisolone During Induction and Maintenance Therapy of Prolonged Versus Conventional Duration of L-Asparaginase Therapy During Consolidation and Late Intensification, and of Corticosteroid + VCR Pulses During Maintenanc[NCT00003728] | Phase 3 | 1,500 participants (Anticipated) | Interventional | 1998-12-31 | Active, not recruiting |
| Treatment of Relapsed Acute Myelogenous Leukemia Consisting of Intermediate Dose Cytosine Arabinoside (ARA-C) Plus Interspaced Continuous Infusion Idarubicin, Followed by Continuous Infusion of Low-Dose ARA-C, A Phase II Study by the EORTC-LCG[NCT00003758] | Phase 2 | 60 participants (Anticipated) | Interventional | 1998-12-31 | Active, not recruiting |
| An Investigator-Initiated Study To Evaluate Ara-C and Idarubicin in Combination With the Selective Inhibitor Of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Relapsed Or Refractory AML[NCT02249091] | Phase 2 | 42 participants (Actual) | Interventional | 2014-09-30 | Completed |
| Use of G-CSF Stimulated HLA-Identical Allogeneic Peripheral Blood Stem Cells for Patients With High Risk Acute Myelogenous Leukemia or CML in Blast Crisis[NCT00002833] | Phase 2 | 53 participants (Actual) | Interventional | 1994-10-31 | Completed |
| PROSPECTIVE RANDOMISED STUDY TO COMPARE LOW-DOSE INTERFERON-ALPHA-n1 (WELLFERON) +/- HYDROXYUREA VS HIGH-DOSE INTERFERON-ALPHA-n1 (WELLFERON) +/- HYDROXYUREA IN PATIENTS WITH NEWLY DIAGONISED CHRONIC PHASE CHRONIC MYELOID LEUKAEMIA[NCT00002869] | Phase 3 | 800 participants (Anticipated) | Interventional | 1995-04-30 | Active, not recruiting |
| A Phase I/II Combination Study of Topotecan, Fludarabine, Cytosine Arabinoside and G-CSF (T-FLAG) Induction Therapy in Patients With Poor Prognosis AML, MDS and Relapsed/Refractory ALL Followed by Maintenance of Either PBSC Transplant or 13 Cis-Retinoic A[NCT00003619] | Phase 1/Phase 2 | 0 participants | Interventional | 1998-02-28 | Completed |
| The Unrelated Donor Marrow Transplantation Trial[NCT00003187] | Phase 2/Phase 3 | 19 participants (Actual) | Interventional | 1995-05-31 | Completed |
| A Phase II Study of High Dose Late Intensification Therapy in Patients With Chemotherapy Sensitive Multiple Myeloma[NCT00004903] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Active, not recruiting |
| Phase 2, Randomized, Biomarker-driven Clinical Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With MCL-1 Dependence ≥30%[NCT02520011] | Phase 2 | 104 participants (Actual) | Interventional | 2016-03-14 | Terminated(stopped due to Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete.) |
| A Phase I Study of Metformin and Cytarabine for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia[NCT01849276] | Phase 1 | 2 participants (Actual) | Interventional | 2015-03-11 | Terminated(stopped due to Slow accrual) |
| Augmented Berlin-Frankfurt-Munster Therapy Plus Ofatumumab for Young Adults With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma[NCT02419469] | Phase 2 | 1 participants (Actual) | Interventional | 2015-11-13 | Terminated(stopped due to Slow Accrual) |
| Phase II Trial of Intensive, Short-Course Combination Chemotherapy in the Treatment of Newly Diagnosed Patients With Poor-Risk Nonlymphoblastic Lymphoma and Acute B-Lymphoblastic Leukemia and in Patients With Recurrent Non-Hodgkin's Lymphoma[NCT00002471] | Phase 2 | 0 participants | Interventional | 1990-02-28 | Completed |
| RANDOMIZED PHASE III STUDY OF INDUCTION (ICE VS MICE VS DCE) AND INTENSIVE CONSOLIDATION (IDIA VS NOVIA VS DIA) FOLLOWED BY BONE MARROW TRANSPLANTATION IN ACUTE MYELOGENOUS LEUKEMIA: AML 10 PROTOCOL[NCT00002549] | Phase 3 | 1,520 participants (Anticipated) | Interventional | 1993-11-30 | Active, not recruiting |
| PHASE II TRIAL OF POST-REMISSION THERAPY WITH HuM195 AND CYTOTOXIC CHEMOTHERAPY FOR ACUTE PROMYELOCYTIC LEUKEMIA[NCT00002609] | Phase 2 | 40 participants (Actual) | Interventional | 1994-08-31 | Completed |
| PROSPECTIVE CONTROLLED STUDY FOR THE OPTIMIZATION OF THERAPY IN CHRONIC MYELOID LEUKEMIA (CML): MULTICENTRIC STUDY FOR THE EVALUATION OF INTERFERON ALPHA VS ALLOGENIC BM TRANSPLANTATION WITH CHEMOTHERAPY IN CML[NCT00002771] | Phase 3 | 750 participants (Anticipated) | Interventional | 1995-01-31 | Active, not recruiting |
| High-Dose Cytarabine and Idarubicin Induction, High Dose Etoposide and Cyclophosphamide Intensification, Autologous Stem Cell Transplantation and Interleukin-2 Immune Modulation in Previously Untreated De Novo and Secondary Adult Myeloid Leukemia[NCT00002945] | Phase 3 | 61 participants (Actual) | Interventional | 1996-12-31 | Completed |
| A Phase II Study of Subcutaneous Bortezomib in Combination With Chemotherapy (VXLD) for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia[NCT01769209] | Phase 2 | 18 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Phase II Study of Decitabine and Cytarabine for Older Patients With Newly Diagnosed AML[NCT01829503] | Phase 2 | 44 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Phase II Study of Clofarabine and Cytarabine for Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Persistent Disease After Treatment With an Anthracycline and Cytarabine[NCT01960387] | Phase 2 | 2 participants (Actual) | Interventional | 2013-10-31 | Terminated(stopped due to lack of accrual) |
| A Phase II Study of Melphalan HCl for Injection (Propylene Glycol-free), Combined With Carmustine, Etoposide, and Cytarabine (BEAM Regimen) for Myeloablative Conditioning in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation[NCT01969435] | Phase 2 | 50 participants (Actual) | Interventional | 2014-03-19 | Completed |
| A Phase 1/2 Trial of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS)[NCT02044796] | Phase 1/Phase 2 | 199 participants (Actual) | Interventional | 2014-01-23 | Completed |
| Phase 1 Study of the Dual MDM2/MDMX Inhibitor ALRN-6924 in Pediatric Cancer[NCT03654716] | Phase 1 | 21 participants (Actual) | Interventional | 2018-11-01 | Completed |
| A Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leu[NCT01238211] | Phase 2 | 61 participants (Actual) | Interventional | 2010-12-14 | Completed |
| Treatment Protocol for Patients With Standard Risk Acute Myelogenous Leukemia and Its Variants: Induction Using High-Dose Cytarabine, Mitoxantrone and Ethyol; Consolidation With Cytarabine and Idarubicin and Maintenance With 13 Cis Retinoic Acid and Alpha[NCT00003405] | Phase 2 | 0 participants (Actual) | Interventional | 1998-04-30 | Withdrawn(stopped due to No enrollment) |
| Phase 3 Multicenter Randomized Trial to Evaluate Efficacy and Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. Therapy and Control Sub-groups in Older Patients With R/R AML[NCT03504410] | Phase 3 | 200 participants (Actual) | Interventional | 2018-11-12 | Terminated(stopped due to Futile) |
| Non-Hodgkin's Lymphoma T Cell Protocol[NCT00003423] | Phase 3 | 100 participants (Anticipated) | Interventional | 1995-05-31 | Active, not recruiting |
| Acute Myeloid Leukemia Salvage Therapy for Patients in First Relapse or Who Fail to Achieve an Initial Remission or Who Develop AML as a Second Malignant Neoplasm[NCT00002805] | Phase 2 | 115 participants (Actual) | Interventional | 1997-08-31 | Completed |
| A Randomized Prospective Study of Early Intensification Versus Alternating Triple Therapy for Patients With Poor Prognosis Lymphoma[NCT00002835] | Phase 3 | 116 participants (Actual) | Interventional | 1995-10-30 | Completed |
| HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR RELAPSED OR REFRACTORY ALL: A PHASE II STUDY OF A MULTIDRUG REGIMEN[NCT00002865] | Phase 2 | 25 participants (Actual) | Interventional | 1995-04-30 | Completed |
| A Phase II Trial of Multiple Cycles of Sequential High Dose Chemotherapy for Patients With Chemotherapy Sensitive Relapsed Non-Hodgkin's Lymphoma[NCT00003957] | Phase 2 | 3 participants (Actual) | Interventional | 1998-12-31 | Completed |
| Pilot Study of Intensive Chemotherapy Followed by Peripheral Blood Stem Cell Harvesting for Autotransplantation of Adults With Chronic Myelogenous Leukemia and High Risk Acute Leukemia[NCT00004905] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Completed |
| "Clinical Protocol for a Phase II Study of Leridistim (SC-70935) in Adult Patients (Age>55) With Acute Myeloid Leukemia (AML) Receiving Chemotherapy With the Cytarabine and Daunorubicin 7+3 Regimen"[NCT00004215] | Phase 2 | 0 participants | Interventional | 1999-08-31 | Completed |
| Phase II Study of Fludarabine + Idarubicin + Aracytine in Refractory or Relapsed ALL in Children[NCT00003729] | Phase 2 | 13 participants (Actual) | Interventional | 1998-12-31 | Terminated(stopped due to low accrual) |
| Phase I Study of UCN-01 and Cytarabine (ARA-C) in Patients With Acute Myelogenous Leukemia, and Myelodysplastic Syndromes[NCT00004263] | Phase 1 | 16 participants (Actual) | Interventional | 1999-12-31 | Completed |
| ALinC 17: Continuous Intensification for Very High Risk Acute Lymphocytic Leukemia (A.L.L.): A Pediatric Oncology Group Pilot Study[NCT00003783] | Phase 2 | 36 participants (Actual) | Interventional | 1999-03-31 | Completed |
| Randomized Study of Rituximab (Mabthera) in Patients With Relapsed Follicular Lymphoma Prior to High-Dose Therapy as In Vivo Purging and to Maintain Remission Following High-Dose Therapy[NCT00005589] | Phase 3 | 460 participants (Anticipated) | Interventional | 1999-10-31 | Completed |
| A Phase II Trial of Cisplatinum, Cytosine Arabinoside, Dexamethasone (DHAP) With Rituxan in Patients With Relapsed CD20+ B-Cell Non-Hodgkin's Lymphoma[NCT00005601] | Phase 2 | 58 participants (Actual) | Interventional | 2000-10-31 | Completed |
| A Phase I/II Study of Induction Chemotherapy With Daunorubicin, Cytarabine, Topotecan and Etoposide (DATE) for De Novo AML: In the Treatment of Young Patients Ages 16-59[NCT00005793] | Phase 1/Phase 2 | 41 participants (Actual) | Interventional | 1999-07-31 | Completed |
| Evaluation of Pretargeted Anti-CD20 Radioimmunotherapy Combined With BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk B-Cell Malignancies[NCT02483000] | Phase 1 | 3 participants (Actual) | Interventional | 2017-02-01 | Terminated(stopped due to Closed early due to lack of funding) |
| A Pilot Study of Mitoxantrone-Based Four Drug Reinduction in Combination With Bortezomib for Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma in Children and Young Adults[NCT02535806] | Phase 2 | 2 participants (Actual) | Interventional | 2015-07-31 | Terminated(stopped due to Funding source discontinued) |
| Phase I/II Study of Idarubicin, Cytarabine, and Nivolumab in Patients With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)[NCT02464657] | Phase 1/Phase 2 | 44 participants (Actual) | Interventional | 2015-07-31 | Completed |
| Phase 3 Randomized Trial of DFP-10917 vs Non-Intensive Reinduction (LoDAC, Azacitidine, Decitabine, Venetoclax Combination Regimens) or Intensive Reinduction (High & Intermediate Dose Cytarabine Regimens) for Acute Myelogenous Leukemia Patients in Second,[NCT03926624] | Phase 3 | 450 participants (Anticipated) | Interventional | 2019-11-22 | Recruiting |
| Autologous Bone Marrow Transplantation for Non-M3 Acute Myeloid Leukemia (AML) in First Remission in Patients NCT00534469] | Phase 2 | 60 participants (Actual) | Interventional | 2000-02-08 | Active, not recruiting |
| Phase Ib Trial of Gilteritinib in Combination With Mitoxantrone, Cladribine, Cytarabine and Filgrastim (GM-CLAG) for Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia[NCT05330377] | Phase 1 | 0 participants (Actual) | Interventional | 2023-03-31 | Withdrawn(stopped due to Sponsor withdrew funding) |
| A Phase II Study of Bortezomib and Vorinostat in Patients With Refractory or Relapsed MLL Rearranged Hematologic Malignancies[NCT02419755] | Phase 2 | 12 participants (Actual) | Interventional | 2015-04-14 | Terminated(stopped due to Accrual goals were no longer feasible based on restrictions imposed by the DSMB.) |
| Treatment Optimization in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma by Individualised, Targeted and Intensified Treatment - a Phase IV-trial With a Phase III-part to Evaluate Safety and Efficacy of Ne[NCT02881086] | Phase 3 | 1,000 participants (Actual) | Interventional | 2016-08-31 | Active, not recruiting |
| A Phase 1b Dose-escalation Study of SGN-CD33A in Combination With Standard-of-care for Patients With Newly Diagnosed Acute Myeloid Leukemia[NCT02326584] | Phase 1 | 116 participants (Actual) | Interventional | 2014-12-31 | Completed |
| AN OPEN-LABEL, RANDOMIZED PHASE 3 STUDY OF INOTUZUMAB OZOGAMICIN COMPARED TO A DEFINED INVESTIGATOR'S CHOICE IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)[NCT01564784] | Phase 3 | 326 participants (Actual) | Interventional | 2012-08-02 | Completed |
| A Phase I-II Study of Oxaliplatin, Fludarabine, and Cytarabine in Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes at First Relapse With Complete Remission Duration < 1 Year[NCT00480987] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2007-07-31 | Terminated(stopped due to Lack of support.) |
| Efficacy and Safety of Cladribine in Combination With G-CSF, Low-dose Cytarabine and Pegaspargase in Patients With Refractory/Relapsed Acute Lymphoblastic Leukemia: a Phase 2 Clinical Trial[NCT03318419] | Phase 2 | 50 participants (Anticipated) | Interventional | 2016-01-01 | Recruiting |
| The Feasibility of Safely Managing Patients Receiving Induction With Liposomal Daunorubicin and Cytarabine (CPX-351) for Acute Myeloid Leukemia (AML) in an Outpatient Environment[NCT03988205] | Phase 4 | 3 participants (Actual) | Interventional | 2019-08-28 | Terminated(stopped due to Low accrual) |
| NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma[NCT01451515] | Phase 2 | 23 participants (Actual) | Interventional | 2012-05-25 | Completed |
| A Multi-center Randomized Open-label Clinical Trial of Ara-C, Aclarubicin Combined With PEG-G-CSF for Initial Treatment of Acute Myeloid Leukemia Patients[NCT03045627] | Phase 2 | 120 participants (Anticipated) | Interventional | 2017-01-31 | Recruiting |
| A Phase 1/2, Open-label Randomized Study of Ulocuplumab (BMS-936564) in Combination With Low Dose Cytarabine in Subjects With Newly Diagnosed Acute Myeloid Leukemia[NCT02305563] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2015-01-27 | Terminated(stopped due to Business objectives have changed, slow accrual, the standard of care for the patient population changed and we were unable to accrue any longer.) |
| B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021)[NCT05518383] | Phase 4 | 300 participants (Anticipated) | Interventional | 2022-05-25 | Recruiting |
| RANDOMIZED PHASE III STUDY TO EVALUATE THE VALUE OF rHuG-CSF IN INDUCTION AND OF AN ORAL SCHEDULE AS CONSOLIDATION TREATMENT IN ELDERLY PATIENTS WITH ACUTE MYELOGENOUS LEUMEKIA (AML-13 PROTOCOL)[NCT00002719] | Phase 3 | 500 participants (Anticipated) | Interventional | 1995-12-31 | Completed |
| Phase I-II Study of Crenolanib Combined With Standard Salvage Chemotherapy, and Crenolanib Combined With 5-Azacitidine in Acute Myeloid Leukemia Patients With FLT3 Activating Mutations[NCT02400281] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2015-09-30 | Completed |
| Allogeneic Hematopoietic Stem Cell Transplantation as Initial Salvage Therapy for Patients With Primary Induction Failure Acute Myeloid Leukemia Refractory to High-Dose Cytarabine-Based Induction Chemotherapy[NCT02441803] | Phase 2 | 11 participants (Actual) | Interventional | 2015-09-14 | Active, not recruiting |
| A Multicenter，Open-label，Randomized Study on the Treatment of Elderly Chinese Acute Myeloid Leukemia Patients Aged 65 to 75 Years Old[NCT02432911] | | 300 participants (Anticipated) | Interventional | 2015-04-30 | Recruiting |
| A Phase I - II Study to Assess Safety and Efficacy of the Combination of Ponatinib With High or Intermediate-Dose Cytarabine as Consolidation Therapy for Patients With Intermediate-Risk Cytogenetic FLT3-ITD AML iIn First Complete Remission[NCT02428543] | Phase 1/Phase 2 | 49 participants (Actual) | Interventional | 2013-07-31 | Active, not recruiting |
| Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia[NCT00003079] | Phase 1 | 30 participants (Actual) | Interventional | 1997-09-30 | Completed |
| Phase 1 Study of Deferasirox in Acute Leukemia Patients Not Treated by Standard Chemotherapy Regimens[NCT02413021] | Phase 1 | 40 participants (Anticipated) | Interventional | 2016-05-31 | Not yet recruiting |
| A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Entospletinib in Combination With Intensive Induction and Consolidation Chemotherapy in Adults With Newly Diagnosed Nucleophosmin 1-mutated Acute Myeloid Le[NCT05020665] | Phase 3 | 15 participants (Actual) | Interventional | 2021-11-30 | Terminated(stopped due to Termination was due to significant challenges associated with study enrollment in a genetic subset of fit participants in the front-line acute myeloid leukemia (AML) setting and other challenges associated with post-COVID impacts.) |
| Treatment of Mature B-ALL and Burkitt Lymphoma (BL) in Adult Patients. BURKIMAB-14.[NCT05049473] | Phase 2 | 100 participants (Anticipated) | Interventional | 2014-01-31 | Recruiting |
| A Randomized Controlled Study of Dasatinib Combined With Reduced Intensive Consolidation Chemotherapy in Newly Diagosed Philadelphia Chromesome Positive Adult Lymphoblastic Leukemia[NCT05026229] | | 60 participants (Anticipated) | Interventional | 2021-09-06 | Recruiting |
| Phase II CCOP Trial of High Dose Methotrexate/ARA-C and HCVAD for Newly Diagnosed Nodular and Diffuse Mantle Cell Lymphoma and Their Blastic Variants[NCT00003311] | Phase 2 | 19 participants (Actual) | Interventional | 1998-05-20 | Completed |
| A Randomized 3-Arm Phase II Study Comparing 1.) Bendamustine, Rituximab and High Dose Cytarabine (BR/CR) 2.) Bendamustine, Rituximab, High Dose Cytarabine and Acalabrutinib (BR/CR-A), and 3.) Bendamustine, Rituximab and Acalabrutinib (BR-A) in Patients &l[NCT04115631] | Phase 2 | 360 participants (Actual) | Interventional | 2019-12-13 | Active, not recruiting |
| A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia[NCT00005962] | Phase 2 | 0 participants | Interventional | 2000-10-04 | Completed |
| PROSPECTIVE RANDOMISED STUDY TO COMPARE INTERFERON-ALPHA-n1 (WELLFERON) VS 'IDAC' CHEMOTHERAPY AND AUTOGRAFTING FOLLOWED BY INTERFERON ALPHA-n1 (WELLFERON) IN PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA[NCT00002868] | Phase 3 | 744 participants (Anticipated) | Interventional | 1997-11-20 | Completed |
| A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With[NCT01412879] | Phase 2 | 53 participants (Actual) | Interventional | 2011-11-30 | Completed |
| A Phase 1/2 Study of Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Subjects With Acute Myelogenous Leukemia Who Are ≥ 60 Years of Age and Who Are Not Eligible for Standard Anthracycline-Based Induction Therapy[NCT02287233] | Phase 1/Phase 2 | 94 participants (Actual) | Interventional | 2014-12-31 | Completed |
| Bortezomib Combined With Fludarabine and Cytarabine for Mantle Cell Lymphoma Patients：a Single Arm, Open-labelled, Phase 2 Study[NCT03016988] | Phase 2 | 50 participants (Anticipated) | Interventional | 2017-01-31 | Not yet recruiting |
| A Phase II Study of CLAG Regimen in Combination With Imatinib Mesylate (Gleevec) in Relapsed or Refractory Acute Myeloid Leukemia[NCT00955916] | Phase 2 | 38 participants (Actual) | Interventional | 2009-08-31 | Completed |
| A Phase II Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With High-risk Acute Myeloid Leukemia[NCT02560025] | Phase 2 | 42 participants (Actual) | Interventional | 2015-12-31 | Completed |
| Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I[NCT02553460] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2016-01-29 | Active, not recruiting |
| Phase 1-2 Safety and Efficacy Study of DACOGEN in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia[NCT01853228] | Phase 1/Phase 2 | 17 participants (Actual) | Interventional | 2013-10-22 | Terminated(stopped due to EMA/PDCO acknowledged that available results from this study do not support further clinical studies in relapsed/refractory AML paediatric patients.) |
| A Phase I/II Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Lymphoid Malignancies[NCT01921387] | Phase 1/Phase 2 | 20 participants (Actual) | Interventional | 2013-10-09 | Completed |
| Dasatinib Plus Multi-agent Chemotherapy for New Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia[NCT02523976] | Phase 2 | 30 participants (Actual) | Interventional | 2015-08-01 | Completed |
| A Randomized Controlled Study on the Efficacy and Safety of MA-BUCY2 Protocol in the Conditioning of Haploidentical Stem Cell Transplantation in Patients With High-risk Acute Myeloid Leukemia[NCT05814731] | | 264 participants (Anticipated) | Interventional | 2023-04-15 | Not yet recruiting |
| Multicenter Randomized Controlled Clinical Study of Mitoxantrone Hydrochloride Liposome Injection Combined With Carmustine, Etoposide and Cytarabine (Modified BEAM Protocol) for T Cell Lymphoma Underwent Autologous Stem Cell Transplantation[NCT05814718] | | 122 participants (Anticipated) | Interventional | 2023-04-15 | Not yet recruiting |
| A Phase 1 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms[NCT04797767] | Phase 1 | 20 participants (Anticipated) | Interventional | 2022-02-04 | Recruiting |
| Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblast[NCT03860844] | Phase 2 | 67 participants (Actual) | Interventional | 2019-08-06 | Terminated(stopped due to Study was prematurely stopped due to sponsor decision (stage 2 efficacy criteria not met); not due to safety concerns.) |
| A Phase 1, Open-label, Dose-escalation, Safety and Biomarker Prediction of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)[NCT03298984] | Phase 1 | 32 participants (Actual) | Interventional | 2017-09-25 | Completed |
| A Phase 3, Multicenter, Open-label, Randomized Study Comparing the Efficacy and Safety of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation[NCT02577406] | Phase 3 | 319 participants (Actual) | Interventional | 2015-12-30 | Active, not recruiting |
| A Single-Center Phase 1/2 Study of Single- or Fractioned-Dose Gemtuzumab Ozogamicin in Combination With G-CSF, Cladribine, Cytarabine, and Mitoxantrone for Previously Untreated Adult Acute Myeloid Leukemia or High-Grade Myeloid Neoplasm[NCT03531918] | Phase 1/Phase 2 | 66 participants (Actual) | Interventional | 2018-09-14 | Completed |
| A Multicenter Randomized Control Clinical Trail of Evaluating Effect of Demethylation Drug Combined With Chemotherapy in Patients With Intermediate-risk AML After Hematological Complete Remission[NCT03417427] | Phase 2 | 100 participants (Anticipated) | Interventional | 2018-02-01 | Recruiting |
| A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia or Refractory/Relapsed B-Cell Chronic Lymphocytic Leukemia[NCT00452374] | Phase 1/Phase 2 | 48 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Decitabine,Cytarabine(Ara-C) and Arsenic Trioxide(ATO) in the Treatment of Acute Myeloid Leukemia With p53 Mutations[NCT03381781] | Phase 2 | 100 participants (Anticipated) | Interventional | 2018-03-31 | Not yet recruiting |
| Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)[NCT02121418] | | 12 participants (Actual) | Interventional | 2014-06-30 | Completed |
| A PHASE IB/II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF VISMODEGIB IN RELAPSED/REFRACTORY ACUTE MYELOGENOUS LEUKEMIA (AML) AND RELAPSED/REFRACTORY HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS)[NCT01880437] | Phase 2 | 38 participants (Actual) | Interventional | 2013-09-30 | Terminated |
| Clinical Study on the Efficacy and Safety of Auto-HSCT in Adult Patients With Burkitt Lymphoma, Lymphoblastic Lymphoma, and Acute Lymphoblastic Leukemia Who Received TCCA Conditioning Regimen[NCT06060782] | Phase 1 | 28 participants (Anticipated) | Interventional | 2023-10-01 | Recruiting |
| BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus CEM (Carboplatin, Etoposide, Melphalan) in Lymphoma Patients as a Conditioning Regimen Before Autologous Hematopoietic Cell Transplantation[NCT05813132] | | 60 participants (Actual) | Interventional | 2022-12-01 | Completed |
| Randomized Phase 2 Trial of CPX-351 (Vyxeos) vs. CLAG-M (Cladribine, Cytarabine, G-CSF, and Mitoxantrone) in Medically Less-Fit Adults With Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm[NCT04195945] | Phase 2 | 60 participants (Anticipated) | Interventional | 2020-03-11 | Recruiting |
| LS1781: Phase 2 Trial of High Dose Intravenous Ascorbic Acid as an Adjunct to Salvage Chemotherapy in Relapsed / Refractory Lymphoma and Patients With Clonal Cytopenia of Undetermined Significance[NCT03418038] | Phase 2 | 55 participants (Anticipated) | Interventional | 2018-03-23 | Recruiting |
| Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma[NCT03117751] | Phase 2/Phase 3 | 790 participants (Actual) | Interventional | 2017-03-29 | Active, not recruiting |
| A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations[NCT02883049] | Phase 3 | 5,937 participants (Actual) | Interventional | 2012-02-29 | Active, not recruiting |
| Phase II Trial of Vosaroxin in Combination With Infusional Cytarabine in Patients With Untreated AML[NCT02658487] | Phase 2 | 42 participants (Actual) | Interventional | 2016-03-31 | Active, not recruiting |
| A Study of Combination of Venetoclax, Hypomethylation Agent and Low-dose Cytarabine as a Salvage Therapy in Patients With Acute Myeloid Leukemia Who Had Relapsed/Refractory Disease or Positive Minimal Residual Disease[NCT05362942] | Phase 2 | 52 participants (Anticipated) | Interventional | 2022-05-01 | Not yet recruiting |
| An Expanded Access Study for Venetoclax in Combination With Low-Dose Cytarabine in Treatment-Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Intensive Induction Therapy in Japan[NCT04509622] | Phase 3 | 14 participants (Actual) | Interventional | 2020-10-05 | Completed |
| Phase III, Multicenter, Randomized, Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients 60-75 Years of Age With Untreated High Risk (Secondary) AML[NCT01696084] | Phase 3 | 309 participants (Actual) | Interventional | 2012-12-13 | Completed |
| A Phase 1/2 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients With Myelodysplastic Syndrome (RAEB-2) or With Previously Untreated Acute Myeloid Leukemia[NCT00831766] | Phase 1/Phase 2 | 51 participants (Actual) | Interventional | 2009-06-25 | Completed |
| A Phase II Trial of Clofarabine and Cytarabine to Treat Minimal Residual Disease (MRD) in Acute Myeloid Leukemia[NCT00863434] | Phase 2 | 2 participants (Actual) | Interventional | 2009-02-28 | Terminated |
| Consolidation Therapy for Acute Myeloid Leukemia Guided by Leukemia Stem Cell Behavior[NCT01588951] | Phase 2/Phase 3 | 10 participants (Actual) | Interventional | 2013-12-31 | Terminated(stopped due to Low accrual) |
| A Single-arm, Prospective, Single-center, Phase II Clinical Study of Penpulimab Combined With RMA in the Treatment of Newly Diagnosed Primary CNS Lymphoma[NCT05347641] | Phase 2 | 23 participants (Anticipated) | Interventional | 2022-06-01 | Not yet recruiting |
| A Phase I Study of Venetoclax Combined With Vyxeos (CPX-351) for Children, Adolescents and Young Adults With Relapsed or Refractory Acute Leukemia[NCT03826992] | Phase 1 | 21 participants (Anticipated) | Interventional | 2018-12-27 | Recruiting |
| A TACL Phase 1/2 Study of PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma IND# 140730[NCT03817320] | Phase 1/Phase 2 | 31 participants (Anticipated) | Interventional | 2019-02-12 | Recruiting |
| A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia[NCT06124157] | Phase 3 | 680 participants (Anticipated) | Interventional | 2024-01-22 | Not yet recruiting |
| International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia[NCT01117441] | Phase 3 | 6,136 participants (Actual) | Interventional | 2010-06-30 | Completed |
| A Multicenter Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia: Testing Pharmacokinetically Individualized Doses of L-Asparaginase Following the DFCI Pediatric Consortium Protocol[NCT00136435] | Phase 2 | 100 participants (Anticipated) | Interventional | 2002-06-30 | Active, not recruiting |
| A Dose-finding Phase I Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Very Low-dose Cytarabine in Patients With AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation[NCT02957032] | Phase 1 | 30 participants (Anticipated) | Interventional | 2016-04-13 | Terminated(stopped due to New agents for the same indication impacted on patients' recruitment) |
| Venetoclax Combining Chidamide and Azacitidine (VCA) Regimen Followed by Dicitabine Combined With Liposome Mitoxantrone, Cytarabine, and G-CSF (D-MAG) Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) : A Multi[NCT05603884] | Phase 2 | 66 participants (Anticipated) | Interventional | 2022-12-01 | Recruiting |
| Prospective, Single-arm, Multicenter Exploratory Clinical Study of the Combination of Etoposide, Cytarabine and PEG-rhG-CSF (EAP Regimen) as First Line Mobilization Regimen of Hematopoietic Stem Cells in Patients With Hematological Malignancies[NCT05536154] | | 68 participants (Anticipated) | Interventional | 2022-11-01 | Recruiting |
| Standard Chemotherapy (CHOP Regimen) Versus Sequential High-Dose Chemotherapy With Autologous Stem Cell Transplantation in Patients With Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas and Poor Prognostic Factors: A Randomized Phase III Study (MISTRAL)[NCT00003215] | Phase 3 | 400 participants (Anticipated) | Interventional | 1997-04-30 | Completed |
| Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Alpha Interferon (IFN-A), Low-Dose Cytosine Arabinoside (ARA-C), and Homoharringtonine (HHT)[NCT00003239] | Phase 2 | 90 participants (Actual) | Interventional | 1998-03-31 | Completed |
| A Phase II Study of Daunomycin and ARA-C Given by Continuous IV Infusion With PSC-833 for Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) in Patients of Age 56 or Older[NCT00004217] | Phase 2 | 55 participants (Anticipated) | Interventional | 2000-02-29 | Completed |
| [NCT00004643] | Phase 2 | 10 participants | Interventional | 1995-02-28 | Completed |
| ALINC #17 Treatment for Patients With Low Risk Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Phase III Study[NCT00005585] | Phase 3 | 838 participants (Actual) | Interventional | 2000-04-30 | Completed |
| ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study[NCT00005603] | Phase 3 | 276 participants (Actual) | Interventional | 2000-03-31 | Completed |
| Protocol for Patients With Newly Diagnosed Better Risk Acute Lymphoblastic Leukemia (ALL): A POG Pilot Study[NCT00003671] | Phase 2 | 59 participants (Actual) | Interventional | 1998-12-31 | Completed |
| Treatment of Poor Risk Myelodysplasia With the Combination of Amifostine, Topotecan and ARA-C: A Phase II Study[NCT00003827] | Phase 2 | 25 participants (Anticipated) | Interventional | 1999-01-31 | Active, not recruiting |
| Prospective Phase II Study of a High Dose, Short Course Regimen (R-CODOX-M/IVAC) Including CNS Penetration and Intensive IT Prophylaxis in HIV-Associated Burkitt's and Atypical Burkitt's Lymphoma[NCT00392834] | Phase 2 | 34 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Phase II Study of Alvocidib (NSC 649890, Flavopiridol) in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Newly Diagnosed, Previously Untreated, Poor-Risk Acute Myelogenous Leukemias[NCT00407966] | Phase 2 | 45 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Randomized Phase II Study Comparing Two Administration Schedules of Flavopiridol (Alvocidib, NSC 649890, IND 46, 211) Given in Timed Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone Hydrochloride for Adults With Newly Diagnosed, P[NCT00795002] | Phase 2 | 78 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Phase II Study of Omacetaxine (OM) and Low Dose Cytarabine (LDAC) in Older Patients With Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS)[NCT01272245] | Phase 2 | 36 participants (Actual) | Interventional | 2011-07-31 | Completed |
| Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia[NCT00844298] | Phase 2 | 91 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Phase II Trial of Ifosfamide, Etoposide, Cytarabine, and Methotrexate (IVAM) Chemotherapy for Refractory or Relapsed Diffuse Large B Cell Lymphoma[NCT03383406] | Phase 2 | 30 participants (Anticipated) | Interventional | 2016-12-01 | Enrolling by invitation |
| A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy or Idarubicin With High Dose Cytarabine (IA) Versus IA With Vorinostat (NSC-701852) (IA + V) in Younger Patients With Previously Untreated Acute Myeloid Leukemia (AML)[NCT01802333] | Phase 3 | 754 participants (Actual) | Interventional | 2013-02-12 | Completed |
| A Phase II Study of V-BEAM (Bortezomib, Carmustine, Etoposide, Cytarabine, and Melphalan) as Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation for Multiple Myeloma[NCT01653418] | Phase 2 | 10 participants (Actual) | Interventional | 2012-09-30 | Terminated(stopped due to Due to the high rate of morbidity and mortality) |
| A Phase 3 Randomized Trial of Inotuzumab Ozogamicin (NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy[NCT03959085] | Phase 3 | 4,772 participants (Anticipated) | Interventional | 2019-10-31 | Recruiting |
| Mature B-Cell Lymphoma And Leukemia Study III[NCT01046825] | Phase 2/Phase 3 | 128 participants (Actual) | Interventional | 2010-09-09 | Active, not recruiting |
| Phase II Study on Safety and Activity of a Short Term Intensified Chemo-immunotherapy Combination in HIV-positive Patients Affected by Burkitt Lymphoma[NCT01516593] | Phase 2 | 19 participants (Actual) | Interventional | 2011-11-30 | Completed |
| Risk-stratified Sequential Treatment of Post-transplant Lymphoproliferative Disease (PTLD) With 4 Courses of Rituximab SC Followed by 4 Courses of Rituximab SC, 4 Courses of Rituximab SC Combined With CHOP-21 or 6 Courses of Rituximab SC Combined With Alt[NCT02042391] | Phase 2 | 60 participants (Actual) | Interventional | 2015-02-03 | Completed |
| A Pilot Study of Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma[NCT02728531] | Phase 1 | 18 participants (Actual) | Interventional | 2016-04-18 | Completed |
| Phase III Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy of the Addition of Crenolanib to Salvage Chemotherapy Versus Salvage Chemotherapy Alone in Subjects ≤ 75 Years of Age With Relapsed/Refractory FLT3 Mutated Acute Myelo[NCT03250338] | Phase 3 | 322 participants (Anticipated) | Interventional | 2018-06-05 | Recruiting |
| Y Zevalin, BEAM and Rituximab In Autologous Stem Cell Transplantation (ASCT) For Lymphoma[NCT01538472] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Efficacy and Safety of Decitabine in Combination With Low-dose Cytarabine as Inductive Treatment in Newly Diagnosed Elderly Patients With Acute Myeloid Leukemia[NCT02985372] | Phase 3 | 30 participants (Anticipated) | Interventional | 2016-12-31 | Enrolling by invitation |
| A Phase 3, Randomized, Open-label, Multicenter Study Comparing Ponatinib Versus Imatinib, Administered in Combination With Reduced-Intensity Chemotherapy, in Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ [NCT03589326] | Phase 3 | 245 participants (Actual) | Interventional | 2018-10-04 | Active, not recruiting |
| MidOStaurin + Gemtuzumab OzogAmIcin Combination in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)[NCT04385290] | Phase 1/Phase 2 | 214 participants (Anticipated) | Interventional | 2020-09-04 | Recruiting |
| A Phase I/II Study of CP-4055 in Patients With Refractory/Relapsed Hematologic Malignancies[NCT00405743] | Phase 1/Phase 2 | 153 participants (Actual) | Interventional | 2006-05-31 | Completed |
| AML-02: Study of the Activity and Safety of the Addition of Omacetaxine to the Standard-of-Care Induction Therapy Regimen of Cytarabine and Idarubicin in Newly-Diagnosed AML Patients[NCT02440568] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2015-06-05 | Terminated |
| Phase I Study of Pacritinib and Chemotherapy in Patients With Acute Myeloid Leukemia and FLT3 Mutations[NCT02323607] | Phase 1 | 13 participants (Actual) | Interventional | 2016-01-12 | Completed |
| Epacadostat With Cladribine and Cytarabine (ECC) in Relapsed / Refractory AML Patients Fit for Intensive Chemotherapy; a Phase I Study.[NCT03491579] | Phase 1 | 0 participants (Actual) | Interventional | 2018-12-31 | Withdrawn(stopped due to IMP will not be further developed) |
| Epacadostat With Idarubicin and Cytarabine (EIC) for First-line Treatment of AML Patients Fit for Intensive Chemotherapy; a Phase I Study[NCT03444649] | Phase 1 | 0 participants (Actual) | Interventional | 2018-09-30 | Withdrawn(stopped due to IMP will not be further developed) |
| International Protocol for the Treatment of Childhood Anaplastic Large Cell Lymphoma[NCT00006455] | Phase 3 | 885 participants (Actual) | Interventional | 1999-11-26 | Completed |
| Reduced Intensity Conditioning Regimen for Elderly or High Comorbidity Burden Patients Receiving Haploidentical Hematopoietic Stem Cell Transplantation[NCT03412409] | Phase 2 | 50 participants (Anticipated) | Interventional | 2018-02-01 | Recruiting |
| Master Screening and Reassessment Protocol (MSRP) for the NCI MyeloMATCH Clinical Trials[NCT05564390] | Phase 2 | 750 participants (Anticipated) | Interventional | 2024-02-01 | Not yet recruiting |
| A Randomized Phase II Study Comparing Cytarabine + Daunorubicin (7 + 3) to (Daunorubicin and Cytarabine) Liposome, Cytarabine + Daunorubicin + Venetoclax, and Azacitidine + Venetoclax in Patients Aged 59 or Younger With High-Risk (Adverse) Acute Myeloid L[NCT05554406] | Phase 2 | 268 participants (Anticipated) | Interventional | 2024-02-01 | Not yet recruiting |
| A Measurable Residual Disease (MRD) Driven, Phase II Study of Venetoclax Plus Chemotherapy for Newly Diagnosed Younger Patients With Intermediate Risk Acute Myeloid Leukemia: A Tier 1 MYELOMATCH Clinical Trial[NCT05554393] | Phase 2 | 153 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting |
| Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents[NCT03020030] | Phase 3 | 560 participants (Actual) | Interventional | 2017-03-03 | Active, not recruiting |
| A Phase 3, Open-Label, Multicenter, Randomized Study of SKLB1028 Versus Salvage Chemotherapy in Patients With FLT3-mutated Acute Myeloid Leukemia Refractory to or Relapsed After First-line Treatment（ALIVE）[NCT04716114] | Phase 3 | 315 participants (Anticipated) | Interventional | 2021-03-24 | Recruiting |
| A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-center Trial[NCT00005803] | Phase 1/Phase 2 | 76 participants (Actual) | Interventional | 1999-09-30 | Completed |
| A Phase 2 Study of WEE1 Inhibition With AZD1775 Alone or Combined With Cytarabine in Patients With Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome[NCT02666950] | Phase 2 | 3 participants (Actual) | Interventional | 2017-05-05 | Completed |
| A Prospective, Randomized, Controlled Trial of Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Patients With Acute Myeloid Leukemia With t(8;21)[NCT03026842] | Phase 4 | 180 participants (Anticipated) | Interventional | 2017-01-31 | Active, not recruiting |
| Safety and Efficacy of Chemotherapy Combined With Adoptive Transfer of Human Leukocyte Antigen (HLA)-Haploidentical Donor Lymphocyte Infusion (DLI) in Older Patients With Righ-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)[NCT02046122] | Phase 1/Phase 2 | 19 participants (Actual) | Interventional | 2014-07-31 | Completed |
| OAG and Decitabine for Newly Diagnosed Acute Myeloid Leukemia Patients Greater Than or Equal to 65 Years of Age[NCT02029417] | Phase 2 | 2 participants (Actual) | Interventional | 2014-07-31 | Terminated(stopped due to Major revisions needed in study) |
| A PHASE 1 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, EFFICACY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF PF-04449913 (GLASDEGIB), AN ORAL HEDGEHOG INHIBITOR, ADMINISTERED AS A SINGLE AGENT IN JAPANESE PATIENTS WITH SELECT HEMATOLOGIC MALIGNANCIES AND IN [NCT02038777] | Phase 1 | 48 participants (Actual) | Interventional | 2014-03-25 | Active, not recruiting |
| A Phase I/II Study of Liposomal Cytarabine and Daunorubicin (CPX-351) in Combination With Quizartinib in Patients With Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)[NCT04128748] | Phase 1/Phase 2 | 52 participants (Anticipated) | Interventional | 2020-05-27 | Recruiting |
| A Combination of Cladribine, Idarubicin, Cytarabine (CLIA) and Quizartinib for the Treatment of Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS))[NCT04047641] | Phase 1/Phase 2 | 80 participants (Anticipated) | Interventional | 2019-10-22 | Recruiting |
| A Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination With Standard Intensive AML Induction/Consolidation Therapy With FLAG-IDA in Patients With Newly Diagnosed or Relapsed/Refractory AML[NCT03214562] | Phase 1/Phase 2 | 116 participants (Anticipated) | Interventional | 2017-09-26 | Recruiting |
| A Feasibility Study of Myeloablative BEAM Allogeneic Transplantation Followed by Oral Ixazomib Maintenance Therapy in Patients With Relapsed High-Risk Multiple Myeloma[NCT02504359] | Phase 1 | 11 participants (Actual) | Interventional | 2015-07-20 | Completed |
| A Phase I Study to Evaluate the Safety and Tolerability of Gemtuzumab Ozogamicin and Midostaurin When Used in Combination With Standard Cytarabine and Daunorubicin Induction for Newly Diagnosed FLT3-mutated Acute Myeloid Leukemia[NCT03900949] | Phase 1 | 18 participants (Anticipated) | Interventional | 2019-03-13 | Recruiting |
| Phase II Study of Pedi-cRIB: Mini-Hyper-CVD With Condensed Rituximab, Inotuzumab Ozogamicin and Blinatumomab (cRIB) for Relapsed Therapy for Pediatric With B-Cell Lineage Acute Lymphocytic Leukemia[NCT05645718] | Phase 2 | 27 participants (Anticipated) | Interventional | 2023-07-14 | Recruiting |
| Phase 1 A/B Study of LY2606368 in Combination With Cytarabine and Fludarabine in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HRMDS)[NCT02649764] | Phase 1 | 15 participants (Actual) | Interventional | 2016-05-04 | Completed |
| A Randomized Trial Using a Modified COG ABFM Regimen Backbone to Investigate Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)[NCT05681260] | Phase 3 | 200 participants (Anticipated) | Interventional | 2023-02-06 | Recruiting |
| Prospective, Single-arm, Multicenter Exploratory Clinical Study of the Combination of Etoposide, Cytarabine and PEG-rhG-CSF (EAP Regimen) on Hematopoietic Stem Cell Mobilization in Poor Mobilization Patients With Hematological Malignancies[NCT05510089] | | 62 participants (Anticipated) | Interventional | 2022-09-01 | Recruiting |
| BEAM + 131Iodine-Anti-B1 Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for the Treatment of Recurrent Non-Hodgkin's Lymphoma[NCT00574509] | Phase 1 | 34 participants (Actual) | Interventional | 1996-03-04 | Completed |
| A Current Practice Study of Rituxan in Patient Receiving BEAM Chemotherapy and Autologous Blood Stem Cell Transplantation for High Risk Lymphoma or Hodgkin's Disease[NCT01702961] | | 75 participants (Actual) | Interventional | 2002-06-30 | Completed |
| International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol C Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric [NCT05745714] | Phase 1/Phase 2 | 26 participants (Anticipated) | Interventional | 2023-10-01 | Not yet recruiting |
| Feasibility of Outpatient Daily High Dose Cytarabine as Consolidation Therapy for Older Patients With Acute Myeloid Leukemia[NCT02101983] | | 11 participants (Actual) | Interventional | 2011-05-31 | Completed |
| A Pilot Study of a Sequential Regimen of Intensive Chemotherapy Followed by Autologous or Allogeneic Transplantation for Refractory Lymphoma (Non-Hodgkin's and Hodgkin's) and Phase 2 Expansion Cohort[NCT02059239] | Phase 1/Phase 2 | 34 participants (Actual) | Interventional | 2014-06-04 | Completed |
| A Phase I-II, Multicentre, Open Label Clinical Trial to Assess the Safety and Tolerability of the Combination of Low-dose Cytarabine or Azacitidine, Plus Venetoclax and Quizartinib in Newly Diagnosed Acute Myeloid Leukemia Patients Aged Equal or More Than[NCT04687761] | Phase 1/Phase 2 | 84 participants (Anticipated) | Interventional | 2020-11-04 | Recruiting |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
Complete Remission (CR) Rate (Including CR With Incomplete Recovery)
"Participants who achieved morphological complete remission with or without incomplete blood count recovery.~Per the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia, morphologic complete remission requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL." (NCT00840177)
Timeframe: Up to 5 years after registration
| Intervention | Participants (Count of Participants) |
|---|
| Initial Cohort: Relapsed AML With Previous Remission ≥ 3 Month | 27 |
| Poor-risk Cohort: MDS Transformed to AML | 14 |
| Poor-risk Cohort: Refractory/Relapsed AML, < 6 Mths Remission | 14 |
Overall Survival (OS)
OS is calculated for all participants from the date of initial registration on study until death from any cause. Observations for participants last known to be alive were censored. (NCT00840177)
Timeframe: OS assessed for up to 5 years, median OS reported
| Intervention | months (Median) |
|---|
| Initial Cohort: Relapsed AML With Previous Remission ≥ 3 Month | 10 |
| Poor-risk Cohort: MDS Transformed to AML | 10 |
| Poor-risk Cohort: Refractory/Relapsed AML, < 6 Mths Remission | 4 |
Relapse-free Survival (RFS)
"RFS is calculated for participants who have achieved a complete response (CR) or CR with incomplete blood count recovery (CRi). RFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.~Per the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia, morphologic complete remission requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL." (NCT00840177)
Timeframe: RFS assessed for up to 5 years, median RFS reported
| Intervention | months (Median) |
|---|
| Initial Cohort: Relapsed AML With Previous Remission ≥ 3 Month | 9 |
| Poor-risk Cohort: MDS Transformed to AML | 19.4 |
| Poor-risk Cohort: Refractory/Relapsed AML, < 6 Mths Remission | 2.7 |
Frequency and Severity of Toxicity as Assessed by NCI CTCAE Version 3.0
Number of patients with Grade 3-5 adverse events that were possibly, probably or definitely related to study drug are reported by given type of adverse event (NCT00840177)
Timeframe: Up to 5 years post registration
| Intervention | Participants (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT | Acidosis (metabolic or respiratory) | Albumin, serum-low (hypoalbuminemia) | Alkaline phosphatase | Alkalosis (metabolic or respiratory) | Anorexia | Bilirubin (hyperbilirubinemia) | Blood/Bone Marrow-Other (Specify) | Bone marrow cellularity | Calcium, serum-low (hypocalcemia) | Carbon monoxide diffusion capacity (DL(co)) | Cardiac General-Other (Specify) | Cardiac-ischemia/infarction | Colitis, infectious (e.g., Clostridium difficile) | Conduction abnormality - Asystole | Confusion | Constitutional Symptoms-Other (Specify) | Creatinine | Diarrhea | Distention/bloating, abdominal | Dry mouth/salivary gland (xerostomia) | Dyspnea (shortness of breath) | Edema: limb | Esophagitis | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Glucose, serum-high (hyperglycemia) | Hemoglobin | Hemorrhage, GI - Duodenum | Hemorrhage, GU - Vagina | Hemorrhage, pulmo/upper resp- Bronchopulmonary NOS | Hemorrhage, pulmonary/upper respiratory - Nose | Hemorrhage/Bleeding-Other (Specify) | Hypertension | Hypotension | Hypoxia | Ileus, GI (functional obstruction of bowel) | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | Inf (clin/microbio) w/Gr 3-4 neuts - Kidney | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | Inf (clin/microbio) w/Gr 3-4 neuts - Meninges | Inf (clin/microbio) w/Gr 3-4 neuts - Sinus | Inf (clin/microbio) w/Gr 3-4 neuts - Skin | Inf (clin/microbio) w/Gr 3-4 neuts - Small bowel | Inf (clin/microbio) w/Gr 3-4 neuts - Stomach | Infection with unknown ANC - Blood | Infection with unknown ANC - Lung (pneumonia) | Infection with unknown ANC - Mucosa | Infection with unknown ANC - Sinus | Infection with unknown ANC - Small bowel NOS | Infection-Other (Specify) | Left ventricular diastolic dysfunction | Leukocytes (total WBC) | Lipase | Lymphopenia | Magnesium, serum-high (hypermagnesemia) | Mental status | Mucositis/stomatitis (clinical exam) - Oral cavity | Mucositis/stomatitis (clinical exam) - Pharynx | Mucositis/stomatitis (functional/symp) - Oral cav | Musculoskeletal/Soft Tissue-Other (Specify) | Nausea | Necrosis, GI - Small bowel NOS | Neutrophils/granulocytes (ANC/AGC) | Obstruction, GI - Small bowel NOS | Ocular/Visual-Other (Specify) | Opportunistic inf associated w/gt=Gr 2 lymphopenia | Pain - Abdomen NOS | Pain - Bone | Pain - Esophagus | Pain - Extremity-limb | Pain - Oral cavity | Pain - Peritoneum | Phosphate, serum-low (hypophosphatemia) | Platelets | Pleural effusion (non-malignant) | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Pulmonary hypertension | Pulmonary/Upper Respiratory-Other (Specify) | Rash/desquamation | Renal failure | Renal/Genitourinary-Other (Specify) | SVT and nodal arrhythmia - Atrial fibrillation | SVT and nodal arrhythmia - Atrial flutter | Sodium, serum-high (hypernatremia) | Sodium, serum-low (hyponatremia) | Syncope (fainting) | Typhlitis (cecal inflammation) | Ulcer, GI - Duodenum | Ulceration | Vomiting | Weight loss |
|---|
| Initial Cohort: Relapsed AML With Previous Remission ≥ 3 Month | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 2 | 2 | 1 | 2 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 3 | 0 | 0 | 2 | 0 | 1 | 3 | 20 | 1 | 11 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 4 | 1 | 0 | 5 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 16 | 1 | 6 | 0 | 1 | 0 | 0 | 1 | 0 | 2 | 0 | 14 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 17 | 0 | 0 | 6 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 2 | 0 |
,| Poor-risk Cohort: MDS Transformed to AML | 2 | 3 | 1 | 3 | 0 | 1 | 1 | 2 | 1 | 0 | 5 | 4 | 0 | 1 | 1 | 0 | 0 | 2 | 3 | 4 | 2 | 1 | 1 | 2 | 0 | 2 | 18 | 2 | 14 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 4 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 0 | 1 | 1 | 0 | 11 | 0 | 5 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 15 | 1 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 4 | 16 | 1 | 2 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 |
,| Poor-risk Cohort: Refractory/Relapsed AML, < 6 Mths Remission | 2 | 1 | 0 | 6 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 8 | 0 | 0 | 2 | 0 | 0 | 2 | 32 | 0 | 21 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 3 | 0 | 7 | 1 | 1 | 6 | 1 | 0 | 0 | 0 | 1 | 4 | 0 | 1 | 0 | 0 | 0 | 0 | 17 | 0 | 9 | 0 | 0 | 1 | 1 | 1 | 0 | 3 | 0 | 16 | 0 | 0 | 2 | 0 | 1 | 1 | 1 | 3 | 0 | 2 | 19 | 0 | 0 | 3 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 |
Overall Survival
Overall Survival rate at 1 year. Time to death is from date of registration to date of death due to any cause. (NCT00041132)
Timeframe: assessed after cycle 4, after completion of treatment, then every 3 months for 2 years, then every 6 months thereafter until 5 years
| Intervention | percentage of participants (Number) |
|---|
| Hyper-CVAD + MTX/Ara-C + Rituximab | 92 |
Progression-free Survival
Progression-Free Survival (PFS) rate at 1 year. PFS measured from date of registration to date of first observation of progressive disease or death due to any cause. Progressive disease is a 50% increase in the sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed if a complete response (confirmed, or unconfirmed) was not previously achieved; appearance of a new lesion/site; unequivocal progression of non-measurable disease; or death due to disease without prior documentation of progression. (NCT00041132)
Timeframe: assessed after cycle 4, after completion of treatment, then every 3 months until 1 year after registration
| Intervention | percentage of participants (Number) |
|---|
| Hyper-CVAD + MTX/Ara-C + Rituximab | 90 |
Response
Complete (CR), complete unconfirmed (CRU) and partial responses (PR). CR is complete disappearance of all measurable and non-measurable disease with the exception of nodes; no new lesions; previously enlarged organs must have regressed in size; and if bone marrow positive at baseline, it must be negative. CRU is complete disappearance of all measurable and non-measurable disease; regressed, non-palpable organs; and one or more exceptions not qualifying for CR (see protocol section 10). PR applies to patients with at least one measurable lesion who do not qualify for CR or CRU. PR is a 50% decrease in sum of products of greatest diameters (SPD) for up to six identified dominant lesions identified at baseline; no new lesions; no increase in the size of liver, spleen or other nodes; and splenic and hepatic nodules must have regressed in size by at least 50% in SPD. (NCT00041132)
Timeframe: assessed after cycle 4 and after completion of treatment (168 days)
| Intervention | participants (Number) |
|---|
| Hyper-CVAD + MTX/Ara-C + Rituximab | 42 |
Response
Anti tumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan. Assessed by physical examination appropriate imaging studies. Bone marrow aspirate/biopsy must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Gallium scans must be negative if initially positive. (NCT00354107)
Timeframe: Week 4
| Intervention | percent (Number) |
|---|
| Treatment (Monoclonal Antibody Therapy, Chemotherapy) | 50 |
Event Free Survival (EFS)
Survival is defined as the minimum time from study entry to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm. Patients without report of such events where censored at last contact. This will be used to compute event free survival (EFS). (NCT00302003)
Timeframe: At 60 months
| Intervention | Probability of survival (Number) |
|---|
| Group 1 | 0.79 |
Event Free Survival Without Receiving Radiation Therapy (EFSnoRT).
Survival is defined as the minimum time from study entry to requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact. Patients who achieve less than CR after 3 cycles of AV-PC will require IFRT and hence will satisfy this definition at the time of response evaluation. Patients who achieve a CR but who relapse will receive addition chemotherapy and IFRT or intense retrieval and hence will satisfy this definition at the time of the first relapse of Hodgkin disease. This endpoint will be used to compute event free survival without receiving radiation therapy (EFSnoRT). (NCT00302003)
Timeframe: At 60 months
| Intervention | Probability of survival (Number) |
|---|
| Group 1 | 0.49 |
Intensive Therapy Free Survival (ITFS).
Survival is defined as the minimum time from study entry to a relapse of higher risk at any time, any relapse following treatment with protocol mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm. This will be used to compute intensive therapy free survival (ITFS). Patients without report of such events where censored at last contact. This differs from traditional EFS in that relapse after AVPC* x3 therapy alone that does not place the patient in a higher risk category is not considered a treatment failure. In this definition, higher-risk relapse refers to relapse involving sites and extent of disease that place the patient in the current COG definition of intermediate or high-risk disease. If a patient with CR who experiences a LR relapse is not retreated with protocol-mandated chemotherapy and IFRT, subsequent disease relapses will nevertheless be counted in the analysis of the treatment strategy. (NCT00302003)
Timeframe: At 60 months
| Intervention | Probability of survival (Number) |
|---|
| Group 1 | 0.89 |
Overall Survival
Survival is defined as time from study entry to death due to any cause. Patients alive at last contact where censored at last contact. (NCT00302003)
Timeframe: At 60 months
| Intervention | Probability of survival (Number) |
|---|
| Group 1 | 0.99 |
Complete Remission (CR)
complete remission (CR) Disappearance of all clinical evidence of leukemia for a minimum of four weeks. The patient should have a neutrophil count > 1,000 x 10^6/1, a platelet count > 100,000 x 10^9/1, no circulating blasts, and < than or = to blasts on bone marrow differential in a qualitatively normal or hypercellular marrow. Progressive disease or failure: Increasing bone marrow infiltrate or development of organ failure or extramedullary infiltrates due to leukemia. (NCT00002766)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Complete Remission | Complete Response (CR) | Failure | Failure-Progression | Relapse |
|---|
| All-2 | 50 | 14 | 5 | 8 | 1 |
,| L-20 | 50 | 11 | 14 | 10 | 0 |
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
"Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT:~Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue.~In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days~Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours~Liver function test abnormalities that did not resolve to Grade 2 within 10 days~Infection that resulted from unexpectedly complicated prolonged myelosuppression~Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days." (NCT03135028)
Timeframe: Cycle 1 (28-day cycle)
| Intervention | percentage of participants (Number) |
|---|
| ENTO 400 mg | 0.0 |
Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT
(NCT03135028)
Timeframe: Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
| Intervention | percentage of participants (Number) |
|---|
| ENTO 400 mg | 100.0 |
Plasma Concentration of ENTO
Plasma concentration of drug (ENTO) over different time points is reported. (NCT03135028)
Timeframe: Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 Day 8, predose | Cycle 1 Day 8, 1 hour postdose | Cycle 1 Day 8, 2 hours postdose | Cycle 1 Day 8, 3 hours postdose | Cycle 1 Day 8, 4 hours postdose | Cycle 1 Day 8, 6 hours postdose | Cycle 1 Day 8, 8 hours postdose | Cycle 1 Day 8, 12 hours postdose |
|---|
| ENTO 400 mg | 921.9 | 1395.7 | 1892.7 | 1529.1 | 1350.0 | 1139.3 | 1075.9 | 855.1 |
2 Year Relapse Free Survival (RFS)
Comparison of 2 year RFS in patient with detectable LSCs in the marrow at the end of consolidation to the 2 year RFS of patients without detectable LSCs. IWG Criteria (Cheson 2003) was utilized to classify relapse, with relapse defined as ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease, or disease presence determined by a physician upon clinical assessment. (NCT02927938)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| eLSC- (Evaluable Cohort) | NA |
Number of Patients Who Achieve a CD4 Count > 200/Micro-liters
Determine the number of patients who achieve a CD4 count > 200/micro-liters by 60 days after transplant. (NCT00429416)
Timeframe: Through 60 Days Post Transplant
| Intervention | participants (Number) |
|---|
| LLME to Decrease GVHD Following HSC T | 13 |
Rate of Engraftment of Non-Myeloablative Transplants
Determine the engraftment rate of non-myeloablative transplants using CD34+ stem cells and LLME treated CD34- products. (NCT00429416)
Timeframe: Through 30 days post-transplant
| Intervention | participants (Number) |
|---|
| LLME to Decrease GVHD Following HSC T | 13 |
Rate of Serious Infectious Complications
"Determine the rate of serious infectious complications. A serious infection will be defined as any requiring hospitalization or parenteral therapy.~CD4 counts will be measured monthly for the first 3 months after transplant." (NCT00429416)
Timeframe: Through 3 months post-transplant
| Intervention | participants (Number) |
|---|
| LLME to Decrease GVHD Following HSC T | 2 |
Safety of CD34+ Stem Cell Infusions Followed by LLME as Measured by 100-Day Mortality
"Determine the safety of CD34+ stem cell infusions followed by the LLME treated CD34- fraction. This includes monitoring the patients for any side effects associated with the LLME treated cell infusion or any other unexpected adverse events.~This regimen will be gauged as to its safety using 100 day mortality as the measured endpoint. Deaths from all causes will be included." (NCT00429416)
Timeframe: Through 100 days post-transplant or death
| Intervention | participants (Number) |
|---|
| LLME to Decrease GVHD Following HSC T | 1 |
Incidence of Grade II-IV Acute Graft-Versus-Host-Disease (GVHD)
Determine the incidence of grade II-IV acute GVHD after administration of grafts when combined with Cyclosporine/Mycophenolate Mofetil for GVHD prophylaxis. GVHD assessments occur daily as an in patient and at each out patient visit. (NCT00429416)
Timeframe: Through 24 months post-treatment
| Intervention | participants (Number) |
|---|
| Developed grade II-IV GVHD | Developed cGVHD (Chronic GVHD) |
|---|
| LLME to Decrease GVHD Following HSC T | 3 | 1 |
Duration of Any Hematologic Improvement
The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Median) |
|---|
| Azacitidine | 13.57 |
| Conventional Care | 5.18 |
Kaplan-Meier Estimate for Median Time to Transformation to Acute Myeloid Leukemia (AML) or Death From Any Cause, Whichever Occurred First
The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Median) |
|---|
| Azacitidine | 13.02 |
| Conventional Care | 7.61 |
Kaplan-Meier Estimates for Median Time to Death From Any Cause
Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Number) |
|---|
| Azacitidine | 24.46 |
| Conventional Care | 15.02 |
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML) Based on the Last Bone Marrow Assessment
A sensitivity analysis of time to transformation to AML during the entire study was performed based on the last bone marrow assessment. Patients were censored based on the last bone marrow assessment. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Median) |
|---|
| Azacitidine | 17.80 |
| Conventional Care | 11.48 |
Kaplan-Meier Estimates for Median Time to Transformation to Acute Myeloid Leukemia (AML)
The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Median) |
|---|
| Azacitidine | 20.66 |
| Conventional Care | 15.44 |
Number of Infections Per Treatment Year Requiring Intravenous Antibiotics, Antifungals or Antivirals
The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | infections per treatment year (Number) |
|---|
| Azacitidine | 0.16 |
| Conventional Care | 0.24 |
Number of Participants Who Died
Count of participants who died during the study (NCT00071799)
Timeframe: 42 months
| Intervention | participants (Number) |
|---|
| Azacitidine | 82 |
| Conventional Care | 113 |
Time to Disease Progression, Relapse After Complete or Partial Remission, or Death From Any Cause
The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Median) |
|---|
| Azacitidine | 14.13 |
| Conventional Care | 8.82 |
Number of Participants Considered Hematologic Responders by Investigator Determinations Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS)
"Investigator determined responses followed IWG criteria for~complete remission(CR): repeat bone marrow show <5% myeloblasts, and peripheral blood evaluations lasting >=2 months of hemoglobin(>110 g/L), neutrophils(>=1.5x10^9/L), platelets(>=100x10^9/L), blasts (0%) and no dysplasia~partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by >=50% or a less advanced FAB classification from pretreatment~stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months." (NCT00071799)
Timeframe: Day 1 to 42 months
| Intervention | participants (Number) |
|---|
| Overall (Complete + Partial Remission) | Complete Remission | Partial Remission | Stable Disease |
|---|
| Azacitidine | 51 | 30 | 21 | 75 |
,| Conventional Care | 21 | 14 | 7 | 65 |
Number of Participants in Different Categories of Adverse Experiences During Core Study Period
Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | participants (Number) |
|---|
| Patients with >=1 treatment emergent AE (TEAE) | Patients with >=1 treatment related TEAE | Patients with >=1 serious TEAE | Patients with >=1 serious treatment related TEAE | Patients w TEAE leading to discontinued treatment | Patients w TEAE leading to dose reduction | Patients w TEAE leading to dose interruption |
|---|
| Azacitidine | 175 | 169 | 114 | 43 | 22 | 20 | 82 |
,| Best Supportive Care Only | 97 | 1 | 71 | 0 | 4 | 0 | 0 |
,| Low-dose Cytarabine | 44 | 34 | 27 | 13 | 6 | 2 | 12 |
,| Standard Chemotherapy | 19 | 19 | 14 | 13 | 2 | 0 | 0 |
Number of Participants Showing Hematologic Improvement Using International Working Group (IWG 2000) Criteria for Myelodysplastic Syndrome (MDS) Assessed by Independent Review Committee
"IWG 2000 Criteria: Pretreatment=hemoglobin <100g/L or RBC transfusion-dependent, platelet count <100x10^9/L or platelet transfusion dependent, absolute neutrophil count <1.5x10^9/L.~Erythroid response: Major->20g/L increase or transfusion independent. Minor- 10-20g/L increase or >=50% decrease in transfusion requirements.~Platelet response: Major-absolute increase of >=30x10^9/L or platelet transfusion independence. Minor->=50% increase.~Neutrophil response: Major->=100% increase or an absolute increase of >0.5x10^9/L. Minor->=100% increase and absolute increase of <0.5x10^9/L." (NCT00071799)
Timeframe: Day 1 to 42 months
| Intervention | participants (Number) |
|---|
| Any Improvement n=177, 178 | Erythroid Response - Major n=157, 160 | Erythroid Response - Minor n=157, 160 | Platelet Response - Major n=141, 129 | Platelet Response - Minor n=138, 127 | Neutrophil Response - Major n=131, 111 | Neutrophil Response - Minor n=131, 111 |
|---|
| Azacitidine | 87 | 62 | 2 | 46 | 6 | 25 | 5 |
,| Conventional Care | 51 | 17 | 1 | 18 | 4 | 20 | 9 |
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | participants (Number) |
|---|
| Baseline Dependent; On-Treatment Independent | Baseline Dependent; On-Treatment Dependent |
|---|
| Azacitidine | 16 | 22 |
,| Conventional Care | 11 | 16 |
Summary of Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | participants (Number) |
|---|
| Baseline Independent; On-Treatment Independent | Baseline Independent; On-Treatment Dependent |
|---|
| Azacitidine | 126 | 15 |
,| Conventional Care | 102 | 50 |
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | participants (Number) |
|---|
| Baseline Dependent; On-Treatment Independent | Baseline Dependent; On-Treatment Dependent |
|---|
| Azacitidine | 50 | 61 |
,| Conventional Care | 13 | 101 |
Summary of Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline
Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent. (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | participants (Number) |
|---|
| Baseline Independent; On-Treatment Independent | Baseline Independent; On-Treatment Dependent |
|---|
| Azacitidine | 58 | 10 |
,| Conventional Care | 37 | 28 |
Summary of Subgroup Analyses for Kaplan-Meier Estimates for Time to Death From Any Cause
"Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.~Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification." (NCT00071799)
Timeframe: Day 1 (randomization) to 42 months
| Intervention | months (Number) |
|---|
| Age <65 years | Age >= 65 years | Age >= 75 years | Gender: Male | Gender: Female | FAB: Refractory anemia with excess blasts (RAEB) | FAB: RAEB in transformation | WHO: RAEB 1 | WHO: RAEB 2 | WHO: Other (AML, CMMoL-1 and 2, indeterminate) | IPSS: Intermediate 2 | IPSS: High |
|---|
| Azacitidine | 11.31 | 24.46 | 8.92 | 24.46 | 25.11 | 34.66 | 17.25 | 11.54 | 21.11 | 20.46 | 34.66 | 19.21 |
,| Conventional Care | 7.87 | 13.87 | 6.20 | 15.02 | 14.85 | 15.21 | 15.25 | 6.72 | 15.02 | 15.25 | 16.89 | 14.52 |
Incidence of Recurrent Disease
Number of patients that have disease recurrence. (NCT00054327)
Timeframe: at day 100 post transplant
| Intervention | participants (Number) |
|---|
| Regimen A | 4 |
| Regimen B-1 | 2 |
| Regimen B-2 | 0 |
| Regimen B-3 | 1 |
| Regimen C | 2 |
| Regimen D | 0 |
Number of Patients With Overall Survival at 2 Years.
(NCT00054327)
Timeframe: at 2 years from transplant
| Intervention | participants (Number) |
|---|
| Regimen A | 5 |
| Regimen B-1 | 2 |
| Regimen B-2 | 2 |
| Regimen B-3 | 1 |
| Regimen C | 5 |
| Regimen D | 1 |
Rates of Durable Engraftment
Number of days that patients take to reach engraftment defined as time to hematologic engraftment will be defined as ANC >500/µl and platelets >20K/µl without transfusion support. (NCT00054327)
Timeframe: at day 42
| Intervention | days (Mean) |
|---|
| Regimen A | 17.9 |
| Regimen B-1 | 15.75 |
| Regimen B-2 | 13 |
| Regimen B-3 | 18.25 |
| Regimen C | 13.9 |
| Regimen D | 10.5 |
Toxicity as Measured by CTC v2.0
Number of patients that experience grade 3 or above toxicity. See serious adverse event list for toxicities. (NCT00054327)
Timeframe: at 100 days post transplant
| Intervention | participants (Number) |
|---|
| Regimen A | 0 |
| Regimen B-1 | 0 |
| Regimen B-2 | 1 |
| Regimen B-3 | 2 |
| Regimen C | 2 |
| Regimen D | 0 |
Graft-versus-host Disease (GVHD)
Number of patients that develop acute graft-versus-host disease by grades 0-4. Grade O is no development of GVHD. Grade 1-4 is increase severity of skin, liver and gut involvement with 1 being least severe and 4 being most severe. (NCT00054327)
Timeframe: at 100 days post transplant
| Intervention | participants (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Regimen A | 0 | 2 | 6 | 2 | 0 |
,| Regimen B-1 | 1 | 1 | 2 | 0 | 0 |
,| Regimen B-2 | 1 | 0 | 1 | 0 | 1 |
,| Regimen B-3 | 1 | 0 | 0 | 3 | 0 |
,| Regimen C | 1 | 1 | 5 | 3 | 0 |
,| Regimen D | 0 | 0 | 0 | 0 | 2 |
Duration of Response
"Response date to loss of response or last follow up. Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR.~Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L).~Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts." (NCT03518112)
Timeframe: Time from the first day of treatment assessed up to 3 years, 1 month
| Intervention | Months (Median) |
|---|
| Treatment (Blinatumomab, Combination Chemotherapy) | 4.4 |
Event Free Survival (EFS) Where Events Defined as no Response, Loss of Response, or Death
"Time from date of treatment start until the date of first objective documentation of disease-relapse. Relapse and resistant disease will be defined based on morphological assessment of bone marrow and peripheral blood.~Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR.~Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L).~Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts." (NCT03518112)
Timeframe: Time from the first day of treatment assessed up to 3 years, 1 month
| Intervention | Months (Median) |
|---|
| Treatment (Blinatumomab, Combination Chemotherapy) | 5.7 |
Number of Participants Negative for Minimal Residual Disease (MRD)
Minimal Residual Disease (MRD) was assessed by flow cytometry. MRD negativity: Absence of detectable leukemia using multiparameter flow cytometry with a sensitivity of NCT03518112)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Blinatumomab, Combination Chemotherapy) | 4 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT03518112)
Timeframe: Time from the first day of treatment assessed up to 3 years, 1 month
| Intervention | Months (Median) |
|---|
| Treatment (Blinatumomab, Combination Chemotherapy) | 16.7 |
Participants With a Response
"defined as the percentage of patients achieving complete response (CR) or CR with inadequate count recovery (CRi). Complete Remission (CR): Normalization of the peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above, and platelet count of 100 x 10^9/L. Complete resolution of all sites of extramedullary disease is required for CR.~Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets < 100 x 10^9/L; neutrophils < 1 x 10^9/L)." (NCT03518112)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Blinatumomab, Combination Chemotherapy) | 4 |
Liposome-encapsulated Cytarabine Area Under the Curve
Geometric mean liposome-encapsulated cytarabine area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | (NANOGRAM x HOUR) / MILLILITER (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 4418582.5 |
Liposome-encapsulated Cytarabine Clearance
Geometric mean liposome-encapsulated cytarabine clearance following IV infusion will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | MILLILITER / HOUR (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 71.76 |
Liposome-encapsulated Cytarabine Time of Maximum Concentration
Median liposome-encapsulated cytarabine time of maximum observed plasma concentration will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | HOUR (Median) |
|---|
| Treatment (CPX-351 and FLAG) | 5 |
Liposome-encapsulated Cytarabine Volume of Distribution
Geometric mean liposome-encapsulated cytarabine volume of distribution following IV infusion will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | MILLILITER (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 4158.0 |
Liposome-encapsulated Daunorubicin Area Under the Curve
Geometric mean liposome-encapsulated daunorubicin area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | (NANOGRAM x HOUR) / MILLILITER (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 1288010.3 |
Liposome-encapsulated Daunorubicin Clearance
Geometric mean liposome-encapsulated daunorubicin clearance following IV infusion will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | MILLILITER / HOUR (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 94.7 |
Liposome-encapsulated Daunorubicin Time of Maximum Concentration
Median liposome-encapsulated daunorubicin time of maximum observed plasma concentration will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | HOUR (Median) |
|---|
| Treatment (CPX-351 and FLAG) | 2 |
Liposome-encapsulated Daunorubicin Volume of Distribution
Geometric mean liposome-encapsulated daunorubicin volume of distribution following IV infusion will be determined for patients in the dose-finding phase. (NCT02642965)
Timeframe: Prior to infusion on day 5 and, 45 and 90 minutes post day 5 infusion of cycle 1
| Intervention | MILLILITER (Geometric Mean) |
|---|
| Treatment (CPX-351 and FLAG) | 3827.7 |
Number of Participants With a Dose-limiting Toxicity
Number of patients in the dose-finding phase with a dose-limiting toxicity, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. (NCT02642965)
Timeframe: 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (CPX-351 and FLAG) | 1 |
Percentage of Responders (Complete Response or Complete Remission With Partial or Incomplete Platelet Recovery) After First Cycle of Therapy
Response (complete response or complete remission with partial or incomplete platelet recovery) after first cycle of therapy, where response is assessed using the revised Acute Myeloid Leukemia International Working Group Criteria. Percentage of responders is calculated by the total of number of patients with complete response or complete remission with partial or incomplete platelet recovery divided by the number of patients evaluable for response after the first cycle. 95% confidence interval is determined using a binomial exact method. (NCT02642965)
Timeframe: Up to 4 weeks
| Intervention | Percentage of responders (Number) |
|---|
| Treatment (CPX-351 and FLAG) | 75.68 |
Percentage of Responders (Complete Response or Complete Remission With Partial Platelet Recovery) After up to 2 Cycles
Best response (complete response or complete remission with partial platelet recovery) after up to 2 cycles of therapy, where response is assessed using the revised Acute Myeloid Leukemia International Working Group Criteria. Percentage of responders is calculated using the methods of Jung and Kim. 90% confidence interval is determined using the methods of Koyama and Chen. (NCT02642965)
Timeframe: Up to 8 weeks
| Intervention | Percantage of best responders (Number) |
|---|
| Treatment (CPX-351 and FLAG) | 68.30 |
Event-free Survival of Patients on Maintenance Randomization (Period 2)
Number of patients who develop EFS event during maintenance randomization (period 2) (NCT00078949)
Timeframe: during the period 2 (up to10 years)
| Intervention | participants (Number) |
|---|
| Maintenance | 53 |
| Observation | 65 |
Response Rate of Patients After 2 Courses of Chemotherapy
The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population). (NCT00078949)
Timeframe: After 2 cycle of treatment
| Intervention | percentage of response (Number) |
|---|
| Salvage GDP | 45.2 |
| Salvage DHAP | 44.0 |
Toxic Effect
Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details. (NCT00078949)
Timeframe: 48 months
| Intervention | Participants (Count of Participants) |
|---|
| Salvage GDP | 36 |
| Salvage DHAP | 26 |
| Maintenance | 16 |
| Observation | 8 |
Transplantation Rate of Patients After 2 Courses of Chemotherapy
Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients (NCT00078949)
Timeframe: During period 1 (salvage chemotherapy)
| Intervention | percentage of transplantation (Number) |
|---|
| Salvage GDP | 51.0 |
| Salvage DHAP | 48.9 |
Cumulative Incidence of Neutrophil Recovery
Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) > 500 neutrophils/μL following the expected nadir. (NCT01141712)
Timeframe: Day 28
| Intervention | percentage of participants (Number) |
|---|
| Autologous Transplant | 97.5 |
Cumulative Incidence of Platelet Recovery
Platelet recovery is defined as a platelet count greater than 20,000/μL for the first of two consecutive labs with no platelet transfusions 7 days prior. (NCT01141712)
Timeframe: Day 100
| Intervention | percentage of participants (Number) |
|---|
| Autologous Transplant | 92.5 |
Number of Participants Experiencing Infections
Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any. (NCT01141712)
Timeframe: Year 1
| Intervention | participants (Number) |
|---|
| Autologous Transplant | 22 |
Number of Participants Experiencing Toxicity
Toxicities will be defined by using the version 3.0 NCI Common Terminology Criteria for Adverse Events (CTCAE) criteria. Only grade 3 and higher toxicities will be collected. (NCT01141712)
Timeframe: Year 2
| Intervention | participants (Number) |
|---|
| Autologous Transplant | 9 |
Progression-Free Survival (PFS)
The time to this event is the time from enrollment until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first. Progression-free survival (PFS) will be estimated using the Kaplan Meier product limit estimator. The PFS probability and confidence interval will be calculated at two years post-transplant. (NCT01141712)
Timeframe: Year 2
| Intervention | percentage of participants (Number) |
|---|
| Autologous Transplant | 79.8 |
Relapse/Progression
Relapse is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. Progression is defined as a lymph node with a diameter of the short axis of less than 1.0 cm must increase by >= 50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis. (NCT01141712)
Timeframe: Year 2
| Intervention | percentage of participants (Number) |
|---|
| Autologous Transplant | 12.5 |
Treatment-Related Mortality (TRM)
TRM is defined as death occurring in a patient from causes other than relapse or progression. A cumulative incidence curve will be computed along with a 95% confidence interval at 100 days post-transplant. (NCT01141712)
Timeframe: Day 100
| Intervention | percentage of participants (Number) |
|---|
| Autologous Transplant | 5.2 |
Complete Remission (CR) and/or Partial Response (PR)
The frequencies and proportions of patients who have a CR or PR. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease and no new sites. (NCT01141712)
Timeframe: Day 100
| Intervention | participants (Number) |
|---|
| CR | PR | Relapse/Progression |
|---|
| Autologous Transplant | 36 | 1 | 2 |
Hematologic Function
Hematologic function will be defined as ANC > 1500 neutrophils/μL, Hemoglobin> 10g/dL without transfusion support, and platelets > 100,000/μL (NCT01141712)
Timeframe: Days 100 and 365
| Intervention | participants (Number) |
|---|
| Day 100 | Day 365 |
|---|
| Autologous Transplant | 11 | 23 |
HIV Single-Copy Polymerase Chain Reaction (PCR)
HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics. (NCT01141712)
Timeframe: Baseline, Days 100, 180, 365, and 730
| Intervention | copies/mL (Median) |
|---|
| Baseline | Day 100 | Day 180 | Day 365 | Day 730 |
|---|
| Autologous Transplant | 80 | 298 | 84 | 97 | 130 |
Immunologic Reconstitution
Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA) (NCT01141712)
Timeframe: Year 1
| Intervention | mg/dL (Median) |
|---|
| IgG | IgA | IgM |
|---|
| Autologous Transplant | 1090 | 123 | 48.5 |
Overall Survival (OS)
Assess the OS after autologous hematopoietic stem cell transplantation (HCT) for chemotherapy-sensitive aggressive B cell lymphoma or Hodgkin's lymphoma in patients with HIV using BEAM for pre-transplant conditioning. The primary analysis will consist of estimating the 1 year OS probability from the time of transplantation based on the Kaplan-Meier product limit estimator. The 1 year and 2 year OS and confidence interval will be calculated. (NCT01141712)
Timeframe: Year 1 and 2
| Intervention | percentage of participants (Number) |
|---|
| 1 year | 2 years |
|---|
| Autologous Transplant | 87.3 | 82 |
Area Under the Plasma Concentration Versus Time Curve of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Median (Range) of the area under the plasma concentration versus time curve of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level measured pre-dose, end of infusion, 4-6 hours, and 24 hours post-dose infusion on Days 1 and 5. (NCT03813147)
Timeframe: Up to 5 days
| Intervention | hr*ng/mL (Median) |
|---|
| Stratum 1 With 20 mg/m^2 | 1004.9 |
| PK With 20 mg/m^2 | 1047.4 |
Elimination Half-life of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Median (Range) of the elimination half-life of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level measured pre-dose, end of infusion, 4-6 hours, and 24 hours post-dose infusion on Days 1 and 5. (NCT03813147)
Timeframe: Up to 5 days
| Intervention | Hour (Median) |
|---|
| Stratum 1 With 20 mg/m^2 | 4.7 |
| PK With 20 mg/m^2 | 5.5 |
Maximum Concentration of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Median (Range) of the maximum concentration of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level measured pre-dose, end of infusion, 4-6 hours, and 24 hours post-dose infusion on Days 1 and 5. (NCT03813147)
Timeframe: Up to 5 days
| Intervention | ng/mL (Median) |
|---|
| Stratum 1 With 20 mg/m^2 | 248.5 |
| PK With 20 mg/m^2 | 213 |
Maximum Time to Concentration of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Median (Range) of the maximum time to concentration of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level measured pre-dose, end of infusion, 4-6 hours, and 24 hours post-dose infusion on Days 1 and 5. (NCT03813147)
Timeframe: Up to 5 days
| Intervention | Hour (Median) |
|---|
| Stratum 1 With 20 mg/m^2 | 1.2 |
| PK With 20 mg/m^2 | 1.1 |
Number of Participants With Adverse Events Attributable to MLN4924 (Pevonedistat)
Frequency of patients with at least one grade 3 adverse event at least possibly attributable to MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level. (NCT03813147)
Timeframe: Up to 70 days
| Intervention | Participants (Count of Participants) |
|---|
| Stratum 1 With 20 mg/m^2 | 6 |
| PK With 20 mg/m^2 | 6 |
Number of Participants With Antitumor Activity of MLN4924 (Pevonedistat)
Frequency of participants with best overall response by dose level of PR or CR for MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction Per Response Evaluation Criteria for CR (M1 bone marrow (< 5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral blood counts (ANC > 1000/uL and platelet count > 100,000/uL), CRp (M1 bone marrow (< 5% blasts) and no evidence of circulating blasts or extramedullary disease and with recovery of ANC > 1000/uL and platelet transfusion independence), CRi (M1 bone marrow (<5% blasts) and no evidence of circulating blasts or extramedullary disease and with ANC < 1000/uL or platelet count < 100,000/uL without platelet transfusion independence), or PR (M2 marrow status (> 5% or < 25% blasts cells) and at least 50% decrease in bone marrow blast percent from baseline. (NCT03813147)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Stratum 1 With 20 mg/m^2 | 1 |
| PK With 20 mg/m^2 | 2 |
Number of Participants With Dose Limiting Toxicities of MLN4924 (Pevonedistat)
Frequency of patients with dose limiting toxicity in the first cycle of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level among patients in the dose escalation cohort. (NCT03813147)
Timeframe: Up to 35 days
| Intervention | Participants (Count of Participants) |
|---|
| Stratum 1 With 20 mg/m^2 | 1 |
| PK With 20 mg/m^2 | 2 |
Total Plasma Clearance of MLN4924 (Pevonedistat) Added to the 3-drug Backbone of Azacitidine (Aza), Fludarabine, and Cytarabine Re-induction for Pediatric Patients With Recurrent/Refractory AML and MDS
Median (Range) of the total plasma clearance of MLN4924 (pevonedistat) added to the 3-drug backbone of azacitidine (aza), fludarabine, and cytarabine re-induction for pediatric patients with recurrent/refractory AML and MDS by dose level measured pre-dose, end of infusion, 4-6 hours, and 24 hours post-dose infusion on Days 1 and 5. (NCT03813147)
Timeframe: Up to 5 days
| Intervention | L/h/m^2 (Median) |
|---|
| Stratum 1 With 20 mg/m^2 | 20.1 |
| PK With 20 mg/m^2 | 19.2 |
Overall Response Rate After Two Cycles of ROAD
The overall response rate is defined as the percentage of patients who achieve a response after two cycles of oxaliplatin with rituximab, cytarabine, and dexamethasone (ROAD). A response was considered a Complete Response (CR) or Partial Response (PR) as defined by the NCI Sponsored International Working Group (IWG). CR: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities PR: ≥ 50% decrease in SPD of the six largest dominant nodes or nodal masses. (NCT00166439)
Timeframe: Up to 42 days
| Intervention | percentage of patients (Number) |
|---|
| Treatment (ROAD) | 58 |
Overall Survival
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT00166439)
Timeframe: Up to 10 years
| Intervention | months (Median) |
|---|
| Treatment (ROAD) | 26 |
Progression-free Survival
The progression-free survival 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. Progression is defined by the NCI Sponsored IWG as a ≥ 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or nonresponders and/or Appearance of any new lesion during or at the end of therapy. (NCT00166439)
Timeframe: Up to 10 years
| Intervention | months (Median) |
|---|
| Treatment (ROAD) | 11 |
Circulating Leukemia Cells in Peripheral Blood Change From Prior to the Methotrexate Infusion to Three Days After Between Two Arms (4 Hours vs. 24 Hours)
"White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count~Measurement: Percentage change of leukemia cells from baseline" (NCT00137111)
Timeframe: Immediately before the methotrexate infusion and three days after subsequent infusion
| Intervention | Percent change (Mean) |
|---|
| 4 hr | -44 |
| 24 hr | -50 |
Continuous Complete Remission Since Week 56 Therapy.
CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate. (NCT00137111)
Timeframe: Median follow up time (range) 4.5 (1 to 7.8) years
| Intervention | Percentage of participants (Number) |
|---|
| Patients With High Risk of CNS Relapse | 92.2 |
Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours).
Children were randomly assigned to receive initial single-agent treatment with HDMTX (1g/m^2) as either a 24-hour infusion or a 4-hour infusion and the outcome measure was the accumulation of MTXPG in leukemia cells. (NCT00137111)
Timeframe: 42 hours after start of high dose methotrexate infusion (HDMTX)
| Intervention | pmol/1,000,000,000 cells (Mean) |
|---|
| 4 hr | 1688 |
| 24 hr | 2521 |
Overall Event-free Survival (EFS)
EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate. (NCT00137111)
Timeframe: Median follow-up time (range) 5.6 (1.3 to 8.9) years
| Intervention | Percentage of Participants (Number) |
|---|
| Total Therapy | 87.3 |
Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells
Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of CASP1 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray. (NCT00137111)
Timeframe: Pre-treatment
| Intervention | arbitrary units (Median) |
|---|
| Prednisolone-sensitive cells | Prednisolone-resistant cells |
|---|
| Total Therapy | 341.3 | 447.9 |
Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells
Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of NLRP3 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray. (NCT00137111)
Timeframe: Pre-treatment
| Intervention | arbitrary units (Median) |
|---|
| Prednisolone-sensitive cells | Prednisolone-resistant cells |
|---|
| Total Therapy | 41.2 | 110.7 |
Minimal Residual Disease (MRD)
Detection of MRD at end of induction where positive MRD was defined as one or more leukemic cell per 10,000 mononuclear bone-marrow cells (>=0.01%). (NCT00137111)
Timeframe: End of Induction (Day 46 MRD measurement)
| Intervention | participants (Number) |
|---|
| Negative <0.01% | Positive >= 0.01% |
|---|
| Total Therapy | 390 | 102 |
Percentage of Participants Experiencing Grade 3-5 Toxicity
Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria). (NCT00133991)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| R-CVP + HiCy | 21 |
Event-free Survival
Percentage of participants alive without relapse at 1 year and 3 years. (NCT00133991)
Timeframe: 1 year and 3 years
| Intervention | percentage of participants (Number) |
|---|
| 1 year | 3 years |
|---|
| R-CVP + HiCy | 52 | 52 |
Overall Response Rate
Number of participants who have a complete or partial remission (2007 International Working Group criteria). (NCT00133991)
Timeframe: Up to 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete remission | Partial remission |
|---|
| R-CVP + HiCy | 11 | 2 |
Overall Survival
Percentage of participants alive at 1 year and at 3 years. (NCT00133991)
Timeframe: 1 year and 3 years
| Intervention | percentage of participants (Number) |
|---|
| 1 year | 3 years |
|---|
| R-CVP + HiCy | 57 | 57 |
Relapse Pattern
Percentage of participants experiencing central nervous system (CNS) and systemic relapse. (NCT00133991)
Timeframe: Up to 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Systemic relapse only | Systemic and CNS relapse |
|---|
| R-CVP + HiCy | 3 | 2 |
Number of Participants Treatment-Emergent Adverse Events Reported During Consolidation Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier. (NCT02834390)
Timeframe: Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Participants with TEAEs | Infections and Infestations | Lung infection | Skin infection | Upper respiratory tract infection | Blood and Lymphatic System Disorders | Febrile neutropenia | Nervous System Disorders | Dysgeusia | Gastrointestinal Disorders | Diarrhoea | Nausea | Stomatitis | Skin and Subcutaneous Tissue Disorders | Rash | Rash maculo-papular | General Disorders & Administration Site Conditions | Oedema peripheral | Investigations | Platelet count decreased | White blood cell count decreased | Alanine aminotransferase increased | Electrocardiogram QT prolonged | Injury, Poisoning, and Procedural Complications | Contusion | Fall |
|---|
| Quizartinib 20 mg/Day | 2 | 1 | 0 | 1 | 1 | 2 | 2 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Quizartinib 40 mg/Day | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 |
Number of Participants Treatment-Emergent Adverse Events Reported During Induction Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 1 up to 35 days after last dose in Cycle 2 (each cycle 28 days), up to approximately 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Participants with TEAEs | Infections and Infestations | Pneumonia | Skin infection | Staphylococcal bacteraemia | Blood and Lymphatic System Disorders | Febrile neutropenia | Anaemia | Leukopenia | Neutropenia | Thrombocytopenia | Immune Disorders | Hypersensitivity | Metabolism and Nutrition Disorders | Decreased appetite | Hypoalbuminaemia | Hypokalaemia | Hypomagnesaemia | Hyponatraemia | Hypophosphataemia | Hypouricaemia | Tumour lysis syndrome | Nervous System Disorders | Dysgeusia | Dizziness | Eye Disorders | Photophobia | Cardiac Disorders | Palpitations | Vascular Disorders | Hypotension | Respiratory, Thoracic, and Mediastinal Disorders | Epistaxis | Oropharyngeal pain | Respiratory disorder | Gastrointestinal Disorders | Abdominal pain upper | Nausea | Constipation | Diarrhoea | Stomatitis | Cheilitis | Vomiting | Melaena | Hepatobiliary Disorders | Hepatic function abnormal | Skin and Subcutaneous Tissue Disorders | Alopecia | Rash | Rash maculo-papular | Dermatitis bullous | Dry skin | Musculoskeletal and Connective Tissue Disorders | Arthralgia | Musculoskeletal pain | Myalgia | Pain in extremity | Renal and Urinary Disorders | Haematuria | Proteinuria | Urinary tract pain | Reproductive System and Breast Disorders | Menorrhagia | General Disorders & Administration Site Conditions | Oedema peripheral | Pyrexia | Investigations | Gamma-glutamyltransferase increased | Alanine aminotransferase increased | Blood alkaline phosphatase increased | Electrocardiogram QT prolonged | Platelet count decreased | Weight decreased | White blood cell count decreased | Aspartate aminotransferase | Aspartate aminotransferase increased | Blood bilirubin increased | Blood lactate dehydrogenase increased | Blood pressure decreased | Lipase increased |
|---|
| Quizartinib 20 mg/Day | 4 | 1 | 1 | 0 | 0 | 4 | 4 | 2 | 1 | 1 | 1 | 0 | 0 | 3 | 3 | 1 | 2 | 1 | 1 | 1 | 0 | 1 | 2 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 2 | 1 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 4 | 3 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 2 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 |
,| Quizartinib 40 mg/Day | 3 | 3 | 1 | 1 | 1 | 3 | 3 | 1 | 0 | 0 | 0 | 1 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 2 | 2 | 1 | 1 | 1 | 3 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 |
Pharmacokinetic Parameter Accumulation Ratio (AR) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The accumulation ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 21 (each cycle 28 days)
| Intervention | accumulation ratio (Geometric Mean) |
|---|
| Cycle 1, Day 21: Quizartinib AR (Cmax) | Cycle 1, Day 21: AC886 AR (Cmax) | Cycle 1, Day 21: Quizartinib + AC886 AR (Cmax) | Cycle 1, Day 21: Quizartinib AR (AUCtau) | Cycle 1, Day 21: AC886 AR (AUCtau) | Cycle 1, Day 21: Quizartinib + AC886 AR (AUCtau) |
|---|
| Quizartinib 20 mg/Day | 1.52 | 2.65 | 2.09 | 2.37 | 3.50 | 2.99 |
,| Quizartinib 40 mg/Day | 1.98 | 2.55 | 2.53 | 2.84 | 3.31 | 3.24 |
Pharmacokinetic Parameter Area Under the Concentration-Time Curve During Dosing Interval of Quizartinib and Metabolite (AC886) After Daily Dose of 20 mg or 40 mg With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
The area under the plasma concentration-time curve during dosing interval (AUCtau) of geometric means is reported at Induction phase Cycle 1, Day 9 and the area under the plasma concentration-time curve during dosing interval at steady state (AUCtauss) of geometric means are reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Cycle 1, Day 8: Quizartinib, AUCtau | Cycle 1, Day 8: AC886, AUCtau | Cycle 1, Day 8: Quizartinib + AC886, AUCtau | Cycle 1, Day 21: Quizartinib, AUCtau,ss | Cycle 1, Day 21: AC886, AUCtau, ss | Cycle 1, Day 21: Quizartinib + AC886, AUCtau |
|---|
| Quizartinib 20 mg/Day | 418 | 555 | 1010 | 991 | 1940 | 3020 |
,| Quizartinib 40 mg/Day | 921 | 1640 | 2640 | 2940 | 5310 | 8850 |
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of Geometric Means of Quizartinib and Active Metabolite (AC886) After Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
The maximum serum plasma concentration (Cmax) is reported at Induction phase Cycle 1, Day 9 and the maximum serum plasma concentration at steady state (Cmax,ss) is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1, Day 8: Quizartinib, Cmax | Cycle 1, Day 8: AC886, Cmax | Cycle 1, Day 8: Quizartinib + AC886, Cmax | Cycle 1, Day 21: Quizartinib, Cmax, ss | Cycle 1, Day 21: AC886, Cmax, ss | Cycle 1, Day 21: Quizartinib + AC886, Cmax |
|---|
| Quizartinib 20 mg/Day | 42.4 | 36.5 | 77.4 | 64.2 | 96.7 | 162 |
,| Quizartinib 40 mg/Day | 91.3 | 103 | 180 | 212 | 256 | 480 |
Pharmacokinetic Parameter Metabolite to Parent Ratio (MR) of Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The metabolite to parent ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 9 for active metabolite AC886 is reported. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 8 (each cycle 28 days)
| Intervention | metabolite to parent ratio (Geometric Mean) |
|---|
| Cycle 1, Day 8: MR (Cmax) | Cycle 1, Day 8: MR (AUCtau) |
|---|
| Quizartinib 20 mg/Day | 0.861 | 1.33 |
,| Quizartinib 40 mg/Day | 1.13 | 1.78 |
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The time of maximum plasma concentration (Tmax) of geometric means is reported at Induction phase Cycle 1, Day 9 and the time of maximum plasma concentration at steady state (Tmax,ss) of geometric means is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
| Intervention | hour (Median) |
|---|
| Cycle 1, Day 8: Quizartinib, Tmax | Cycle 1, Day 8: AC886, Tmax | Cycle 1, Day 8: Quizartinib + AC886, Tmax | Cycle 1, Day 21: Quizartinib, Tmax,ss | Cycle 1, Day 21: AC886, Tmax,ss | Cycle 1, Day 21: Quizartinib + AC886, Tmax |
|---|
| Quizartinib 20 mg/Day | 3.03 | 5.01 | 4.01 | 4.03 | 5.02 | 4.03 |
,| Quizartinib 40 mg/Day | 2.17 | 6.08 | 4.17 | 4.08 | 6.09 | 4.08 |
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
The trough plasma concentration (Ctrough) of geometric means is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886. (NCT02834390)
Timeframe: Induction phase Cycle 1, Day 21 (each cycle 28 days)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1, Day 21: Quizartinib | Cycle 1, Day 21: AC886 | Cycle 1, Day 21: Quizartinib + AC886 |
|---|
| Quizartinib 20 mg/Day | 22.7 | 68.6 | 94.6 |
,| Quizartinib 40 mg/Day | 77.1 | 195 | 299 |
Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. (NCT02834390)
Timeframe: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
| Intervention | percentage of participants (Number) |
|---|
| Composite CR rate (CRc rate: CR+CRp+CRi) | Response rate (CRc+PR) |
|---|
| Quizartinib 20 mg/Day | 75.0 | 100 |
,| Quizartinib 40 mg/Day | 66.7 | 66.7 |
Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. (NCT02834390)
Timeframe: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Complete remission (CR) | CR with incomplete platelet recovery (CRp) | CR with incomplete hematological recovery (CRi) | Partial remission (PR) | No response (NR) |
|---|
| Quizartinib 20 mg/Day | 0 | 0 | 3 | 1 | 0 |
,| Quizartinib 40 mg/Day | 0 | 0 | 2 | 0 | 1 |
Duration of Remission Following CR (DOR) in TP53 WT Population
"DOR is defined for patients achieving complete remission and is the time from clinical remission until relapse or death from any cause, whichever occurs first. For patients with none of these events before time of analysis, DOR is censored at the date of the patient's last response assessment.~The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study." (NCT02545283)
Timeframe: From achieving CR until relapse or death from any cause (up to approximately 4.5 years)
| Intervention | Months (Median) |
|---|
| Placebo Plus Cytarabine | 18.73 |
| Idasanutlin Plus Cytarabine | 16.76 |
Event-Free Survival (EFS) According to HMRA in TP53 WT Population
"Event Free Survival (EFS) is defined as the time from the date of randomization to whichever occurs first: treatment failure (failure to achieve CR, set as day of final response assessment), relapse from CR, or death from any cause. The study was terminated because of futility, therefore did not reach the planned end of the study.~The design followed a hierarchical statistical testing framework." (NCT02545283)
Timeframe: From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)
| Intervention | Weeks (Median) |
|---|
| Placebo Plus Cytarabine | 6.29 |
| Idasanutlin Plus Cytarabine | 4.36 |
Number of Participants Who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03)
Participants who experienced at least one Adverse Event by severity, According to National Cancer Institute common terminology criteria for Adverse Events, version 4.03 (NCI-CTCAE v4.03) have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study. (NCT02545283)
Timeframe: Baseline up to approximately 4.5 years
| Intervention | Participants (Number) |
|---|
| Placebo Plus Cytarabine | 149 |
| Idasanutlin Plus Cytarabine | 232 |
Number of Participants With Adverse Events Leading to Death up to Day 30
The number of participants with AE resulted by death within 30 days from dosing is reported (NCT02545283)
Timeframe: Up to Day 30
| Intervention | Participants (Number) |
|---|
| Placebo Plus Cytarabine | 9 |
| Idasanutlin Plus Cytarabine | 23 |
Number of Participants With Adverse Events Leading to Death up to Day 60
The number of participants with AE resulted by death within 60 days from dosing is reported (NCT02545283)
Timeframe: Up to Day 60
| Intervention | Participants (Number) |
|---|
| Placebo Plus Cytarabine | 24 |
| Idasanutlin Plus Cytarabine | 60 |
Number of Participants With Adverse Events Leading to Discontinuation
Participants with Adverse Events leading to discontinuation of the study have been reported. The study was terminated because of futility, therefore did not reach the planned end of the study. (NCT02545283)
Timeframe: Baseline up to approximately 4.5 years
| Intervention | Participants (Number) |
|---|
| Placebo Plus Cytarabine | 0 |
| Idasanutlin Plus Cytarabine | 0 |
Number of Treatment Cycles Started
Participants who started the study treatment cycles are reported. (NCT02545283)
Timeframe: Up to 3 cycles (1 cycle is 28 days)
| Intervention | Treatment Cycles (Mean) |
|---|
| Placebo Plus Cytarabine | 1.3 |
| Idasanutlin Plus Cytarabine | 1.2 |
Overall Survival in TP53 WT Population
"P53 tumor protein Wild Type (TP53 WT) population's Overall Survival was compared in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo.~The study was terminated because of futility, therefore did not reach the planned end of the study." (NCT02545283)
Timeframe: From randomization to death from any cause (up to approximately 4.5 years)
| Intervention | Months (Median) |
|---|
| Placebo Plus Cytarabine | 9.13 |
| Idasanutlin Plus Cytarabine | 8.28 |
Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population
"Rate of complete response at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo.~The design followed a hierarchical statistical testing framework." (NCT02545283)
Timeframe: At the end of induction (up to Day 56)
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo Plus Cytarabine | 20.3 |
| Idasanutlin Plus Cytarabine | 17.1 |
Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population
Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study. (NCT02545283)
Timeframe: Baseline up to approximately 4.5 years
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo Plus Cytarabine | 10.6 |
| Idasanutlin Plus Cytarabine | 11.6 |
Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population
"Rate of overall remission (complete remission, complete remission with incomplete hematologic recovery, complete remission with incomplete platelet count recovery) at the end of induction in the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo.~The design followed a hierarchical statistical testing framework." (NCT02545283)
Timeframe: At the end of induction (up to Day 56)
| Intervention | Percentage of Participants (Number) |
|---|
| Placebo Plus Cytarabine | 38.8 |
| Idasanutlin Plus Cytarabine | 22.0 |
Total Duration of Study Treatment
Participants were planned to be treated up to 3 Cycles. (NCT02545283)
Timeframe: Up to 3 cycles (1 cycle is 28 days)
| Intervention | Days (Mean) |
|---|
| Idasanutlin Plus Cytarabine | 16.5 |
| Placebo Plus Cytarabine | 17.6 |
Change From Baseline in Body Temperature Over Time
"Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)
| Intervention | C, Celsius Degree (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 1 Day 22 | Cycle 1 Day 28 | Cycle 1 Day 29-42 | Cycle 1 Day 43-56 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 2 Day 22 | Cycle 2 Day 28 | Cycle 2 Day 29-56 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 3 Day 15 | Cycle 3 Day 22 | Cycle 3 Day 28 | Cycle 3 Day 29-56 |
|---|
| Idasanutlin Plus Cytarabine | 36.52 | 0.32 | 0.46 | 0.36 | 0.23 | 0.00 | 0.07 | -0.10 | 0.07 | 0.34 | 0.10 | 0.04 | -0.09 | -0.19 | -0.04 | 0.29 | 0.04 | -0.15 | -0.25 |
,| Placebo Plus Cytarabine | 36.49 | 0.07 | 0.30 | 0.22 | 0.06 | 0.08 | -0.02 | 0.11 | -0.08 | 0.17 | 0.04 | -0.22 | -0.06 | -0.25 | 0.10 | -0.09 | -0.07 | -0.26 | 0.27 |
Change From Baseline in Diastolic Blood Pressure Over Time
"Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 1 Day 22 | Cycle 1 Day 28 | Cycle 1 Day 29-42 | Cycle 1 Day 43-56 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 2 Day 22 | Cycle 2 Day 28 | Cycle 2 Day 29-56 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 3 Day 15 | Cycle 3 Day 22 | Cycle 3 Day 28 | Cycle 3 Day 29-56 |
|---|
| Idasanutlin Plus Cytarabine | 71.5 | -3.1 | -1.3 | -1.4 | -0.7 | 0.6 | 0.9 | 0.9 | -2.2 | -1.5 | 1.7 | 3.9 | 3.2 | 0.3 | -3.3 | -1.8 | -2.1 | 1.3 | 2.6 |
,| Placebo Plus Cytarabine | 70.2 | -1.5 | -1.3 | -0.5 | 1.0 | 3.8 | 1.7 | 1.1 | 0.4 | -0.6 | 3.1 | 4.6 | -2.9 | 5.0 | 2.0 | 0.7 | 10.1 | 2.3 | 5.0 |
Change From Baseline in Electrocardiogram Parameters: PQ, PR, RR, QRS, QT and QTcF Intervals
"Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline, Days 1, 2, and 5 of Cycle 1, Days 1, 2 of Cycles 2 and 3 (1 cycle is 28 days), Treatment Discontinuation Visit (28 days after last dose of study drug)
| Intervention | Millisecond (msec) (Mean) |
|---|
| PR Duration Baseline | PR Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | PR Duration Cycle 1 Day 1 - Post-Cytarabine | PR Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | PR Duration Cycle 1 Day 2 | PR Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | PR Duration Cycle 1 Day 5 Post-Cytarabine | PR Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | PR Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | PR Duration Cycle 2 Day 1 Post-Cytarabine | PR Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | PR Duration Cycle 2 Day 2 | PR Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | PR Duration Cycle 3 Day 1 Post-Cytarabine | PR Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | PR Duration Cycle 3 Day 2 | PR Duration Study Drug Completion/Discontinuation | QRS Duration Baseline | QRS Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QRS Duration Cycle 1 Day 1 Post-Cytarabine | QRS Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | QRS Duration Cycle 1 Day 2 | QRS Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | QRS Duration Cycle 1 Day 5 Post-Cytarabine | QRS Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | QRS Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QRS Duration Cycle 2 Day 1 Post-Cytarabine | QRS Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | QRS Duration Cycle 2 Day 2 | QRS Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QRS Duration Cycle 3 Day 1 Post-Cytarabine | QRS Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | QRS Duration Cycle 3 Day 2 | QRS Duration Study Drug Completion/Discontinuation | QT Duration Baseline | QT Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QT Duration Cycle 1 Day 1 Post-Cytarabine | QT Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | QT Duration Cycle 1 Day 2 | QT Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | QT Duration Cycle 1 Day 5 Post-Cytarabine | QT Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | QT Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QT Duration Cycle 2 Day 1 Post-Cytarabine | QT Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | QT Duration Cycle 2 Day 2 | QT Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QT Duration Cycle 3 Day 1 Post-Cytarabine | QT Duration Cycle 3 Day 1 - 6 Hours Post-Idasanutlin/Placebo | QT Duration Cycle 3 Day 2 | QT Duration Study Drug Completion/Discontinuation | QTcB Baseline | QTcB Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QTcB Cycle 1 Day 1 Post-Cytarabin | QTcB Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcB Cycle 1 Day 2 | QTcB Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placeb | QTcB Cycle 1 Day 5 Post-Cytarabine | QTcB Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | QTcB Cycle 2 Day 1 - Within 2 Hours Pre-Idasanutlin/Placebo | QTcB Cycle 2 Day 1 Post-Cytarabine | QTcB Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcB Cycle 2 Day 2 | QTcB Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QTcB Cycle 3 Day 1 Post-Cytarabine | QTcB Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcB Cycle 3 Day 2 | QTcB Study Drug Completion/Discontinuation | QTcF Baseline | QTcF Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QTcF Cycle 1 Day 1 Post-Cytarabine | QTcF Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcF Cycle 1 Day 2 | QTcF Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | QTcF Cycle 1 Day 5 Post-Cytarabine | QTcF Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | QTcF Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QTcF Cycle 2 Day 1 Post-Cytarabine | QTcF Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcF Cycle 2 Day 2 | QTcF Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | QTcF Cycle 3 Day 1 - Post-Cytarabine | QTcF Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | QTcF Cycle 3 Day 2 | QTcF Study Drug Completion/Discontinuation | RR Duration Baseline | RR Duration Cycle 1 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | RR Duration Cycle 1 Day 1 Post-Cytarabine | RR Duration Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | RR Duration Cycle 1 Day 2 | RR Duration Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | RR Duration Cycle 1 Day 5 Post-Cytarabine | RR Duration Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | RR Duration Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | RR Duration Cycle 2 Day 1 Post-Cytarabine | RR Duration Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | RR Duration Cycle 2 Day 2 | RR Duration Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | RR Duration Cycle 3 Day 1 Post-Cytarabine | RR Duration Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | RR Duration Cycle 3 Day 2 | RR Duration Study Drug Completion/Discontinuation |
|---|
| Idasanutlin Plus Cytarabine | 155.5 | -2.7 | 1.6 | 1.6 | 1.4 | -2.1 | -1.6 | -3.5 | 2.2 | 4.9 | 6.0 | 5.9 | 6.7 | 3.9 | 6.9 | 14.1 | -7.7 | 89.3 | -1.9 | -1.0 | -1.1 | 1.1 | 1.6 | 0.2 | -0.3 | 0.4 | -2.1 | 0.1 | 0.2 | -2.4 | -2.0 | -2.7 | -1.6 | -0.4 | 385.6 | 4.2 | 4.4 | 0.0 | 3.1 | 1.6 | 4.7 | 3.4 | 8.5 | 10.6 | 4.1 | 9.9 | 15.9 | 22.0 | 19.0 | 28.0 | -4.8 | 437.5 | 4.8 | 3.8 | 6.4 | 2.4 | -3.2 | -3.7 | -5.5 | 1.6 | 4.2 | 4.6 | -1.0 | -1.1 | 13.6 | 21.9 | 14.3 | 5.8 | 419.0 | 5.1 | 4.1 | 4.2 | 2.6 | -1.1 | -0.4 | -2.1 | 4.0 | 6.4 | 4.0 | 1.1 | 14.0 | 16.8 | 20.7 | 19.2 | 2.9 | 787.9 | 4.8 | 3.6 | -19.1 | 4.1 | 19.5 | 36.8 | 37.8 | 25.7 | 23.3 | -15.2 | 14.1 | 65.5 | 38.9 | 3.3 | 62.0 | -14.8 |
,| Placebo Plus Cytarabine | 160.3 | 12.4 | 4.8 | 0.6 | 2.1 | -3.0 | 1.2 | -5.7 | 30.0 | -4.2 | -3.0 | -3.0 | 9.3 | -7.7 | -4.5 | -1.0 | -5.3 | 92.8 | -0.4 | -0.9 | -0.6 | -0.5 | 1.1 | 0.6 | 0.3 | 0.8 | 6.5 | 2.0 | 0.3 | -0.1 | 2.7 | 0.4 | 1.5 | -1.3 | 388.7 | 6.0 | 0.7 | 1.1 | 5.4 | 24.8 | 25.0 | 27.8 | -9.1 | -11.5 | -7.5 | 12.2 | 1.9 | 21.2 | -3.4 | -9.4 | -5.6 | 435.3 | 8.7 | 1.3 | 1.4 | -1.8 | -8.3 | -4.4 | -5.2 | 0.5 | 3.0 | 6.5 | 0.8 | 13.1 | 16.6 | 6.9 | 1.4 | 1.9 | 418.0 | 7.6 | 1.0 | 0.9 | 1.3 | 3.6 | 6.1 | 6.0 | 0.0 | 0.5 | 1.5 | 6.1 | 14.0 | 18.5 | 3.5 | -2.6 | 0.2 | 797.9 | -2.5 | -4.7 | -3.0 | 37.6 | 159.3 | 133.7 | 144.2 | -5.4 | -38.8 | -66.9 | 57.9 | 15.1 | 11.1 | -49.4 | -42.9 | -14.8 |
Change From Baseline in Heart Rate, as Measured by Electrocardiogram
"Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline; Cycles 1-3 Day 1 (2 hrs pre-dose, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo ); Cycle 1-3 Day 2; Cycle 1 Day 5 (within 2 hrs Idanasanutlin/Placebo, post-Cytarabine and 6 hrs post-Idasanutlin/Placebo), Study Drug Completion
| Intervention | Beats per Minute (Mean) |
|---|
| Baseline | Cycle 1 Day 1 2 Hours Pre-dose | Cycle 1 Day 1 Post-Cytarabine | Cycle 1 Day 1 6 Hours Post-Idasanutlin/Placebo | Cycle 1 Day 2 | Cycle 1 Day 5 Within 2 Hours Pre-Idasanutlin/Placebo | Cycle 1 Day 5 - Post-Cytarabine | Cycle 1 Day 5 6 Hours Post-Idasanutlin/Placebo | Cycle 2 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | Cycle 2 Day 1 Post-Cytarabine | Cycle 2 Day 1 6 Hours Post-Idasanutlin/Placebo | Cycle 2 Day 2 | Cycle 3 Day 1 Within 2 Hours Pre-Idasanutlin/Placebo | Cycle 3 Day 1 Post-Cytarabine | Cycle 3 Day 1 6 Hours Post-Idasanutlin/Placebo | Cycle 3 Day 2 | Study Drug Completion/Discontinuation |
|---|
| Idasanutlin Plus Cytarabine | 78.6 | -0.8 | -0.4 | 1.4 | -0.4 | -1.2 | -3.0 | -3.1 | -4.8 | -4.8 | -0.7 | -4.8 | -7.1 | -4.5 | -0.1 | -9.3 | 4.5 |
,| Placebo Plus Cytarabine | 77.3 | 1.1 | -0.1 | 0.1 | -2.2 | -10.3 | -9.9 | -10.7 | -0.5 | 0.8 | -0.7 | -5.2 | -3.0 | -8.9 | -2.0 | 0.1 | 3.4 |
Change From Baseline in Pulse Rate Over Time
"Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)
| Intervention | Beats per Minute (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 1 Day 22 | Cycle 1 Day 28 | Cycle 1 Day 29-42 | Cycle 1 Day 43-56 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 2 Day 22 | Cycle 2 Day 28 | Cycle 2 Day 29-56 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 3 Day 15 | Cycle 3 Day 22 | Cycle 3 Day 28 | Cycle 3 Day 29-56 |
|---|
| Idasanutlin Plus Cytarabine | 79.2 | 3.4 | 1.1 | 4.1 | 4.0 | 5.1 | 6.8 | -0.9 | 2.4 | 1.7 | 0.3 | 1.2 | 4.0 | 1.0 | 2.4 | 1.9 | 3.4 | 0.9 | 5.2 |
,| Placebo Plus Cytarabine | 78.4 | -4.3 | 1.5 | 0.2 | 4.8 | 2.0 | 5.5 | 2.0 | -3.3 | -0.4 | 2.3 | -2.3 | 1.8 | 0.4 | 1.3 | 2.5 | 4.8 | 0.4 | -5.0 |
Change From Baseline in Respiratory Rate Over Time
"Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Up to Approximately 4.5 Years
| Intervention | Breaths per Minute (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 1 Day 22 | Cycle 1 Day 28 | Cycle 1 Day 29-42 | Cycle 1 Day 43-56 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 2 Day 22 | Cycle 2 Day 28 | Cycle 2 Day 29-56 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 3 Day 15 | Cycle 3 Day 22 | Cycle 3 Day 28 | Cycle 3 Day 29-56 |
|---|
| Idasanutlin Plus Cytarabine | 16.6 | 0.0 | 0.4 | 0.7 | 0.6 | 0.5 | 0.0 | -0.2 | 0.1 | 0.0 | 0.4 | 0.5 | 0.3 | 0.2 | -1.0 | 0.9 | 0.8 | 0.8 | 0.1 |
,| Placebo Plus Cytarabine | 16.3 | -0.1 | 0.7 | 0.6 | 0.4 | 0.7 | 0.3 | -0.3 | -0.2 | 0.5 | 0.8 | -0.3 | 0.2 | 1.1 | 0.2 | 1.5 | 1.1 | 0.3 | 0.7 |
Change From Baseline in Systolic Blood Pressure Over Time
"Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.~The study was terminated because of futility, therefore did not reach the planned end of study." (NCT02545283)
Timeframe: Baseline; Cycles 1-3, Days 8, 15, 22, 28 (1 cycle is 28 days); and, if incomplete blood count recovery, Days 29-42 and Days 43-56, Cycles 2 -3 Days 1, 8, 15, 22, 28 and 29-56 (max delay between cycles is 56 days)
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 1 Day 22 | Cycle 1 Day 28 | Cycle 1 Day 29-42 | Cycle 1 Day 43-56 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 2 Day 22 | Cycle 2 Day 28 | Cycle 2 Day 29-56 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 3 Day 15 | Cycle 3 Day 22 | Cycle 3 Day 28 | Cycle 3 Day 29-56 |
|---|
| Idasanutlin Plus Cytarabine | 122.1 | -6.9 | -0.1 | -1.5 | -0.5 | 3.4 | 3.8 | 0.6 | -5.1 | -0.2 | 2.5 | 5.0 | 6.6 | 2.3 | -1.7 | 0.2 | -1.1 | 7.1 | 5.1 |
,| Placebo Plus Cytarabine | 120.6 | -3.7 | -2.8 | 0.7 | 1.2 | 4.4 | 9.8 | 6.9 | 5.3 | -1.7 | 5.5 | 5.8 | -1.0 | 11.2 | 6.0 | 3.3 | 13.9 | 5.3 | 27.7 |
Cumulative Dose of Idasanutlin and Cytarabine
The cumulative doses of idasanutlin and cytaradine are reported. (NCT02545283)
Timeframe: Up to 3 cycles (1 cycle is 28 days)
| Intervention | Milligram (mg) (Mean) |
|---|
| Cytarabine cumulative dose (mg) |
|---|
| Placebo Plus Cytarabine | 11500 |
Cumulative Dose of Idasanutlin and Cytarabine
The cumulative doses of idasanutlin and cytaradine are reported. (NCT02545283)
Timeframe: Up to 3 cycles (1 cycle is 28 days)
| Intervention | Milligram (mg) (Mean) |
|---|
| Idasanutlin/Placebo cumulative dose (mg) | Cytarabine cumulative dose (mg) |
|---|
| Idasanutlin Plus Cytarabine | 3340.1 | 11200 |
Number of Participants With Clinical Laboratory Abnormalities in Biochemistry Tests at the Greatest Severity, According to NCI-CTCAE v4.03
"Laboratory parameters for blood biochemistry will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment.~For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality." (NCT02545283)
Timeframe: Up to Approximately 4.5 Years
| Intervention | Participants (Number) |
|---|
| Albumin Low | Alkaline Phosphatase High | SGPT/ALT High | SGOT/AST High | Calcium Low | Creatinine High | Glucose Low | Glucose High | Magnesium Low | Magnesium High | Phosphorus Low | Potassium High | Sodium Low | Sodium High | Bilirubin High | Uric Acid High | Potassium Low |
|---|
| Idasanutlin Plus Cytarabine | 22 | 9 | 16 | 13 | 36 | 11 | 0 | 25 | 8 | 10 | 72 | 8 | 17 | 7 | 42 | 53 | 76 |
,| Placebo Plus Cytarabine | 8 | 2 | 13 | 9 | 8 | 4 | 1 | 9 | 0 | 5 | 18 | 5 | 6 | 1 | 9 | 29 | 21 |
Number of Participants With Clinical Laboratory Abnormalities in Hematology Tests at the Greatest Severity, According to NCI-CTCAE v4.03
"Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside the standard reference range are considered abnormalities. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment or a medical intervention; or is clinically significant in the investigator's judgment.~For each patient, baseline is the last observation prior to initiation of study drug. For each laboratory test, patients with at least 1 post-baseline assessment are included in the analysis. For each cell, the denominator is the number of patients with baseline NCI-CTCAE Grade 0-2 in the specified direction of abnormality, or Grade 1-4 in the opposite direction of abnormality." (NCT02545283)
Timeframe: Up to Approximately 4.5 Years
| Intervention | Participants (Number) |
|---|
| Hemoglobin Low | Hemoglobin High | Lymphocytes Abs Low | Lymphocytes Abs High | Neutrophils, Total, Abs Low | Platelet Low | Total Leukocyte Count Low | Total Leukocyte Count High |
|---|
| Idasanutlin Plus Cytarabine | 191 | 1 | 229 | 1 | 97 | 128 | 184 | 1 |
,| Placebo Plus Cytarabine | 83 | 1 | 109 | 1 | 40 | 59 | 87 | 1 |
Overall Survival in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
Overall survival in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2 respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The Median upper limits were set to 999 because they were not reached and therefore it was Not Evaluable (NE) and the field is numeric only. The study was terminated because of futility, therefore did not reach the planned end of the study. (NCT02545283)
Timeframe: From randomization to death from any cause (up to approximately 4.5 years)
| Intervention | Months (Median) |
|---|
| IDH2 | IDH1 | FLT3 |
|---|
| Idasanutlin Plus Cytarabine | 11.01 | 8.25 | 5.55 |
,| Placebo Plus Cytarabine | 11.37 | 9.13 | 4.76 |
Percentage of Participants With Complete Response (CR) in Clinically Actionable Mutation-Defined Subpopulation (FLT3, IDH1 and IDH2) in TP53 WT Population
Rate of complete response at the end of induction in mutation-defined subgroups (positive for mutation of FLT3, IDH1 and IDH2, respectively) of the TP53 WT population was compared in participants who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. (NCT02545283)
Timeframe: At the end of induction (up to Day 56)
| Intervention | Percentage of Participants (Number) |
|---|
| FLT3 | IDH1 | IDH2 |
|---|
| Idasanutlin Plus Cytarabine | 15.3 | 34.8 | 29.5 |
,| Placebo Plus Cytarabine | 12.5 | 11.1 | 23.1 |
Disease-free Survival (DFS) for Patients Who Are MRD Negative
Disease-free survival for patients who are MRD negative but lack high or low risk molecular and cytogenetic features, defined as time from end of first course of therapy to death or relapse (NCT04326439)
Timeframe: Up to 2 years post-intervention
| Intervention | years (Median) |
|---|
| Patients Who Are MRD Negative | 1.08 |
Event-free Survival (EFS) in Low Risk Patients and High Risk Patients
Event-free survival defined as the time from on study to death, failure to achieve remission or relapse in newly diagnosed patients with pediatric acute myeloid leukemia in the Low risk stratification group and High risk stratification group (NCT04326439)
Timeframe: Up to 2 years post-intervention
| Intervention | years (Median) |
|---|
| Aflac-AML Low Risk Patients | 1.20 |
| Aflac-AML High Risk Patients | 0.76 |
Minimal Residual Disease (MRD) Negative Status
Number of patients that are in remission (MRD negative) after course 1 in participants receiving GO and those that did not receive GO. (NCT04326439)
Timeframe: Post-induction I, an average of 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Induction I With GO | 5 |
| Induction I Without GO | 3 |
Overall Survival (OS)
Time from study entry and from end of first course of therapy for newly diagnosed patients with pediatric acute myeloid leukemia (NCT04326439)
Timeframe: Up to 2 years post-intervention
| Intervention | years (Median) |
|---|
| Aflac-AML Low Risk Patients | 1.97 |
| Aflac-AML High Risk Patients | 1.98 |
Cardiotoxicity in Patients With de Novo AML That Receive the Four-cycle Aflac-AML Regimen With the Inclusion of Dexrazoxane
Number of patients that develop cardiac ejection fraction <50% (CTCAE V5.0 grade 2 or greater dysfunction) either during therapy (early cardiotoxicity) or after completion of therapy (late cardiotoxicity) (NCT04326439)
Timeframe: At completion of Cycle 4 (each cycle average is 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Early cardiotoxicity | Late cardiotoxicity |
|---|
| Aflac-AML High Risk Patients | 0 | 0 |
,| Aflac-AML Low Risk Patients | 0 | 0 |
Duration of Hospital Admission in Patients That Developed Infection and Febrile Neutropenia at the End of Each Treatment Cycle
Duration of hospital admission in patients that developed infection and febrile neutropenia at the end of each treatment cycle (NCT04326439)
Timeframe: At the end of each cycle (each cycle average is 28 days)
| Intervention | days (Mean) |
|---|
| Cycle 1 - Induction 1 | Cycle 2 - Induction 2 |
|---|
| Aflac-AML High Risk Patients | 30 | 30.0 |
Duration of Hospital Admission in Patients That Developed Infection and Febrile Neutropenia at the End of Each Treatment Cycle
Duration of hospital admission in patients that developed infection and febrile neutropenia at the end of each treatment cycle (NCT04326439)
Timeframe: At the end of each cycle (each cycle average is 28 days)
| Intervention | days (Mean) |
|---|
| Cycle 1 - Induction 1 | Cycle 2 - Induction 2 | Cycle 3 - Induction 3 | Cycle 4 - Induction 4 |
|---|
| Aflac-AML Low Risk Patients | 33 | 29.3 | 29 | 27.5 |
Proportion of Patients Who Develop Infection and/or Febrile Neutropenia During Each Treatment Course
Number of participants that developed infection and/or febrile neutropenia at the end of each treatment cycle. (NCT04326439)
Timeframe: At the end of each cycle (each cycle average is 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 - Induction 1 | Cycle 2 - Induction 2 | Cycle 3 - Induction 3 | Cycle 4 - Induction 4 |
|---|
| Aflac-AML High Risk Patients | 2 | 2 | 0 | 0 |
,| Aflac-AML Low Risk Patients | 5 | 3 | 2 | 2 |
Duration of Event-Free Survival (EFS)
"EFS was defined as the time from the date of randomization until the date of documented relapse (excluding relapse after PR), treatment failure or death from any cause within 30 days after the last dose of study drug, whichever occurred first (earliest of [relapse date, treatment failure date, death date] - randomization date + 1). If a participant experienced relapse or death within 30 days after the last dose of study drug, the participant was defined as having an EFS event related to either relapse or death, and the event date was the date of relapse or death. For a participant who was not known to have had a relapse or treatment failure or death event, EFS was censored at the date of last relapse-free disease assessment (last relapse-free disease assessment date - randomization date + 1). Data was estimated based on Kaplan-Meier estimates." (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Months (Median) |
|---|
| Gilteritinib | 2.8 |
| Salvage Chemotherapy | 0.7 |
Duration of Leukemia-Free Survival (LFS)
The LFS was defined as the time from the date of first CRc until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CRc (relapse date or death date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1). For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc disease assessment date + 1). (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Months (Median) |
|---|
| Gilteritinib | 4.4 |
| Salvage Chemotherapy | 6.7 |
Duration of Overall Survival (OS)
Overall survival was defined as the time from the date of randomization until the date of death from any cause (death date - randomization date + 1). For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact (date of last contact - randomized date + 1). The date of last contact was the latest date that the participant was known to be alive by the cutoff date. The last contact date was derived for participants alive at the analysis cutoff date. Survival rate and 95% CI were estimated using the Kaplan-Meier method and the Greenwood formula. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Months (Median) |
|---|
| Gilteritinib | 9.3 |
| Salvage Chemotherapy | 5.6 |
Duration of Remission
Duration of remission included duration of composite complete remission (CRc), duration of complete remission (CR)/ complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR and duration of response (CRc + partial remission (PR). The duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse (i.e., the date of first NR after CRc or PR) for participants who achieved CRc or PR (relapse date - first CRc or PR disease assessment date + 1). Participants who died without report of relapse were considered nonevents and censored at their last relapse-free disease assessment date (last relapse-free disease assessment date - first CRc or PR disease assessment date + 1). Other participants who did not relapse during the study were considered nonevents and censored at the last relapse-free assessment date. Duration of CR was only applicable to participants with best overall response of CR. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Months (Median) |
|---|
| Gilteritinib | 14.8 |
| Salvage Chemotherapy | 1.8 |
Percentage of Participants Who Underwent Hematopoietic Stem Cell Transplant
Transplantation rate is defined as the percentage of participants undergoing Hematopoietic stem cell transplant (HSCT) during the study period. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Percentage of participants (Number) |
|---|
| Gilteritinib | 25.5 |
| Salvage Chemotherapy | 15.3 |
Percentage of Participants With Complete Remission (CR) Rate
The CR rate was defined as the number of participants who achieved the best response of CR divided by the number of participants in the analysis population. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, all participants included in the primary analysis of CR rate were followed up at least 6 months
| Intervention | Percentage of participants (Number) |
|---|
| Gilteritinib | 21.1 |
| Salvage Chemotherapy | 10.5 |
Percentage of Participants With Complete Remission (CR) With Partial Hematological Recovery (CRh)
CRh rate was defined as the number of participants who achieved CRh at any of the postbaseline visits and did not have a best response of CR divided by the number of participants in the analysis population. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Percentage of participants (Number) |
|---|
| Gilteritinib | 34.0 |
| Salvage Chemotherapy | 15.3 |
Percentage of Participants With Composite Complete Remission (CRc Rate)
CRc rate was defined as the number of participants who achieved the best response of CRc (CR,complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi) divided by the number of participants in the analysis population. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median time of follow-up for OS was 17.8 months
| Intervention | Percentage of participants (Number) |
|---|
| Gilteritinib | 54.3 |
| Salvage Chemotherapy | 21.8 |
Change From Baseline in Brief Fatigue Inventory (BFI)
The Brief Fatigue Inventory (BFI) is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A global fatigue score can be obtained by averaging all the items on the BFI. The global BFI score will be calculated only if at least 5 of the 9 items are answered. A higher BFI fatigue score indicates worse outcome. (NCT02421939)
Timeframe: Baseline and cycle 1, day 8 and cycle 2 day 1 (up to data cut off date of 17 Sep 2018)
| Intervention | Units on a scale (Mean) |
|---|
| Cycle 1 day 8 (C1D8) | Cycle 2 day 1 (C2D1) |
|---|
| Gilteritinib | -0.4 | 0.0 |
,| Salvage Chemotherapy | 1.0 | 0.4 |
Number of Participants With Adverse Events
"A treatment-emergent adverse event (TEAE) was defined as an AE observed after starting administration of the study drug (gilteritinib or salvage chemotherapy). If the AE occurred on day 1 and the onset check box was marked Onset after first dose of study drug or the onset check box was left blank, then the AE was considered treatment emergent. If the AE occurred on day 1 and the onset check box was marked Onset before first dose of study drug, then the AE was not considered treatment emergent. Majority of salvage chemotherapy participants finished the study by cycle 2 of treatment, the duration of exposure was longer in the gilteritinib arm compared with the salvage chemotherapy arm (126.00 [4.0, 885.0] days versus 28.0 [5.0, 217.0] days). The NCI-CTCAE is defined as National Cancer Institute-Common Terminology Criteria for Adverse Events." (NCT02421939)
Timeframe: From first dose of study drug up to 30 days after the last dose of study drug (median treatment duration for gilteritinib was (126.00 [4.0, 885.0]) days versus salvage chemotherapy 28.0 [5.0, 217.0] days)
| Intervention | Participants (Count of Participants) |
|---|
| Drug-related TEAE | Serious TEAE | Drug-related serious TEAE | TEAE leading to death | Drug-related TEAE leading to death | TEAE leading to withdrawal of treatment | Drug-related TEAE lead withdrawal of treatment | NCI-CTCAE Grade 3 or higher TEAE | Drug-related Grade 3 or higher TEAE | Death |
|---|
| Gilteritinib | 206 | 205 | 88 | 71 | 10 | 58 | 27 | 236 | 153 | 170 |
,| Salvage Chemotherapy | 71 | 34 | 16 | 16 | 5 | 13 | 5 | 94 | 57 | 81 |
Percentage of Participants Who Achieved Transfusion Conversion and Maintenance
Transfusion conversion & maintenance rate was defined for gilteritinib arm. Participants were classified as transfusion independent if there were no RBC or platelet transfusions within 28 days prior to the first dose to 28 days after the first dose; otherwise they were classified as transfusion dependent at baseline. Participants were considered independent postbaseline if they had 1 consecutive 8 week period without any RBC or platelet transfusion from 29 days after the first dose until the last dose date. For participants who were on treatment ≤ 4 weeks or > 4 weeks but < 12 weeks and there was no RBC or platelet transfusion within postbaseline period, they were considered not evaluable; otherwise, they were considered postbaseline transfusion dependent. Transfusion conversion rate was defined for participants who had evaluable postbaseline transfusion status. Transfusion status (independent vs. dependent) at baseline and postbaseline was reported in a 2 by 2 contingency table. (NCT02421939)
Timeframe: From randomization until the data cut-off date of 17 Sep 2018, median treatment duration for gilteritinib was (126.00 [4.0, 885.0]) days versus salvage chemotherapy 28.0 [5.0, 217.0] days)
| Intervention | Percentage of participants (Number) |
|---|
| Baseline Independent/ Post baseline Independent | Baseline Independent/Post baseline Dependent | Baseline Independent/Post baseline Not Evaluable | Baseline Dependent/Post baseline Independent | Baseline Dependent/Post baseline Dependent | Baseline Dependent/Post baseline Not Evaluable |
|---|
| Gilteritinib | 59.2 | 24.5 | 16.3 | 34.5 | 55.8 | 9.6 |
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh) in the Gilteritinib Arm
The CR/CRh rate was defined as the number of participants who achieved either CR or CRh at any of the postbaseline visits divided by the number of participants in the analysis population. (NCT02421939)
Timeframe: From randomization until the data cut-off date 04 Aug 2017, the 142 patients included in the primary analysis of CR/CRh rate were followed up at least 112 days
| Intervention | Percentage of participants (Number) |
|---|
| CR/CRh rate | CR rate | CRh rate |
|---|
| Gilteritinib | 28.2 | 19.0 | 9.2 |
4 Year Overall Survival Rate
Percentage of patients who were alive at 4 years. The 4-year survival rate was estimated using the Kaplan Meier method. (NCT00098774)
Timeframe: 4 years
| Intervention | percentage of participants (Number) |
|---|
| Intensive Combination Chemo & Immunotherapy | 65 |
4 Year Progression Free Rate
"Percentage of patients who were progression free at 4 years. The 4-year progression free rate was estimated using the Kaplan Meier method.~Relapse was assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Progression required a 25% increase of previous area of gadolinium enhancement, appearance of new areas of T1 gadolinium enhancement or new appearance of malignant cells in the spinal fluid or new tumor appearance in other sites of the body" (NCT00098774)
Timeframe: 4 years
| Intervention | percentage of participants (Number) |
|---|
| Intensive Combination Chemo & Immunotherapy | 48 |
Complete Response Rate After Remission Induction
Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease. (NCT00098774)
Timeframe: 4 months
| Intervention | percentage of participants (Number) |
|---|
| Intensive Combination Chemo & Immunotherapy | 66 |
Change From Baseline in Mini-Mental Status Evaluation at 4 Months
Neurologic functioning will be assessed using the Mini-Mental Status Evaluation (MMSE), a standardized, bedside tool for evaluation of higher mental function. This assessment is based on a 30-point scale (0-30) with higher scores associated with better performance. (NCT00098774)
Timeframe: Baseline & month 4
| Intervention | units on a scale (Median) |
|---|
| Baseline Score | 4 month Score | Change from Baseline |
|---|
| Intensive Combination Chemo & Immunotherapy | 27 | 28 | 1 |
Disease-free Survival (DFS)
Time from end of Intensification I to relapse, death or last contact (NCT00372593)
Timeframe: At 3 years from end of Intensification I
| Intervention | Percentage participants DFS at 3 years (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 56.6 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 63.0 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 75.0 |
Event-free Survival at 3 Years
The Kaplan-Meier method will be used to calculate estimates of Event Free Survival (EFS). The log-rank test will be used to compare survival between treatment groups. Analysis of EFS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to Overall Survival (OS) and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt^2 (truncated at 3 standard deviations) and 2.5% type I error. (NCT00372593)
Timeframe: Time from study entry to time of induction failure, relapse, or death, assessed at 3 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 46.9 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 53.1 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 50.0 |
Mortality
Number of participants who died during the first three courses of therapy. (NCT00372593)
Timeframe: During the first three courses of therapy
| Intervention | Number of participants (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 11 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 13 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 1 |
Overall Survival at 3 Years
The Kaplan-Meier method will be used to calculate estimates of OS. Analysis of OS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to OS and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt^2 (truncated at 3 standard deviations) and 2.5% type I error. (NCT00372593)
Timeframe: Time from study entry, assessed at 3 years
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 65.4 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 69.4 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 50.0 |
Remission Induction Rate After 2 Courses of Induction Therapy
Patients without an evaluable bone marrow at the end of Induction I will be excluded from the calculation of remission rate after 2 courses of therapy because their responses are not evaluable. The following patients will be considered to not be in complete remission (CR) after 2 courses of therapy: (1) patients who die during Induction I and II; (2) patients with ≥ 5% blasts or extramedullary disease at the end of Induction II. (NCT00372593)
Timeframe: After 2 courses of induction (I and II) therapy, assessed for up to 10 years
| Intervention | Proportion of participants (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 0.851324 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 0.882716 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 0.666667 |
Toxicities, Including Infectious Complications
Number of participants with at least one grade 3 or higher adverse event during therapy. (NCT00372593)
Timeframe: From the time therapy is initiated, assessed up to 10 years
| Intervention | Number of participants (Number) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 482 |
| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 477 |
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 5 |
Time to Marrow Recovery
Mean time to ANC recovery - defined as ANC greater than 500/MicroLiter for 3 consecutive days. (NCT00372593)
Timeframe: At 25 days after treatment with Induction I, Induction II, and Intensification I
| Intervention | Mean days (Mean) |
|---|
| During Induction I (days 0 - 28 of therapy) | During Induction II (days 29 - 56 of therapy) | During Intensification I (days 57 - 84 of therapy) |
|---|
| Arm A: Standard Arm - No GMTZ, AML Patients With Down Syndrome | 29.17 | 26.6 | 24.5 |
,| Arm A: Standard Arm - No GMTZ, AML Pts w/Out Down Syndrome | 30.56 | 28.54 | 27.51 |
,| Arm B: Experimental - With GMTZ, AML Pts w/Out Down Syndrome | 30.56 | 28.52 | 28.10 |
Event-free Survival
Monitoring of efficacy results will be performed in comparison with historical results. (NCT00096135)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| CNS Patients - Treatment (Combination Chemotherapy) | 64.9 |
| Testicular Relapse Patients (Combination Chemotherapy) | 70 |
Event-free Survival (EFS)
12-month event free survival (NCT02728050)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| CLAGM+Sorafenib Phase 2 | 81 |
Number of Participants With Adverse Events
Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. (NCT02728050)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1, Dose Level 1 | 6 |
| Phase 1, Dose Level 2 | 6 |
| Phase 1, Dose Level 3 | 11 |
| Phase 1, Dose Level 4 | 8 |
| Phase 1, Dose Level 5 | 9 |
| Phase 1, Dose Level 6 | 7 |
| Phase 2, Dose Level 6 | 32 |
Overall Response Rate (ORR)
ORR, defined as CR+CRi, rates of patients treated with CLAG-M with sorafenib. (NCT02728050)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1, Dose Level 1 | 6 |
| Phase 1, Dose Level 2 | 6 |
| Phase 1, Dose Level 3 | 8 |
| Phase 1, Dose Level 4 | 5 |
| Phase 1, Dose Level 5 | 9 |
| Phase 1, Dose Level 6 | 7 |
| Phase 2, Dose Level 6 | 34 |
Overall Survival (OS)
12-month overall survival (NCT02728050)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| CLAGM+Sorafenib Phase 2 | 86 |
Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Mitoxantrone
MTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is < 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting >48 hours leading to >7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count <500/ µL or platelet count <50,000/µL for >49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if <2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D). (NCT02728050)
Timeframe: First 28 days of treatment
| Intervention | mg/m^2 (Number) |
|---|
| CLAGM+Sorafenib Phase 1 | 18 |
Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Sorafenib
MTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is < 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting >48 hours leading to >7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count <500/ µL or platelet count <50,000/µL for >49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if <2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D). (NCT02728050)
Timeframe: First 28 days of treatment
| Intervention | mg BID (Number) |
|---|
| CLAGM+Sorafenib Phase 1 | 400 |
Phase I and II: Rate of Minimal Residual Disease Negative (MRDneg) Complete Response (CR)
We will determine if the addition of sorafenib to CLAG-M improves the rate of MRDneg CR compared to our institution's historical control of CLAG-M alone in adults with newly-diagnosed AML/high-risk MDS. (NCT02728050)
Timeframe: 56 days (2 cycles of induction chemotherapy)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1, Dose Level 1 | 3 |
| Phase 1, Dose Level 2 | 6 |
| Phase 1, Dose Level 3 | 8 |
| Phase 1, Dose Level 4 | 4 |
| Phase 1, Dose Level 5 | 9 |
| Phase 1, Dose Level 6 | 7 |
| Phase 2, Dose Level 6 | 31 |
Relapse-free Survival (RFS)
12-month relapse free survival (RFS) (NCT02728050)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| CLAGM+Sorafenib Phase 2 | 82 |
Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years.
Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions. (NCT00074165)
Timeframe: 2 years
| Intervention | Participants (Number) |
|---|
| Rituximab and Carboplatin | 1 |
Overall Survival (OS)
Time from randomization to death. Patients alive at last follow-up were censored. (NCT00046930)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter
| Intervention | Months (Median) |
|---|
| Zosuquidar | 7.23 |
| Placebo | 9.43 |
Progression-free Survival (PFS)
Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored. (NCT00046930)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter
| Intervention | Months (Median) |
|---|
| Zosuquidar | 3.02 |
| Placebo | 2.04 |
Response
Number of eligible participants in each response category. Categories, based on peripheral blood counts and bone marrow aspirate and biopsy, include complete remission (CR), partial remission (PR), morphologic complete remission (MCR), and relapse. (NCT00046930)
Timeframe: Assessed at the end of induction
| Intervention | Participants (Number) |
|---|
| Complete Remission | Morphologic Complete Remission | Partial Remission | Relapse | Unevaluable |
|---|
| Placebo | 96 | 12 | 0 | 90 | 23 |
,| Zosuquidar | 98 | 12 | 2 | 67 | 33 |
EFS in High Risk APL Patients
EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits. (NCT02339740)
Timeframe: Up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| High Risk | 96.1 |
Event-free Survival (EFS) in Standard Risk Acute Promyelocytic Leukemia (APL) Patients
EFS is defined as the time from on study to failure to achieve hematological complete response (CR) prior to start of consolidation, persistence of molecular positive disease after minimal residual disease (MRD) positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. The Kaplan-Meier method will be used to estimate 2-year EFS along with 90% log-minus-log transformed confidence limits. (NCT02339740)
Timeframe: Up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| Standard Risk | 97.9 |
Continuous Complete Remission (CCR) Rate
Will be testing using an exact binomial test (NCT00792948)
Timeframe: 18 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment | 57 |
Overall Survival (OS)
OS will be estimated using the method of Kaplan-Meier. (NCT00792948)
Timeframe: From the date of initial registration on the study until death from any cause, assessed up to 5 years
| Intervention | Probability of surviving 12 months (Number) |
|---|
| Treatment | 0.88 |
Relapse-free Survival (RFS) After Allogeneic Stem Cell Transplantation
Will be estimated using the method of Kaplan-Meier. (NCT00792948)
Timeframe: 12 months
| Intervention | Probability of 12-month RFS (Number) |
|---|
| Treatment | 0.83 |
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
Mean and standard deviation of area under the concentration time curve. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. (NCT00369317)
Timeframe: Days 1, 2, 8, and 9 of induction II
| Intervention | Mean micromolar x minutes (Mean) |
|---|
| Treatment (Combination Chemotherapy) | 1337.279 |
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
Mean and standard deviation of half-life of elimination. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. (NCT00369317)
Timeframe: Days 1, 2, 8, and 9 of induction II
| Intervention | Mean minutes (Mean) |
|---|
| Treatment (Combination Chemotherapy) | 306.156034 |
Cytarabine Drug Sensitivity by R-Strip (MicroMath) Curve Fitting Program
Mean and standard deviation of peak plasma concentration. Specimen draws were performed only with dose 1, day 1 of induction II of AraC. First sample drawn pre-infusion, then drawn 30 mins prior to the end of the infusion, and then drawn for 6 time periods post infusion up to 8 hours post infusion (and before the 2nd dose of AraC). Results are based from these multiple time points on Day 1 of Induction II only. (NCT00369317)
Timeframe: Days 1, 2, 8, and 9 of induction II
| Intervention | Mean micromolar (Mean) |
|---|
| Treatment (Combination Chemotherapy) | 32.69931 |
Event-free Survival (EFS) at 3 Years
(NCT00369317)
Timeframe: Time from study entry to induction failure, relapse, or death assessed at 3 years.
| Intervention | percentage (Number) |
|---|
| Treatment (Combination Chemotherapy) | 90.1 |
Induction Remission Rate
Proportion of participants with a remission after four courses of Induction therapy. (NCT00369317)
Timeframe: End of induction therapy (day 112)
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Combination Chemotherapy) | 0.984615 |
Overall Survival (OS) at 3 Years
(NCT00369317)
Timeframe: Time from study entry to death, assessed at 3 years.
| Intervention | percentage (Number) |
|---|
| Treatment (Combination Chemotherapy) | 92.7 |
Percentage of Patients Experiencing Grade 3 or 4 Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Proportion of participants with at least one grade 3 or higher adverse event during therapy. (NCT00369317)
Timeframe: From the beginning of induction therapy to the end of intensification therapy
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Combination Chemotherapy) | 0.911765 |
Prevalence of Leukemia Phenotype of DS Patients < 4 Years of Age at Diagnosis by Flow Cytometry
Proportion of participants having megakaryoblastic subtype (AMkL) phenotype among patients with phenotype data available. (NCT00369317)
Timeframe: At the start of therapy
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Combination Chemotherapy) | 0.45122 |
Prevalence of of GATA1 Mutations of DS Patients < 4 Years of Age at Diagnosis
Proportion of participants having GATA1 mutation among patients with phenotype data available. (NCT00369317)
Timeframe: At baseline and at the end of therapy (intensification) or disease relapse
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Combination Chemotherapy) | 0.891304 |
Proportions of Patients in Morphologic Remission With Positive MRD by Flow Cytometry
Proportion of participants in complete remission by morphology and with positive MRD by flow cytometry among patients having evaluable remission and MRD assessment. (NCT00369317)
Timeframe: After Induction I therapy (day 28 from start of therapy)
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Combination Chemotherapy) | 0.0935254 |
Event-free Survival of Standard Risk Patients Who Receive Chemotherapy Alone.
Kaplan-Meier estimate of the probability of being alive and free of relapse or second malignancy three years after protocol enrollment (NCT00703820)
Timeframe: 3 years after completion of therapy
| Intervention | Percentage of participants (Number) |
|---|
| Cytarabine+Daunorubicin+Etoposide | 55.6 |
| Clofarabine+Cytarabine | 54.3 |
Event-free Survival of Standard Risk Patients Who Receive Chemotherapy Followed by Natural Killer Cell Transplantation.
Kaplan-Meier estimate of the probability of being alive and free of relapse or second malignancy three years after protocol enrollment (NCT00703820)
Timeframe: 3 years after completion of therapy
| Intervention | Percentage of participants (Number) |
|---|
| Cytarabine+Daunorubicin+Etoposide | 55.6 |
| Clofarabine+Cytarabine | 77.8 |
Disease Free Survival (DFS)
Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05. (NCT01256398)
Timeframe: 10 years
| Intervention | Months (Median) |
|---|
| Treatment (Chemotherapy, Transplant) | 29.7 |
Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause
Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05. (NCT01256398)
Timeframe: At 3 years after CR
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Chemotherapy, Transplant) | 52.6 |
Feasibility of Maintenance Therapy in This Patient Population (Restricted to Those Patients Achieving a CR). Feasibility Will be Defined as the Number of Deaths Ocuring.
Proportions will be estimated based on the combined and individual cohorts. (NCT01256398)
Timeframe: 10 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, Transplant) | 5 |
Overall Survival (OS)
Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05. (NCT01256398)
Timeframe: 10 years
| Intervention | Months (Median) |
|---|
| Treatment (Chemotherapy, Transplant) | 55.9 |
Probability of Being BCR-ABL Negative in the Bone Marrow and Peripheral Blood at the Completion of the CNS Prophylaxis Course (Restricted to Those Patients Achieving a CR)
Proportions will be estimated based on the combined and individual cohorts. (NCT01256398)
Timeframe: 10 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Chemotherapy, Transplant) | 0.667 |
Response
Proportion of patients reaching a CR. A CR requires the following: an absolute neutrophil count (segs and bands) >1000/μL, no circulating blasts, platelets >100,000/μL; adequate bone marrow cellularity with trilineage hematopoiesis, and <5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement). (NCT01256398)
Timeframe: 10 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Chemotherapy, Transplant) | .9846 |
12-month PFS (Progression Free Survival) of Treatment With Ixazomib in Combination With DA-EPOCH-R (Phase II)
12-month PFS will be defined as the percentage of patients alive and progression free 12 months from start of therapy. Patients lost to follow up will be censored from last point of contact. PFS was calculated using a Kplan-meier estimation with the probability of patients being progression free at 12 months, presented as the percentage based on this probability. (NCT02481310)
Timeframe: Up to 12 months from initiation of treatment
| Intervention | probability (%) of patients alive (Number) |
|---|
| Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | 75.84 |
To Determine the Recommended Phase II Dose (RP2D) of Ixazomib in Combination With DA-EPOCH-R.
"The RP2D will be determined by the evaluation of dose-limiting toxicities (DLT) to find the Maximum Tolerated Dose (MTD) which will constitute the RP2D. DLTs will be defined as the occurrence of ≥ Grade 3 toxicity experienced during the first cycle (3 weeks or 21 days) of study treatment, will be determined, except for cytopenias.~The dose of ixazomib will start at 2.3 mg weekly (for phase I patients) when given concurrently with DA-EPOCH-R. Single-subject cohorts (escalating in ixazomib dose) will be enrolled until the MTD is encountered, after which expansion to 3-subject cohorts will be undertaken. The MTD from phase I will equate the RP2D for ixazomib given in conjunction with DA-EPOCH-R." (NCT02481310)
Timeframe: The first 21 days of treatment
| Intervention | mg (Number) |
|---|
| Treatment (Combination Chemotherapy, Rituximab, Ixazomib) | 3 |
Overall Response Rate
The Overall Response Rate was measured by the number of patients per the total treatment population who partially or completely responded to treatment. Response was evaluated according to the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. (NCT00336583)
Timeframe: up to 24 weeks
| Intervention | pariticipants (Number) |
|---|
| ESHAOx | 17 |
Worst Toxicity Grade by Patient
graded by National Cancer Institute Common Toxicity Criteria of Adverse Event version 3.0 (NCT00336583)
Timeframe: up to 24 weeks
| Intervention | participants (Number) |
|---|
| Grade 1 neutropenia | Grade 2 neutropenia | Grade 3 neutropenia | Grade 4 neutropenia | Grade 1 thrombocytopenia | Grade 2 thrombocytopenia | Grade 3 thrombocytopenia | Grade 4 thrombocytopenia |
|---|
| ESHAOx | 3 | 3 | 2 | 13 | 4 | 3 | 3 | 6 |
1 Year Progression-Free Survival
1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999). (NCT01661881)
Timeframe: Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months.
| Intervention | probability (Number) |
|---|
| RB/RC | .96 |
Autologous Stem Cell Transplant (ASCT) Rate
ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT) (NCT01661881)
Timeframe: All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction.
| Intervention | proportion of participants (Number) |
|---|
| RB/RC | .91 |
Complete Remission (CR) Rate After 6 Cycles
The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline. (NCT01661881)
Timeframe: Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days.
| Intervention | proportion of participants (Number) |
|---|
| RB/RC | .96 |
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
(NCT02587598)
Timeframe: Approximately 7 months
| Intervention | Participants (Number) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 4 |
| Parts 1 and 2: INCB053914 50 mg BID | 11 |
| Parts 1 and 2: INB053914 65 mg BID | 4 |
| Parts 1 and 2: INB053914 80 mg BID | 21 |
| Parts 1 and 2: INB053914 100 mg BID | 12 |
| Parts 1 and 2: INB053914 115 mg BID | 6 |
| Parts 3 and 4: INCB053914 50 mg BID + Cytarabine | 6 |
| Parts 3 and 4: INCB053914 50 mg BID + Azacitidine | 7 |
| Parts 3 and 4: INCB053914 80 mg BID + Azacitine | 9 |
| Parts 3 & 4: INCB 053914 50 mg BID + Ruxolitinib | 3 |
| Parts 3 & 4: INCB 053914 80 mg + Ruxolitinib | 14 |
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay (NCT02587598)
Timeframe: 1 month
| Intervention | Percentage of Inhibition (Mean) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 41 |
| Parts 1 and 2: INCB053914 50 mg BID | 37 |
| Parts 1 and 2: INB053914 65 mg BID | 68 |
| Parts 1 and 2: INB053914 80 mg BID | 78 |
| Parts 1 and 2: INB053914 100 mg BID | 55 |
| Parts 1 and 2: INB053914 115 mg BID | 58 |
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | nM*h (Mean) |
|---|
| Parts 3 & 4: INCB053914 80 mg BID + Azacitidine | 11000 |
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
(NCT02587598)
Timeframe: Cycle 1 Day 5
| Intervention | nM*h (Mean) |
|---|
| Parts 3 & 4: INCB053914 50 mg BID + Cytarabine | 2860 |
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
(NCT02587598)
Timeframe: Regimen 2 Week 4
| Intervention | nM*h (Mean) |
|---|
| Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib | 3060 |
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | nM*h (Mean) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 4140 |
| Parts 1 and 2: INCB053914 50 mg BID | 1290 |
| Parts 1 and 2: INB053914 65 mg BID | 2480 |
| Parts 1 and 2: INB053914 80 mg BID | 3940 |
| Parts 1 and 2: INB053914 100 mg BID | 5410 |
| Parts 1 and 2: INB053914 115 mg BID | 5630 |
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | L/h (Mean) |
|---|
| Parts 3 & 4: INCB053914 80 mg BID + Azacitidine | 30.8 |
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
(NCT02587598)
Timeframe: Cycle 1 Day 5
| Intervention | L/hr (Mean) |
|---|
| Parts 3 & 4: INCB053914 50 mg BID + Cytarabine | 122 |
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
(NCT02587598)
Timeframe: Regimen 2 Week 4
| Intervention | L/h (Mean) |
|---|
| Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib | 69.7 |
Pharmacokinetics: CL/F of INCB053914 Monotherapy
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | L/h (Mean) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 47.2 |
| Parts 1 and 2: INCB053914 50 mg BID | 132 |
| Parts 1 and 2: INB053914 65 mg BID | 95.1 |
| Parts 1 and 2: INB053914 80 mg BID | 71.2 |
| Parts 1 and 2: INB053914 100 mg BID | 85.2 |
| Parts 1 and 2: INB053914 115 mg BID | 39.8 |
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INCB053914 80 mg BID + Azacitidine | 1320 |
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
(NCT02587598)
Timeframe: Cycle 1 Day 5
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INCB053914 50 mg BID + Cytarabine | 423 |
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
(NCT02587598)
Timeframe: Regimen 2 Week 4
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib | 541 |
Pharmacokinetics: Cmax of INCB053914 Monotherapy
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | nM (Mean) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 352 |
| Parts 1 and 2: INCB053914 50 mg BID | 227 |
| Parts 1 and 2: INB053914 65 mg BID | 333 |
| Parts 1 and 2: INB053914 80 mg BID | 591 |
| Parts 1 and 2: INB053914 100 mg BID | 796 |
| Parts 1 and 2: INB053914 115 mg BID | 578 |
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INCB053914 80 mg BID + Azacitidine | 513 |
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
(NCT02587598)
Timeframe: Cycle 1 Day 5
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INCB053914 50 mg BID + Cytarabine | 139 |
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
(NCT02587598)
Timeframe: Regimen 2 Week 4
| Intervention | nM (Mean) |
|---|
| Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib | 104 |
Pharmacokinetics: Ctau of INCB053914 Monotherapy
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | L/h (Mean) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 98.2 |
| Parts 1 and 2: INCB053914 50 mg BID | 65.7 |
| Parts 1 and 2: INB053914 65 mg BID | 132 |
| Parts 1 and 2: INB053914 80 mg BID | 213 |
| Parts 1 and 2: INB053914 100 mg BID | 293 |
| Parts 1 and 2: INB053914 115 mg BID | 410 |
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | h (Median) |
|---|
| Parts 3 & 4: INCB053914 80 mg BID + Azacitidine | 2 |
Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
(NCT02587598)
Timeframe: Cycle 1 Day 5
| Intervention | h (Median) |
|---|
| Parts 3 & 4: INCB053914 50 mg BID + Cytarabine | 1.52 |
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
(NCT02587598)
Timeframe: Regimen 2 Week 4
| Intervention | h (Median) |
|---|
| Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib | 2.02 |
Pharmacokinetics: Tmax of INCB053914 Monotherapy
(NCT02587598)
Timeframe: Cycle 1 Day 8
| Intervention | hour (Median) |
|---|
| Parts 1 and 2: INCB053914 100 mg QD | 2.0 |
| Parts 1 and 2: INCB053914 50 mg BID | 1.0 |
| Parts 1 and 2: INB053914 65 mg BID | 2.0 |
| Parts 1 and 2: INB053914 80 mg BID | 1.5 |
| Parts 1 and 2: INB053914 100 mg BID | 1.0 |
| Parts 1 and 2: INB053914 115 mg BID | NA |
Maximum Tolerated Dose (MTD) of Bortezomib
The maximum tolerated dose (MTD) is defined to be the dose cohort below which 3 of 6 patients experience dose limiting toxicity (DLT), or the highest dose cohort of 1.5 mg/m², if 2 DLT were not observed at any dose cohort. (NCT00571493)
Timeframe: 14 months
| Intervention | mg/m² (Number) |
|---|
| Phase I | 1.5 |
| Phase II | 1.0 |
Preliminary Estimate of Overall Response Rate (ORR)
To obtain a preliminary estimate of overall response rate (ORR). The overall response rate is calculated as the number of patients who achieved complete response (CR) and partial response (PR) divided by the total number of evaluable patients. (NCT00571493)
Timeframe: 100 day post autologous hematopoietic stem cell transplantation (ASCT), one year post ASCT
| Intervention | participants (Number) |
|---|
| Overall Response Rate (100 days after transplant) | Overall Response Rate (1 year after transplant) |
|---|
| Phase II: Overall Response Rate | 38 | 33 |
Progression-free Survival (PFS), and Overall Survival (OS)
To obtain a preliminary estimate of PFS and OS. Overall survival (OS) is defined as time from the first chemotherapy administered on the transplant trial until death from any cause. Progression free survival (PFS)is defined as time from therapy until relapse, progression, or death from any cause. (NCT00571493)
Timeframe: one year post autologous hematopoietic stem cell transplantation (ASCT) , 5 years post ASCT
| Intervention | percentage of participants (Number) |
|---|
| Progression Free Survival 1 year after transplant | Overall Survival 1 year after transplant | Progression Free Survival 5 years after transplant | Overall Survival 5 years after transplant |
|---|
| Phase II: Progression Free Survival and Overall Survival | 83 | 91 | 32 | 67 |
Event Free Survival (EFS)
The Kaplan-Meier method will be used to estimate the 2-year EFS for each of the treatment regimens. (NCT01979536)
Timeframe: Time from study entry until progressive disease, relapse, or death, assessed up to 2 years
| Intervention | Percentage of patients (Number) |
|---|
| Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 78.8 |
| Arm CZ (Crizotinib, Combination Chemotherapy) | 76.8 |
Occurrence of Grade 3+ Non-hematologic Adverse Events
Will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicities will be summarized by individual toxicity counts separated by arm. (NCT01979536)
Timeframe: Up to 60 months
| Intervention | Percentage of patients (Number) |
|---|
| Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 80.6 |
| Arm CZ (Crizotinib, Combination Chemotherapy) | 87.9 |
Prognostic Significance of Minimal Residual Disease
Analyzed by estimating the 2-year EFS of negative MRD and positive MRD by arm. Minimal disease was performed using serial assessments of the t(2;5)(p23;q35) NPM-ALK fusion transcript using quantitative RT-PCR. Quantitative RT-PCR was performed by extracting total RNA from peripheral blood specimens. Peripheral blood samples were obtained at baseline, on day 1 of cycle 1, and on day 1 of cycle 2. The normalized copy numbers (NCN) were expressed as copy numbers of NPM-ALK per 104 copies of ABL. Minimal disease (MDD) was defined as >10 NCN at baseline. (NCT01979536)
Timeframe: Baseline up to progressive disease, relapse, or death, assessed up to 2 years
| Intervention | Percentage of patients (Number) |
|---|
| MRD Negative Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 89 |
| MRD Positive Arm BV (Brentuximab Vedotin, Combination Chemotherapy) | 52.6 |
| MRD Negative Arm CZ (Crizotinib, Combination Chemotherapy) | 85.6 |
| MRD Positive Arm CZ (Crizotinib, Combination Chemotherapy) | 58.1 |
Overall Survival in Patients 65 Years or Older Who Have Newly Diagnosed de Novo or Secondary AML.
The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first. (NCT00260832)
Timeframe: The interval from date of randomization to the date of death from any cause or the last date the subject was known to be alive or 5 years whichever occurs first.
| Intervention | months (Median) |
|---|
| Cytarabine or Supportive Care | 5.0 |
| Dacogen (Decitabine) Only | 7.7 |
Percentage of Participants With Complete Remission (CR) Plus Complete Remission With Incomplete Platelet Recovery (CRp)
Morphologic CR plus CRp rate where Morphologic leukemia-free state defined as less that (<) 5 percent (%) blasts in an aspirate sample with marrow spicules and a count of greater than or equal to (>=) 200 nucleated cells (there should have been no blasts with Auer rods or persistence of extramedullary disease) plus absolute neutrophil count (ANC) greater than (>)1,000 per microliter (/mcL), platelet count of >=100,000/mcL, and the participant must have been independent of transfusions for at least 1 week before each assessment. There was no duration requirement for confirmation of this designation and Morphologic CR without the requirement of platelet count >=100,000/mcL. (NCT00260832)
Timeframe: Post randomization when at least one post-baseline bone marrow assessment or peripheral blood count data available (up to 29.5 months)
| Intervention | percentage of participants (Number) |
|---|
| Cytarabine or Supportive Care | 7.8 |
| Dacogen (Decitabine) Only | 17.8 |
Event-Free Survival (EFS)
Event -Free Survival (EFS) EFS was calculated with Kaplan-Meier estimates. Event-free survival (EFS), defined as the time to no response to intensive induction therapy, relapse, or death of any cause, whichever comes first. (NCT00422591)
Timeframe: from treatment initiation until treatment failure, relapse, or death
| Intervention | Months (Median) |
|---|
| Idarubicin + Cytarabine | 4.7 |
Overall Survival (OS)
Overall Survival (OS) was calculated with Kaplan-Meier estimates. OS was calculated from the time of treatment initiation until death. (NCT00422591)
Timeframe: Until death or loss of follow-up
| Intervention | Months (Median) |
|---|
| Idarubicin + Cytarabine | 11.3 |
5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups
Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method. (NCT00039377)
Timeframe: 5 years from CR
| Intervention | percentage of patients (Number) |
|---|
| Patients With HLA-matched Sibling Donor | 46 |
| Patients Without HLA-matched Sibling Donors | 47 |
5 Year Overall Survival for Autologous & Allogeneic Transplant Groups
Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method. (NCT00039377)
Timeframe: 5 years from registration
| Intervention | percentage of patients (Number) |
|---|
| Patients With HLA-matched Sibling Donor | 53 |
| Patients Without HLA-matched Sibling Donors | 51 |
Disease Free Survival
"Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method.~A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month." (NCT00039377)
Timeframe: Duration of treatment (up to 10 years)
| Intervention | years (Median) |
|---|
| Entire Cohort | 1.7 |
Overall Survival
Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method. (NCT00039377)
Timeframe: Duration of study (up to 10 years)
| Intervention | years (Median) |
|---|
| Entire Cohort | 3.6 |
Number of Participants Who Achieved a BCR-ABL Response at 12 Months
"BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR).~Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene~MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally)." (NCT00039377)
Timeframe: 12 months
| Intervention | participants (Number) |
|---|
| Complete Molecular Response | Major Molecular Response |
|---|
| Entire Cohort | 9 | 4 |
Objective Response
Determine the overall objective response. CR rate [as measured from the start of ICE, (or high dose CTX) to the end of transplant for those who receive it, or the end of ICE for those who do not].Complete response (CR): No evidence of Hodgkin's disease determined clinically, radiologically or pathologically when indicated (NCT00003631)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Failure | Minor Response (MR) | Partial Response (PR) | Progression Free (P-Free) | Complete Response (CR) | Progression of Disease (POD) |
|---|
| Group A - Favorable Prognostic Group | 3 | 2 | 1 | 41 | 0 | 0 |
,| Group B - Intermediate Prognostic Group | 6 | 1 | 2 | 31 | 2 | 1 |
,| Group C - Unfavorable Prognostic Group | 3 | 0 | 4 | 7 | 1 | 0 |
EFS for Standard (SR) and Intermediate Risk (IR) T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no Cranial Radiation Therapy [CRT]) and Similar Patients on AALL0434 (Received CRT)
EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| AALL1231 T-ALL Patients | 88.3 |
| AALL0434 T-ALL Patients | 88.8 |
EFS for Very High Risk (VHR) T-ALL Patients Treated With High Risk (HR) Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Become Minimal Residual Disease (MRD) Negative and Those Who Remain MRD Positive at the End of HR Block 3
EFS will be calculated as time from the end of the three high-risk blocks of therapy to first event (relapse, second malignancy, remission death) or date of last contact. (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| VHR T-ALL MRD Undetectable | 25.0 |
| VHR T-ALL MRD Detectable | 88.9 |
EFS for Very High Risk (VHR) T-LLy Patients Treated With HR Berlin-Frankfurt-Munster (BFM) Intensification Blocks Who Have Complete or Partial Remission and Those Who do Not Respond
EFS for very high risk (VHR) T-LLy patients treated with HR Berlin-Frankfurt-Munster (BFM) intensification blocks who have complete or partial remission and those who do not respond (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| VHR T-LLy (CR/PR) | 0 |
Event-free Survival (EFS) for Modified Augmented Berlin-Frankfurt-Munster Backbone With or Without Bortezomib in All Randomized Patients
EFS is calculated as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignancy, remission death) or date of last contact. Three-year EFS rates will be calculated for both groups. (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Arm A (Combination Chemotherapy) | 81.7 |
| Arm B (Combination Chemotherapy, Bortezomib) | 85.1 |
Toxicity Rates Associated With Modified Standard Therapy, Including Dexamethasone and Additional Pegaspargase
Percentage of patients who experienced Grade 3 or higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (NCT02112916)
Timeframe: 3 years from start of therapy by patient
| Intervention | Percentage of participants (Number) |
|---|
| Total Patients | 78.0 |
Cumulative Incidence Rates of Isolated Central Nervous System (CNS) Relapse for SR and IR T-ALL Patients on the Non-bortezomib Containing Arm on This Study (no CRT) and Similar Patients on AALL0434 (Receive CRT)
Cumulative incidence of isolated CNS relapse adjusting for competing risks using the method of: Gray R, A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1141:1154, 1988 (NCT02112916)
Timeframe: 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Isolated CNS Relapse | Isolated Bone Marrow Relapse | Combined Bone Marrow Relapse |
|---|
| AALL0434 T-ALL Patients | 2.2 | 3.0 | 1.8 |
,| AALL1231 T-ALL Patients | 3.6 | 1.4 | 1.3 |
Disease Free Survival (DFS) of High-risk (HR) and Intermediate-risk (IR) Relapse Patients
DFS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). DFS is calculated as the time from randomization to date of first event (treatment failure, relapse, second malignancy, remission death) or date of last contact. Two-year DFS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated. (NCT02101853)
Timeframe: Up to 2 years from date of randomization
| Intervention | percentage of participants (Number) |
|---|
| Arm A (HR and IR Control) | 39.04 |
| Arm B (HR and IR Blinatumomab) | 54.44 |
Disease Free Survival (DFS) of Low Risk (LR) Relapse Patients
DFS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). DFS is calculated as the time from randomization to date of first event (relapse, second malignancy, remission death) or date of last contact. Three-year DFS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated. (NCT02101853)
Timeframe: Up to 3 years from date of randomization
| Intervention | percentage of participants (Number) |
|---|
| Arm C (LR Control) | 58.94 |
| Arm D (LR Blinatumomab) | 67.00 |
Overall Survival (OS) of HR and IR Relapse Patients
OS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Two-year OS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated. (NCT02101853)
Timeframe: Up to 2 years from date of randomization
| Intervention | percentage of participants (Number) |
|---|
| Arm A (HR and IR Control) | 58.40 |
| Arm B (HR and IR Blinatumomab) | 71.33 |
Overall Survival (OS) of LR Relapse Patients
OS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Three-year OS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated. (NCT02101853)
Timeframe: Up to 3 years from date of randomization
| Intervention | percentage of participants (Number) |
|---|
| Arm C (LR Control) | 88.29 |
| Arm D (LR Blinatumomab) | 90.37 |
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I + Arm II vs. Arm III + Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| ARM I and ARM II (Combination Chemotherapy) | 91.45 |
| ARM III and ARM IV (Combination Chemotherapy) | 85.78 |
Disease-free Survival (DFS) for Randomized Methotrexate T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
Disease-free survival defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, remission death) or date of last contact for those who are event-free. (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| ARM I (Combination Chemotherapy) | 91.76 |
| ARM II (Combination Chemotherapy) | 90.53 |
| ARM III (Combination Chemotherapy) | 86.06 |
| ARM IV (Combination Chemotherapy) | 84.89 |
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I + Arm III vs. Arm II + Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| ARM I and ARM III (Combination Chemotherapy) | 82.96 |
| ARM II and ARM IV (Combination Chemotherapy) | 88.30 |
Disease-free Survival (DFS) for Randomized Nelarabine T-ALL Cohort (Arm I vs. Arm II vs. Arm III vs. Arm IV)
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| ARM I (Combination Chemotherapy) | 89.01 |
| ARM II (Combination Chemotherapy) | 90.53 |
| ARM III (Combination Chemotherapy) | 78.07 |
| ARM IV (Combination Chemotherapy) | 86.46 |
Cumulative Incidence of CNS Relapse for T-ALL by Risk Group
Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation. (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| Intermediate Risk | High Risk |
|---|
| ARM II (Combination Chemotherapy) | 1.08 | 0 |
,| ARM IV (Combination Chemotherapy) | 0.85 | 3.45 |
Cumulative Incidence of CNS Relapse for T-ALL by Risk Group
Cumulative incidence of CNS relapse adjusting for DFS events, was calculated using the method Gray et. al. High risk patients receive cranial radiation and low risk patients receive no cranial radiation. (NCT00408005)
Timeframe: 4 years from randomization at the end of induction
| Intervention | percent probability (Number) |
|---|
| Low Risk | Intermediate Risk | High Risk |
|---|
| ARM I (Combination Chemotherapy) | 1.85 | 1.16 | 3.64 |
,| ARM III (Combination Chemotherapy) | 1.92 | 9.1 | 6.52 |
Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00408005)
Timeframe: 4 years from end of induction
| Intervention | percent probability (Number) |
|---|
| High Risk | Induction Failure |
|---|
| ARM II (Combination Chemotherapy) | 85.0 | 100 |
Disease-free Survival (DFS) for T-cell Lymphoblastic Lymphoma (T-LLy) Cohort
Disease Free Probability where DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00408005)
Timeframe: 4 years from end of induction
| Intervention | percent probability (Number) |
|---|
| Standard Risk | High Risk |
|---|
| ARM I (Combination Chemotherapy) | 87.4 | 85.1 |
Comparison of the Increase in Cure Rate of High Risk ALL Without Causing More Serious Side Effects Between Interventions
Event Free Probability. (NCT00075725)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 83.2 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 81.6 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 69.1 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 91.2 |
| Prednisone, Capizzi Methotrexate <10 Years | 82.1 |
| Prednisone, Capezzi Methotrexate >= 10 Years | 73.5 |
| Predisone and High Dose Methotrexate < 10 Yrs Old | 80.8 |
| Prenisone and High Dose Methotrexate >=10 Years | 75.8 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 77.0 |
| Prenisone, Capezzi Methotrexate (Down's Syndrome) | 61.8 |
| Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | 44.4 |
Correlation of Early Marrow Response Status With MRD Negative.
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. (NCT00075725)
Timeframe: Day 29
| Intervention | participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 182 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 72 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 198 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 188 |
| Prednisone, Capizzi Methotrexate <10 Years | 195 |
| Prednisone, Capezzi Methotrexate >= 10 Years | 471 |
| Prednisone and High Dose Methotrexate < 10 Yrs Old | 190 |
| Prednisone and High Dose Methotrexate >=10 Years | 479 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 208 |
| Prednisone, Capezzi Methotrexate (Down's Syndrome) | 25 |
| Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | 3 |
| Prednisone and High Dose Methotrexate (Non Randomly Assigned) | 18 |
Correlation of Early Marrow Response Status With MRD Positive.
Bone marrow status is defined as: M1: < 5% lymphoblasts; M2: 5-25% lymphoblasts; M3: > 25% lymphoblasts. Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. (NCT00075725)
Timeframe: Day 29
| Intervention | participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 26 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 12 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 43 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 14 |
| Prednisone, Capizzi Methotrexate <10 Years | 16 |
| Prednisone, Capezzi Methotrexate >= 10 Years | 95 |
| Prednisone and High Dose Methotrexate < 10 Yrs Old | 17 |
| Prednisone and High Dose Methotrexate >=10 Years | 98 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 39 |
| Prednisone, Capezzi Methotrexate (Down's Syndrome) | 3 |
| Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | 3 |
| Prednisone and High Dose Methotrexate (Non Randomly Assigned) | 3 |
Correlation of Minimal Residual Disease (MRD) Negative With Event Free Survival (EFS).
Bone marrow MRD status is defined as negative with < 0.1 detectable leukemia cells. (NCT00075725)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 86.4 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 93.6 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 80.5 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 93.1 |
| Prednisone, Capizzi Methotrexate <10 Years | 86.5 |
| Prednisone, Capezzi Methotrexate >= 10 Years | 83.4 |
| Prednisone and High Dose Methotrexate < 10 Yrs Old | 84.2 |
| Prednisone and High Dose Methotrexate >=10 Years | 83.9 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 85.3 |
| Prednisone, Capezzi Methotrexate (Down's Syndrome) | 74.4 |
| Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | 25 |
Correlation of Minimal Residual Disease (MRD) Negative With Overall Survival (OS).
Bone marrow MRD status is defined as negative with < .01 detectable leukemia cells. (NCT00075725)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 95.4 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 92.9 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 87.4 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 98.1 |
| Prednisone, Capizzi Methotrexate <10 Years | 93.3 |
| Prednisone, Capizzi Methotrexate >= 10 Years | 90.2 |
| Prednisone and High Dose Methotrexate < 10 Yrs Old | 94.5 |
| Prednisone and High Dose Methotrexate >=10 Years | 90.5 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 91.6 |
| Prednisone, Capizzi Methotrexate (Down's Syndrome) | 78.3 |
| Dexamethasone, Capizzi Methotrexate Down Syndrome (Non Random) | 25.0 |
Correlation of Minimal Residual Disease (MRD) Positive With Event Free Survival (EFS)
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells. (NCT00075725)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 66.5 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 43.3 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 35.4 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 80 |
| Prednisone, Capizzi Methotrexate <10 Years | 34.7 |
| Prednisone, Capizzi Methotrexate >= 10 Years | 39 |
| Prednisone and High Dose Methotrexate < 10 Yrs Old | 55 |
| Prednisone and High Dose Methotrexate >=10 Years | 47.8 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 49.4 |
Correlation of Minimal Residual Disease (MRD) Positive With Overall Survival (OS)
Bone marrow MRD status is defined as positive with >= 0.1 detectable leukemia cells, and negative with < 0.1 detectable leukemia cells. (NCT00075725)
Timeframe: 5 Years
| Intervention | percentage of participants (Number) |
|---|
| Dexamethasone and Capizzi Methotrexate Patients < 10 Years | 79.2 |
| Dexamethasone, High Dose Methotrexate (Non Randomly Assigned) | 69.9 |
| Dexamethasone & Capizzi Methotrexate Patients => 10 Years Old | 65.6 |
| Dexamethasone, High Dose Methotrexate (IM) < 10 Years | 86.2 |
| Prednisone, Capizzi Methotrexate <10 Years | 93.8 |
| Prednisone, Capizzi Methotrexate >= 10 Years | 63.1 |
| Predisone and High Dose Methotrexate < 10 Yrs Old | 84.2 |
| Prednisone and High Dose Methotrexate >=10 Years | 73.6 |
| Dexamethasone, High Dose Methotrexate (IM) >= 10 Years | 74.6 |
Disease Response Assessed by Modified RECIST Criteria
Number of participants with complete response and very good partial response at the end of protocol therapy. (NCT00025259)
Timeframe: Protocol therapy: the overall duration of which is: (n=1527) an average of 137.1 days, median 133.0 days, interquartile range: 101.0, 164.0 days.
| Intervention | Number of participants (Number) |
|---|
| Arm I (Patients Off-therapy Before Callback-Induction Only) | 5 |
| Arm II (RER With CR [ABVE-PC, IFRT]) | 370 |
| Arm III (RER With CR [ABVE-PC]) | 380 |
| Arm IV (RER With Less Than CR [ABVE-PC, IFRT]) | 538 |
| Arm V (RER With PD) | 29 |
| Arm VI (SER [DECA, ABVE-PC, IFRT]) | 105 |
| Arm VII (SER [ABVE-PC, IFRT]) | 100 |
Event-free Survival
Probability of event-Free survival which is defined as the time from study entry to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact. (NCT00025259)
Timeframe: 5 years
| Intervention | Probability of survival (Number) |
|---|
| Arm I (Patients Off-therapy Before Callback-Induction Only) | 0.89 |
| Arm II (RER With CR [ABVE-PC, IFRT]) | 0.87 |
| Arm III (RER With CR [ABVE-PC]) | 0.84 |
| Arm IV (RER With Less Than CR [ABVE-PC, IFRT]) | 0.87 |
| Arm V (RER With PD) | 0.70 |
| Arm VI (SER [DECA, ABVE-PC, IFRT]) | 0.79 |
| Arm VII (SER [ABVE-PC, IFRT]) | 0.74 |
Grade 3 or 4 Non-hematologic Toxicity
Occurrence of any grade 4 non-hematologic toxicity or grade 3 non-hematologic toxicity which doesn't respond to treatment within 7 days despite recommended therapy modification, or toxic death, which is any death primarily attributable to treatment. Grade 3 is defined to be severe or medically significant but not immediate life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 refers to toxicities with life-threatening consequences; urgent intervention indicated. (NCT00025259)
Timeframe: Protocol therapy: the overall duration of which is: (n=1684) an average of 137.3 days, median 133.0 days, interquartile range: 101.0, 164.0 days.
| Intervention | Number of participants (Number) |
|---|
| Arm I (Patients Off-therapy Before Callback-Induction Only) | 10 |
| Arm II (RER With CR [ABVE-PC, IFRT]) | 153 |
| Arm III (RER With CR [ABVE-PC]) | 130 |
| Arm IV (RER With Less Than CR [ABVE-PC, IFRT]) | 216 |
| Arm V (RER With PD) | 11 |
| Arm VI (SER [DECA, ABVE-PC, IFRT]) | 62 |
| Arm VII (SER [ABVE-PC, IFRT]) | 45 |
Overall Survival
Probability of overall survival which is defined as the time from study entry to death from any cause. Patients alive where censored at last contact. (NCT00025259)
Timeframe: 5 years
| Intervention | Probability of survival (Number) |
|---|
| Arm I (Patients Off-therapy Before Callback-Induction Only) | 0.93 |
| Arm II (RER With CR [ABVE-PC, IFRT]) | 0.98 |
| Arm III (RER With CR [ABVE-PC]) | 0.98 |
| Arm IV (RER With Less Than CR [ABVE-PC, IFRT]) | 0.98 |
| Arm VI (SER [DECA, ABVE-PC, IFRT]) | 0.96 |
| Arm VII (SER [ABVE-PC, IFRT]) | 0.93 |
Complete Response Rate
To evaluate the complete (CR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy (NCT00732498)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| ESHAP Followed by Zevalin and Rituximab | 10 |
Median Time to Progression
To evaluate the median TTP of patients with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy. (NCT00732498)
Timeframe: 5 years
| Intervention | months (Median) |
|---|
| ESHAP Followed by Zevalin and Rituximab | 10 |
Overall Response Rate
To evaluate the overall (ORR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy. Descriptive and summary statistics for demographic and clinical variables obtained. The incidences of reported adverse events (AEs) tabulated. Kaplan-Meier survival analysis for PFS and OS performed on TPP. All the analyses were performed using Stata [12]. (NCT00732498)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| ESHAP Followed by Zevalin and Rituximab | 77.3 |
Progression-free Survival at 1 Year
To evaluate the 1-year progression-free survival (PFS) of patients with relapsed follicular non-Hodgkin's lymphoma (NHL) treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy. (NCT00732498)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| ESHAP Followed by Zevalin and Rituximab | 38 |
Complete Response or Complete Response With Incomplete Count Recovery
Complete response or complete response with incomplete count recovery, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study (NCT03071276)
Timeframe: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
| Intervention | percentage of participants (Number) |
|---|
| Interventions: Selinexor, Fludarabine, and Cytarabine | 50.0 |
Complete Response
Complete response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study (NCT03071276)
Timeframe: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
| Intervention | percentage of participants (Number) |
|---|
| Interventions: Selinexor, Fludarabine, and Cytarabine | 46.4 |
The Overall Response (OR) Rate (Complete Response + Incomplete Count Recovery + Partial Response)
Complete response or complete response with incomplete count recovery or partial response, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study (NCT03071276)
Timeframe: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days)
| Intervention | percentage of participants (Number) |
|---|
| Interventions: Selinexor, Fludarabine, and Cytarabine | 53.6 |
Duration of Objective Response Rate (ORR) [Part 1]
"Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause.~MLFS: BM blasts <5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC>1000/ul and platelet >100,000/ul; independence from red cell transfusions.~CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM.~CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.~PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.~Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD." (NCT02954653)
Timeframe: 16 weeks
| Intervention | months (Median) |
|---|
| Part 1: PF-06747143 0.3 mg/kg | NA |
| Part 1: PF-06747143 1 mg/kg | NA |
Number of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]
DLTs were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and were defined as any of a predefined set of unacceptable hematologic and non-hematologic adverse events (AEs) occurring in the first treatment cycle unless clearly determined unrelated to PF-06747143. In addition, clinically important or persistent toxicities that were not included in the pre-specified criteria could be considered a DLT following review by the investigators and sponsor. (NCT02954653)
Timeframe: Day 1 to Day 28 of Cycle 1
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: PF-06747143 0.3 mg/kg | 0 |
| Part 1: PF-06747143 1 mg/kg | 1 |
Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 1]
"Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi).~MLFS: Bone marrow (BM) blasts <5%; absence of blasts with Auer rods and extramedullary disease (EMD).~CR: MLFS criteria; absolute neutrophil count (ANC)>1000/ul and platelet >100,000/ul; independence from red cell transfusions.~CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM.~CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.~PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels (NCT02954653)
Timeframe: 16 weeks
| Intervention | percentage of participants (Number) |
|---|
| Part 1: PF-06747143 0.3 mg/kg | NA |
| Part 1: PF-06747143 1 mg/kg | NA |
Progression Free Survival [Part 1]
Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD). (NCT02954653)
Timeframe: 16 weeks
| Intervention | months (Median) |
|---|
| Part 1: PF-06747143 0.3 mg/kg | NA |
| Part 1: PF-06747143 1 mg/kg | NA |
Incidence of Anti-Drug Antibodies (ADA) Against PF-06747143 [Part 1]
Samples were tested for ADA using a validated assay. Number of participants with positive ADA samples was determined. (NCT02954653)
Timeframe: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 15 | Cycle 2 Day 1 | End of treatment |
|---|
| Part 1: PF-06747143 0.3 mg/kg | 0 | 0 | 0 | 0 |
,| Part 1: PF-06747143 1 mg/kg | 1 | 0 | 0 | 0 |
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs. (NCT02954653)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Part 1: PF-06747143 0.3 mg/kg | 0 | 1 | 0 | 1 | 1 |
,| Part 1: PF-06747143 1 mg/kg | 0 | 0 | 0 | 3 | 1 |
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Part 1]
An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs included non-serious AEs and SAEs. Causality to study treatment was determined by the investigator. (NCT02954653)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| AE (all causality) | AE (treatment related) | SAE (all causality) | SAE (treatment related) |
|---|
| Part 1: PF-06747143 0.3 mg/kg | 3 | 3 | 1 | 0 |
,| Part 1: PF-06747143 1 mg/kg | 4 | 3 | 3 | 1 |
Number of Participants With Chemistry Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
Chemistry laboratory abnormalities included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Each laboratory parameter was graded per NCI CTCAE version 4.03. (NCT02954653)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| ALT72525522 | ALT72525523 | Alkaline phosphatase72525522 | Alkaline phosphatase72525523 | AST72525522 | AST72525523 | Bilirubin (total)72525522 | Bilirubin (total)72525523 | Creatinine72525522 | Creatinine72525523 | Hypercalcemia72525522 | Hypercalcemia72525523 | Hyperglycemia72525522 | Hyperglycemia72525523 | Hyperkalemia72525522 | Hyperkalemia72525523 | Hypermagnesemia72525522 | Hypermagnesemia72525523 | Hypernatremia72525522 | Hypernatremia72525523 | Hypoalbuminemia72525522 | Hypoalbuminemia72525523 | Hypocalcemia72525522 | Hypocalcemia72525523 | Hypoglycemia72525522 | Hypoglycemia72525523 | Hypokalemia72525522 | Hypokalemia72525523 | Hypomagnesemia72525522 | Hypomagnesemia72525523 | Hyponatremia72525522 | Hyponatremia72525523 | Hypophosphatemia72525522 | Hypophosphatemia72525523 |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Part 1: PF-06747143 1 mg/kg | 4 |
| Part 1: PF-06747143 0.3 mg/kg | 0 |
| Part 1: PF-06747143 0.3 mg/kg | 3 |
| Part 1: PF-06747143 1 mg/kg | 1 |
| Part 1: PF-06747143 1 mg/kg | 3 |
| Part 1: PF-06747143 0.3 mg/kg | 2 |
| Part 1: PF-06747143 0.3 mg/kg | 1 |
| Part 1: PF-06747143 1 mg/kg | 2 |
| Part 1: PF-06747143 1 mg/kg | 0 |
Number of Participants With Hematology Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
Hematology laboratory abnormalities included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophil count decreased, platelet count decreased, and white blood cell (WBC) decreased. Each laboratory parameter was graded per NCI CTCAE version 4.03. (NCT02954653)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Anemia72525522 | Anemia72525523 | Hemoglobin increased72525523 | Hemoglobin increased72525522 | Lymphocyte count increased72525523 | Lymphocyte count increased72525522 | Lymphopenia72525523 | Lymphopenia72525522 | Neutrophil count decreased72525523 | Neutrophil count decreased72525522 | Platelet count decreased72525523 | Platelet count decreased72525522 | WBC decreased72525523 | WBC decreased72525522 |
|---|
| Grade 2 | Grade 4 | Grade 0 | Grade 1 | Grade 3 |
|---|
| Part 1: PF-06747143 1 mg/kg | 3 |
| Part 1: PF-06747143 1 mg/kg | 0 |
| Part 1: PF-06747143 0.3 mg/kg | 3 |
| Part 1: PF-06747143 0.3 mg/kg | 0 |
| Part 1: PF-06747143 1 mg/kg | 1 |
| Part 1: PF-06747143 1 mg/kg | 2 |
| Part 1: PF-06747143 1 mg/kg | 4 |
| Part 1: PF-06747143 0.3 mg/kg | 1 |
Apparent Volume of Distribution of Volasertib at Steady State (VSS)
Apparent Volume of Distribution of volasertib at steady state (VSS) following Intravenous (i.v.) administration. (NCT00804856)
Timeframe: Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
| Intervention | Liter (L) (Geometric Mean) |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 10600 |
| Phase I Schedule A. Volasertib 200 mg+LDAC | 8640 |
| Phase I Schedule A. Volasertib 250 mg+LDAC | 7000 |
| Phase I Schedule A. Volasertib 300 mg+LDAC | 6320 |
| Phase I Schedule A. Volasertib 350 mg+LDAC | 5270 |
| Phase I Schedule A. Volasertib 400 mg+LDAC | 4830 |
| Phase I Schedule B. Volasertib 150 mg | 10300 |
| Phase I Schedule B. Volasertib 200 mg | NA |
| Phase I Schedule B. Volasertib 350 mg | 5800 |
| Phase I Schedule B. Volasertib 400 mg | 7150 |
| Phase I Schedule B. Volasertib 450 mg | 5740 |
| Phase I Schedule B. Volasertib 500 mg | 6360 |
| Phase I Schedule B. Volasertib 550 mg | 5680 |
| Phase II Schedule A. Volasertib 350 mg+LDAC. | 6130 |
Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated up to 4 Hours
"AUC0-4,norm: Area under the concentration-time curve of Cytarabine in plasma over the time interval from zero extrapolated to 4 hours. The dose normalisation was done by dividing by dose applied. Unit: nanogram*hour/milliliter/milligram: ((ng*h/mL)/mg).~Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol." (NCT00804856)
Timeframe: Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h after first drug administration.
| Intervention | (ng*h/mL)/mg (Geometric Mean) |
|---|
| Dose Normalized Volasertib+LDAC(Phase I,Schedule A). 150 to 400 mg Volasertib. | 3.84 |
| Dose Normalized Volasertib+LDAC (Schedule A). Phase II. 350 mg Volasertib. | 4.00 |
| Dose Normalized LDAC (Schedule C). Phase II. LDAC Monotherapy. | 3.94 |
Dose Normalized Maximum Measured Concentration of Cytarabine in Plasma (Cmax, Norm)
Cmax, norm: Maximum measured concentration of Cytarabine in plasma. The dose normalisation was done by dividing by the dose applied. Unit: nanogram/milliliter/milligram: ((ng/mL)/mg). Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol. (NCT00804856)
Timeframe: Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
| Intervention | (ng/mL)/mg (Geometric Mean) |
|---|
| Dose Normalized Volasertib+LDAC(Phase I,Schedule A). 150 to 400 mg Volasertib. | 2.92 |
| Dose Normalized Volasertib+LDAC (Schedule A). Phase II. 350 mg Volasertib. | 2.83 |
| Dose Normalized LDAC (Schedule C). Phase II. LDAC Monotherapy. | 2.36 |
Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination With LDAC (Schedule A) and Volasertib Monotherapy (Schedule B)
"To determine the Maximum tolerated dose (MTD), dose escalation was conducted following the 3+3 design with de-escalation. The MTD was defined as the highest dose at which 6 patients had been treated and less than 2 patients experienced a Dose limiting toxicity (DLT) within the first cycle of treatment. The MTD was defined based on safety data from the first cycle only.~DLT is defined as drug related Common terminology criteria for adverse events (CTCAE) grade ≥ 3 nonhaematological toxicity (excluding: untreated nausea, untreated vomiting, CTCAE grade 3 untreated diarrhoea, CTCAE grade 3 febrile neutropenia and CTCAE grade 3 infection with grade 3 or 4 neutrophils).~In patients with complete remission with incomplete blood count recovery (CRi) or partial remission (PR), persistent CTCAE grade 4 neutropenia or thrombocytopenia until three weeks after the end of the treatment cycle will be regarded a DLT." (NCT00804856)
Timeframe: First Treatment cycle, up to 28 days.
| Intervention | milligram (mg) (Number) |
|---|
| Phase I Schedule A. Volasertib+LDAC | 350 |
| Phase I Schedule B. Volasertib | 450 |
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
A DLT was defined as a drug related CTCAE (Common Toxicity Criteria for Adverse Events) Grade ≥3 non-haematological toxicity (excluding untreated nausea, untreated vomiting, Grade 3 untreated diarrhea, Grade 3 febrile neutropenia, and Grade 3 infection with Grade 3 or 4 neutrophils). In patients with CRi (Complete Remission with Incomplete Blood Count Recovery) or PR (Partial Remission), persistent Grade 4 neutropenia or thrombocytopenia for 3 weeks after the end of the treatment cycle was regarded as a DLT unless the respective Grade 4 cytopenia was preexistent. In patients who required platelet substitution to maintain a Grade <4 before treatment, a Grade 4 thrombocytopenia after treatment did not constitute a DLT. (NCT00804856)
Timeframe: First Treatment cycle, up to 28 days.
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 0 |
| Phase I Schedule A. Volasertib 200 mg+LDAC | 0 |
| Phase I Schedule A. Volasertib 250 mg+LDAC | 0 |
| Phase I Schedule A. Volasertib 300 mg+LDAC | 1 |
| Phase I Schedule A. Volasertib 350 mg+LDAC | 1 |
| Phase I Schedule A. Volasertib 400 mg+LDAC | 2 |
| Total Phase I Combined. Schedule A. | 4 |
| Phase I Schedule B. Volasertib 150 mg | 1 |
| Phase I Schedule B. Volasertib 200 mg | 0 |
| Phase I Schedule B. Volasertib 350 mg | 0 |
| Phase I Schedule B. Volasertib 400 mg | 1 |
| Phase I Schedule B. Volasertib 450 mg | 1 |
| Phase I Schedule B. Volasertib 500 mg | 2 |
| Phase I Schedule B. Volasertib 550 mg | 2 |
| Total Phase I Combined. Schedule B. | 7 |
Phase I: Number of Patients With Objective Response: Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR+CRi)
"Phase I: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)).~Complete remission (CR): morphologically leukaemia-free state (i.e. bone marrow with <5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥1,000/microliter (μL) and platelets >100,000/μL.~Complete remission with incomplete blood count recovery (incomplete CR, CRi): all of the above criteria for CR were met except that neutrophils <1,000/μL or platelets <100,000/μL in the blood were not achieved." (NCT00804856)
Timeframe: The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 594 days.
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 0 |
| Phase I Schedule A. Volasertib 200 mg+LDAC | 2 |
| Phase I Schedule A. Volasertib 250 mg+LDAC | 2 |
| Phase I Schedule A. Volasertib 300 mg+LDAC | 1 |
| Phase I Schedule A. Volasertib 350 mg+LDAC | 1 |
| Phase I Schedule A. Volasertib 400 mg+LDAC | 0 |
| Total Phase I Combined. Schedule A. | 6 |
| Phase I Schedule B. Volasertib 150 mg | 0 |
| Phase I Schedule B. Volasertib 200 mg | 0 |
| Phase I Schedule B. Volasertib 350 mg | 1 |
| Phase I Schedule B. Volasertib 400 mg | 2 |
| Phase I Schedule B. Volasertib 450 mg | 2 |
| Phase I Schedule B. Volasertib 500 mg | 0 |
| Phase I Schedule B. Volasertib 550 mg | 0 |
| Total Phase I Combined. Schedule B. | 5 |
Phase II: Event Free Survival
"Event-free survival (EFS) [days] was the shortest duration of the following: (a) Date of assessment indicating PD on the response page of the eCRF (Electronic Case Report Form) - date of randomisation + 1 day (b) Date of assessment indicating clinical progressive disease (PD) on the disease or responses pages of the of eCRF- date of randomisation + 1 day (c) Date of assessment indicating PD on the patient status page of the eCRF - date of randomisation +1 day (for patients who had not been censored before this time point) (d) Death date - date of randomisation +1 day Patients not being assessed PD, clinical PD, or death during the trial were censored.~EFS was analysed with the Kaplan-Meier method for each of the treatment arms." (NCT00804856)
Timeframe: The patients that entered the trial, and measured from the date of randomization to the date of disease progression (treatment failure), relapse or death from any cause, whichever occurred first, up to 1000 days..
| Intervention | Days (Median) |
|---|
| Phase II Schedule C. LDAC | 69.0 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 169.0 |
Phase II: Number of Patients With Objective Response (Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi))
"Phase II: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)).~Complete remission (CR): morphologically leukaemia-free state (i.e. bone marrow with <5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥1,000/microliter (μL) and platelets >100,000/μL.~Complete remission with incomplete blood count recovery (incomplete CR, CRi): all of the above criteria for CR were met except that neutrophils <1,000/μL or platelets <100,000/μL in the blood were not achieved." (NCT00804856)
Timeframe: The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Schedule C. LDAC | 6 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 13 |
Phase II: Overall Survival
"Overall survival [days] = (date of death - date of randomisation + 1 day), for patients with known date of death. Overall survival (censored) [days] = (date of last trial visit or follow-up - date of randomisation + 1 day), for patients who were still alive at time of database lock.~Overall survival (OS) was analysed with the Kaplan-Meier method for each of the treatment arms." (NCT00804856)
Timeframe: The patients that entered the trial, and measured from the date of randomisation until death from any cause, up to 1100 days..
| Intervention | Days (Median) |
|---|
| Phase II Schedule C. LDAC | 158.0 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 245.0 |
Phase II: Relapse - Free Survival
"Relapse-free survival [days] = (date of first recurrence of disease or death after entering the trial - date of first occurrence of CR or CRi after entering the trial+ 1 day) for patients with a recurrence (this value should be positive).~Relapse-free survival (censored) [days] = (date of last trial visit or follow-up - date of first occurrence of CR or CRi after entering the trial + 1 day) for patients who did not experience recurrence of disease or death at the time of analysis." (NCT00804856)
Timeframe: The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence or death from any cause, whichever occurred first, up to 900 days.
| Intervention | Days (Median) |
|---|
| Phase II Schedule C. LDAC | 304.0 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 563.0 |
Phase II: Remission Duration
Remission duration analysis was defined only for patients who achieved Complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of cause. (NCT00804856)
Timeframe: The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 900 days.
| Intervention | Days (Median) |
|---|
| Phase II Schedule C. LDAC | 367.0 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 687.0 |
Phase II: Time to Remission
Time to remission [days] = (date of first occurrence of CR or CRi after entering the trial-date of randomisation + 1 day) for patients with an objective response. (NCT00804856)
Timeframe: The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 158 days.
| Intervention | Days (Median) |
|---|
| Phase II Schedule C. LDAC | 63.5 |
| Phase II Schedule A. Volasertib 350 mg+LDAC | 71.0 |
Total Clearance (CL) of Volasertib in Plasma After i.v (Intravenous) Administration of Volasertib
Total Clearance (CL) of Volasertib in Plasma after Intravenous (i.v.) Administration of Volasertib. (NCT00804856)
Timeframe: Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
| Intervention | millilitre/minute (mL/min) (Geometric Mean) |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 1280 |
| Phase I Schedule A. Volasertib 200 mg+LDAC | 972 |
| Phase I Schedule A. Volasertib 250 mg+LDAC | 864 |
| Phase I Schedule A. Volasertib 300 mg+LDAC | 1150 |
| Phase I Schedule A. Volasertib 350 mg+LDAC | 1000 |
| Phase I Schedule A. Volasertib 400 mg+LDAC | 852 |
| Phase I Schedule B. Volasertib 150 mg | 1330 |
| Phase I Schedule B. Volasertib 200 mg | NA |
| Phase I Schedule B. Volasertib 350 mg | 810 |
| Phase I Schedule B. Volasertib 400 mg | 1120 |
| Phase I Schedule B. Volasertib 450 mg | 920 |
| Phase I Schedule B. Volasertib 500 mg | 1140 |
| Phase I Schedule B. Volasertib 550 mg | 939 |
| Phase II Schedule A. Volasertib 350 mg+LDAC. | 897 |
Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals
ECG (Electro Cardio Gram) Measurements: Absolute QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) Corrected for Heart Rate Using Fridericia's Formula) Intervals. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol. (NCT00804856)
Timeframe: Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.
| Intervention | milliseconds (ms) (Mean) |
|---|
| Individual baseline | 1 hour after start of infusion | 24 hour after start of infusion |
|---|
| Phase I Schedule B. Volasertib 450 mg | 412.4 | 441.1 | 411.9 |
,| Phase I+II Volasertib 350 mg+LDAC | 411.6 | 430.0 | 414.0 |
Best Eastern Co-operative Oncology Group (ECOG) Performance Score From Baseline Until End of Treatment
ECOG performance score change from baseline to last visit of last cycle = ECOG performance score at last visit of the last cycle - ECOG performance score at baseline. ECOG performance score changes from baseline were also categorised on a 3-point categorical scale: deteriorated (-1), unchanged (0), and improved (1). The number of participants for category of ECOG score change is reported. (NCT00804856)
Timeframe: Baseline and End of Treatment (up to 869 days).
| Intervention | Participants (Count of Participants) |
|---|
| Unchanged | Improved | Deteriorated |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 3 | 0 | 1 |
,| Phase I Schedule A. Volasertib 200 mg+LDAC | 1 | 2 | 0 |
,| Phase I Schedule A. Volasertib 250 mg+LDAC | 5 | 0 | 0 |
,| Phase I Schedule A. Volasertib 300 mg+LDAC | 2 | 1 | 2 |
,| Phase I Schedule A. Volasertib 350 mg+LDAC | 5 | 0 | 3 |
,| Phase I Schedule A. Volasertib 400 mg+LDAC | 1 | 0 | 1 |
,| Phase I Schedule B. Volasertib 150 mg | 9 | 0 | 1 |
,| Phase I Schedule B. Volasertib 200 mg | 1 | 0 | 1 |
,| Phase I Schedule B. Volasertib 350 mg | 0 | 1 | 4 |
,| Phase I Schedule B. Volasertib 400 mg | 4 | 1 | 1 |
,| Phase I Schedule B. Volasertib 450 mg | 14 | 3 | 5 |
,| Phase I Schedule B. Volasertib 500 mg | 2 | 1 | 2 |
,| Phase I Schedule B. Volasertib 550 mg | 3 | 0 | 0 |
,| Phase II Schedule A. Volasertib 350 mg+LDAC | 15 | 13 | 11 |
,| Phase II Schedule C. LDAC | 22 | 8 | 12 |
,| Total Phase I Combined. Schedule A. | 17 | 3 | 7 |
,| Total Phase I Comined. Schedule B. | 33 | 6 | 14 |
,| Total Phase II. Schedule A and C. | 37 | 21 | 23 |
Best Overall Response
"CR~CR+CRi~Partial remission: CR except bone marrow (BM) contained ≥5% but <25% blasts (or ≤50% initial blasts), or <5% blasts in presence of Auer rods or abnormal morphology.~No change: survived ≥7 days (d) after 1st cycle with persistent leukemia in last peripheral blood smear or BM, or with persistent extramedullary disease, without further deterioration due to leukemia or increase of blasts in BM or peripheral blood.~Aplasia: survived ≥7d after 1st cycle, died whilst cytopenic, with last post-treatment BM result aplastic or hypoplastic and without leukemia blasts.~Indeterminate: survived <7 d after 1st cycle or survived ≥7d after 1st cycle, died with no persistent leukemia in peripheral smear but no post-treatment BM examination or did not complete 1st cycle.~Progressive disease: survived ≥7d after 1st cycle with increase of blast population in BM or peripheral blood or aggravation or new extramedullary disease or further deterioration or death due to leukemia." (NCT00804856)
Timeframe: The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.
| Intervention | Participants (Count of Participants) |
|---|
| Complete remission | CRi | Partial remission | No change | Aplasia | Indeterminate | Progressive disease | Not evaluable | Missing |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 0 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 |
,| Phase I Schedule A. Volasertib 200 mg+LDAC | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
,| Phase I Schedule A. Volasertib 250 mg+LDAC | 2 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 |
,| Phase I Schedule A. Volasertib 300 mg+LDAC | 0 | 1 | 0 | 1 | 0 | 2 | 3 | 1 | 1 |
,| Phase I Schedule A. Volasertib 350 mg+LDAC | 0 | 1 | 0 | 1 | 0 | 3 | 3 | 0 | 0 |
,| Phase I Schedule A. Volasertib 400 mg+LDAC | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 |
,| Phase I Schedule B. Volasertib 150 mg | 0 | 0 | 0 | 4 | 0 | 1 | 6 | 0 | 0 |
,| Phase I Schedule B. Volasertib 200 mg | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
,| Phase I Schedule B. Volasertib 350 mg | 0 | 1 | 1 | 2 | 0 | 0 | 1 | 0 | 0 |
,| Phase I Schedule B. Volasertib 400 mg | 0 | 2 | 0 | 2 | 1 | 0 | 1 | 0 | 0 |
,| Phase I Schedule B. Volasertib 450 mg | 0 | 2 | 2 | 7 | 3 | 0 | 7 | 2 | 0 |
,| Phase I Schedule B. Volasertib 500 mg | 0 | 0 | 0 | 3 | 1 | 0 | 1 | 0 | 0 |
,| Phase I Schedule B. Volasertib 550 mg | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 |
,| Phase II Schedule A. Volasertib 350 mg+LDAC | 6 | 7 | 2 | 15 | 0 | 5 | 7 | 0 | 0 |
,| Phase II Schedule C. LDAC | 3 | 3 | 2 | 18 | 0 | 3 | 14 | 2 | 0 |
,| Total Phase I Combined. Schedule A. | 2 | 4 | 0 | 8 | 0 | 6 | 10 | 1 | 1 |
,| Total Phase I Combined. Schedule B. | 0 | 5 | 4 | 18 | 6 | 1 | 19 | 3 | 0 |
,| Total Phase II Combined. Schedule A and C. | 9 | 10 | 4 | 33 | 0 | 8 | 21 | 2 | 0 |
Phase I Schedule A: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles
Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. (NCT00804856)
Timeframe: From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 615 days.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 1 | 1 | 1 |
,| Phase I Schedule A. Volasertib 200 mg+LDAC | 0 | 3 | 0 |
,| Phase I Schedule A. Volasertib 250 mg+LDAC | 0 | 5 | 0 |
,| Phase I Schedule A. Volasertib 300 mg+LDAC | 1 | 5 | 3 |
,| Phase I Schedule A. Volasertib 350 mg+LDAC | 2 | 3 | 2 |
,| Phase I Schedule A. Volasertib 400 mg+LDAC | 1 | 1 | 1 |
,| Total Phase I Combined. Schedule A. | 5 | 18 | 7 |
Phase I Schedule A: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1
Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. (NCT00804856)
Timeframe: First treatment cycle, up to 28 days.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Phase I Schedule A. Volasertib 150 mg+LDAC | 0 | 2 | 0 |
,| Phase I Schedule A. Volasertib 200 mg+LDAC | 0 | 3 | 0 |
,| Phase I Schedule A. Volasertib 250 mg+LDAC | 1 | 3 | 0 |
,| Phase I Schedule A. Volasertib 300 mg+LDAC | 1 | 5 | 3 |
,| Phase I Schedule A. Volasertib 350 mg+LDAC | 2 | 3 | 2 |
,| Phase I Schedule A. Volasertib 400 mg+LDAC | 1 | 1 | 1 |
,| Total Phase I Combined. Schedule A. | 5 | 17 | 6 |
Phase I Schedule B: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles
Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. (NCT00804856)
Timeframe: From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 597 days.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Phase I Schedule B. Volasertib 150 mg | 5 | 4 | 2 |
,| Phase I Schedule B. Volasertib 200 mg | 0 | 1 | 1 |
,| Phase I Schedule B. Volasertib 350 mg | 1 | 3 | 0 |
,| Phase I Schedule B. Volasertib 400 mg | 0 | 5 | 0 |
,| Phase I Schedule B. Volasertib 450 mg | 3 | 15 | 3 |
,| Phase I Schedule B. Volasertib 500 mg | 0 | 1 | 2 |
,| Phase I Schedule B. Volasertib 550 mg | 0 | 3 | 1 |
,| Total Phase I Schedule B. | 9 | 32 | 9 |
Phase I Schedule B: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1
Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. (NCT00804856)
Timeframe: First treatment cycle, up to 28 days.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Phase I Schedule B. Volasertib 150 mg | 5 | 4 | 1 |
,| Phase I Schedule B. Volasertib 200 mg | 0 | 1 | 1 |
,| Phase I Schedule B. Volasertib 350 mg | 1 | 3 | 0 |
,| Phase I Schedule B. Volasertib 400 mg | 0 | 4 | 0 |
,| Phase I Schedule B. Volasertib 450 mg | 5 | 14 | 2 |
,| Phase I Schedule B. Volasertib 500 mg | 0 | 1 | 1 |
,| Phase I Schedule B. Volasertib 550 mg | 0 | 3 | 1 |
,| Total Phase I Schedule B. | 11 | 30 | 6 |
Phase II: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles
Number of patients with AEs following in the in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. (NCT00804856)
Timeframe: From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 890 days.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 | Grade 4 | Grade 5 |
|---|
| Phase II Schedule A. Volasertib 350 mg+LDAC | 12 | 20 | 8 |
,| Phase II Schedule C. LDAC | 13 | 13 | 6 |
QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change From Baseline at Cycle 1
ECG Measurements: QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) changes from baseline at each time point: The QTcF post baseline measurement obtained at time t minus baseline QTcF measurement. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol. (NCT00804856)
Timeframe: Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.
| Intervention | millisecond (ms) (Mean) |
|---|
| Change from baseline after 1 hour | Change from baseline after 24 hour |
|---|
| Phase I Schedule B. Volasertib 450 mg | 29.6 | -0.5 |
,| Phase I+II, Volasertib 350 mg+LDAC | 18.5 | 1.9 |
All-Cause Mortality
Outcome measured for total population. Not broken down by indication received. (NCT01294449)
Timeframe: 5 years
| Intervention | participants (Number) |
|---|
| MADIT-CRT ICD | 11 |
| MADIT-CRT CRT-D | 12 |
Participants With a Complete Response
Complete Response (CR) was defined as: Neutrophil count ≥ 1.0 ×109/L, Platelet count ≥ 100 ×109/L, Bone marrow aspirate ≤5% blasts and No extramedullary leukemia. Response evaluation following Induction Therapy (Cycle 1) and every 2-3 cycles during Consolidation Therapy (Cycles 2 - 7) where Cycle is 4-6 weeks. (NCT01019317)
Timeframe: Minimally 6 weeks (Cycle 1) up to 1 year (7 cycles)
| Intervention | Participants (Number) |
|---|
| Cytarabine + Fludarabine | 34 |
All Cause Mortality
Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality (NCT01191801)
Timeframe: 30 Days
| Intervention | percentage of Participants in the Group (Number) |
|---|
| Group A (Vosaroxin/Cytarabine) | 7.9 |
| Group B (Placebo/Cytarabine) | 6.6 |
All Cause Mortality
Vosaroxin + cytarabine mortality versus placebo + cytarabine mortality (NCT01191801)
Timeframe: 60 Days
| Intervention | percentage of Participants (Number) |
|---|
| Group A (Vosaroxin/Cytarabine) | 19.7 |
| Group B (Placebo/Cytarabine) | 19.4 |
Complete Remission (CR) Rate Based on Modified International Working Group (IWG) Criteria.
Group A (Vosaroxin + cytarabine) patient CR as compared to Group B (placebo + cytarabine) patient CR. Complete remission (CR) is typically defined using IWG criteria as bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts. (NCT01191801)
Timeframe: Up to 5 years or duration of study
| Intervention | percentage of particpants (Number) |
|---|
| Group A (Vosaroxin/Cytarabine) | 30.1 |
| Group B (Placebo/Cytarabine) | 16.3 |
Event Free Survival (EFS)
(NCT01191801)
Timeframe: Up to 5 years or duration of study
| Intervention | months (Median) |
|---|
| Group A (Vosaroxin/Cytarabine) | 1.9 |
| Group B (Placebo/Cytarabine) | 1.3 |
Leukemia-Free Survival (LFS)
Durability of remission (CR) assessed by LFS (NCT01191801)
Timeframe: Up to 5 years or the duration of the study
| Intervention | Months (Median) |
|---|
| Group A (Vosaroxin/Cytarabine) | 11 |
| Group B (Placebo/Cytarabine) | 8.7 |
Overall Remission (OR) Rate Based on the IWG Response Criteria
"Group A patient OR compared to Group B patient OR~Overall Remission includes Complete Remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with incomplete blood count recovery (CRi), and Partial Remission (PR). Complete remission means bone marrow blast count of less than 5% with adequate recovery of peripheral blood counts as typically defined by the IWG. Both CRi and CRp refer complete remission but with incomplete blood count and platelet recovery, respectively. PR, or partial remission, refers to remission in which bone marrow contains blast counts between 5 and 25 percent." (NCT01191801)
Timeframe: Up to 5 years or the duration of the study
| Intervention | percentage of participants (Number) |
|---|
| Group A (Vosaroxin/Cytarabine) | 37.9 |
| Group B (Placebo/Cytarabine) | 18.9 |
Overall Survival
Vosaroxin + cytarabine patient survival versus placebo + cytarabine patient survival (NCT01191801)
Timeframe: Up to 5 years or duration of study
| Intervention | Months (Median) |
|---|
| Group A (Vosaroxin/Cytarabine) | 7.5 |
| Group B (Placebo/Cytarabine) | 6.1 |
Incidence of Acute Graft-versus-host Disease (GVHD)
(NCT00691015)
Timeframe: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 44.7 |
Incidence of Chronic GVHD.
(NCT00691015)
Timeframe: Within 2 years after PBSCT
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 44.68 |
Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders)
(NCT00691015)
Timeframe: Within 6 months after PBSCT
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 80.85 |
Karnofsky Performance Status Performance Status
"100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs.~50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.~20 - Very sick; hospital admission necessary; active supportive treatment necessary.~10 - Moribund; fatal processes progressing rapidly. 0 - Dead" (NCT00691015)
Timeframe: At 90 days after PBSCT
| Intervention | units on a scale (Median) |
|---|
| All Participants | 80 |
Overall Survival.
(NCT00691015)
Timeframe: At 2 years after PBSCT
| Intervention | percentage of participants (Number) |
|---|
| All Participants | 57.4 |
Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment.
(NCT00691015)
Timeframe: Within 6 months after PBSCT
| Intervention | % of participants with a reported SAE (Number) |
|---|
| All Participants | 93.62 |
Severity of Acute Graft-versus-host Disease (GVHD)
(NCT00691015)
Timeframe: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
| Intervention | % of participants with severe aGVHD (Number) |
|---|
| All Participants | 33.3 |
Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] )
(NCT00691015)
Timeframe: post transplant, up to 4 weeks
| Intervention | Days (Median) |
|---|
| All Participants | 11 |
Complete Remission Rate: Percentage of Participants With Complete Remission (CR)
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10^9/L, a platelet count ≥100 × 10^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to <100 × 10^9/L. Partial remission (PR) was defined as a bone marrow with >5% and <25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR. (NCT00669877)
Timeframe: After two 21-day courses, response to treatment checked for Complete Remission (CR)
| Intervention | percentage of participants (Number) |
|---|
| Hyper-CVAD | 85 |
Overall Response Rate: Percentage of Participants With Complete Remission (CR) or Partial Remission (PR)
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10^9/L, a platelet count ≥100 × 10^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to <100 × 10^9/L. Partial remission (PR) was defined as a bone marrow with >5% and <25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR. (NCT00669877)
Timeframe: After two 21-day courses, response to treatment checked for Complete Remission (CR)
| Intervention | percentage of participants (Number) |
|---|
| Hyper-CVAD | 89 |
Days Platelets Count of < 100K/μL
The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle. (NCT00299182)
Timeframe: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
| Intervention | days (Mean) |
|---|
| Arm A 1mcg/kg | 5.5 |
| Arm A 3mcg/kg | 5.3 |
| Arm A 10mcg/kg | 8.3 |
| Arm B 1mcg/kg | 6.8 |
| Arm B 3mcg/kg | 8 |
| Arm B 10mcg/kg | 9.3 |
| Placebo | 9.8 |
Platelet (PLT) Nadir
Blood counts were performed at least two times a week and when clinically indicated during the study and daily when PLT count is < 50K/μL until recovery (two consecutive counts showing upward trend). The optimal biologic dose was defined as the dose of AMG 531 at which the greatest proportion of patients avoided grade 4 thrombocytopenia (Platelet nadir < 25K/μL) in the absence of platelet transfusion in the blinded study cycle. (NCT00299182)
Timeframe: Prior to start of treatment and then at least 2 times a week during treatment until end of cycle 2 (1 cycle = 21 days)
| Intervention | K/μL (Mean) |
|---|
| Arm A 1mcg/kg | 20.3 |
| ARM A 3mcg/kg | 26.3 |
| Arm A 10mcg/kg | 24.8 |
| Arm B 1mcg/kg | 22.5 |
| Arm B 3mcg/kg | 18.3 |
| Arm B 10mcg/kg | 8 |
| Placebo | 11.3 |
Progression Free Survival (PFS) at 7 Months
Progression-free survival defined as time from date of randomization to first occurrence of having documented disease progression or death due to any cause, whichever comes first. Progression based on tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants were followed from baseline to disease progression with PFS evaluation at 7 months. (NCT00656617)
Timeframe: PFS Evaluation at 7 months
| Intervention | percentage of participants (Number) |
|---|
| Idarubicin + Ara-C + Vorinostat | 65 |
Participant Response
Number of participants with response assessed according RECIST: Complete Response (CR) defined as normalization of marrow (< 5% blasts) and of peripheral blood counts (neutrophil count > 1.109/L, platelet count > 100 x 109/L). Partial response (PR) defined as for CR in terms of peripheral counts but with reduction of marrow blasts by >50% compared to pretreatment values but above <5%. Complete Response without platelet recovery (CRp) = CR, but platelets <100 x 109/L. Progressive disease (PD) defined as increase of blasts to > 10% after an initial response. (NCT00656617)
Timeframe: Monitoring with each 4 week cycle, up to 18 cycles of treatment
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Complete Response without platelet recovery (CRp) | Progressive Disease (PD) | No response |
|---|
| Idarubicin + Ara-C + Vorinostat | 67 | 0 | 11 | 0 | 24 |
Progression Free Survival (Rate)
Progression free survival (PFS) for three years following therapy with Rituxan-HCVAD alternating with Rituximab with high -dose methotrexate/ara-C and standard R-CHOP in patients with newly diagnosed B-cell aggressive non-Hodgkin's lymphomas younger than 60 years old and with adjusted IPI 2 or higher adverse prognostic features. (NCT00290498)
Timeframe: 3 years post-therapy
| Intervention | Participants (Count of Participants) |
|---|
| R-HCVAD/MA | 35 |
| R-CHOP | 7 |
Response Rate R-HCVAD vs. R-CHOP
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. (NCT00290498)
Timeframe: 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Complete Remission | Inevaluable | Progressive Disease | Partial Remission | Complete Remission Unconfirmed |
|---|
| R-CHOP | 7 | 1 | 1 | 0 | 1 |
,| R-HCVAD | 40 | 2 | 1 | 4 | 2 |
Percentage of Participants Who Achieve a Timely Engraftment
Timely engraftment is defined as a persistent an absolute neutrophil count (ANC) of at least 500 cells/mm3 and a platelet count of at least 20,000 cells/mm3 for at least 3 days (NCT02797470)
Timeframe: 1 month post-transplant
| Intervention | percentage of participants who achieve a (Mean) |
|---|
| Treatment (Anti-HIV Gene Transduced CD34+ Cells): 1:0 Ratio | 60 |
| Treatment (Anti-HIV Gene Transduced CD34+ Cells): 1:1 Ratio | 75 |
| Treatment (Anti-HIV Gene Transduced CD34+ Cells): 5:1 Ratio | 100 |
Continuous Complete Remission at 1 Year
A patient has a continuous complete remission at 1 year if they achieve a CR and are alive 365 days after registering to the study. (NCT00109837)
Timeframe: After induction, after consolidation, every 3 months during maintenance, and every three months after off treatment for up to a year
| Intervention | participants (Number) |
|---|
| Treatment | 21 |
Toxicity
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00109837)
Timeframe: Patients were assessed for adverse events after the induction cycle
| Intervention | Participants with a given type of AE (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT (serum glut oxaloacetic transaminase) | Albumin, serum-low (hypoalbuminemia) | Alkaline phosphatase | Anorexia | Ascites (non-malignant) | Bilirubin (hyperbilirubinemia) | Calcium, serum-low (hypocalcemia) | Cholecystitis | Cholesterol, serum-high (hypercholesterolemia) | Coagulation-Other (Specify) | Colitis, infectious (e.g., Clostridium difficile) | Constipation | DIC (disseminated intravascular coagulation) | Death not assoc with CTCAE term-Multi-organ fail | Edema: limb | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Fever (in the abs of neutropenia) | Fibrinogen | Glucose, serum-high (hyperglycemia) | Glucose, serum-low (hypoglycemia) | Hemoglobin | Hypertension | Hypotension | Hypoxia | Ileus, GI (functional obstruction of bowel) | Infec(doc clin or mibio) w/ Gr 3/4 neut-Anal | Infec(doc clin or mibio) w/ Gr 3/4 neut-Bladder | Infec(doc clin or mibio) w/ Gr 3/4 neut-Blood | Infec(doc clin or mibio) w/ Gr 3/4 neut-Bronchus | IInfec(doc clin or mibio) w/ Gr 3/4 neut-Catheter | Infec(doc clin or mibio) w/ Gr 3/4 neut-Eye NOS | Infec(doc clin or mibio) w/ Gr 3/4 neut-Lung | Infec(doc clin or mibio) w/ Gr 3/4 neut-Nose | Infec(doc clin or mibio) w/ Gr 3/4 neut-Pharynx | Infec(doc clin or mibio) w/ Gr 3/4 neut-Ur tract | Infec with nor ANC or Gr 1/2 neut-Lung (pneumonia) | Infection-Other (Specify) | Leukocytes (total WBC) | Lipase | Liver dysfunction/failure (clinical) | Lymphopenia | Magnesium, serum-high (hypermagnesemia) | Mucositis/stomatitis (clinical exam) - Oral cavity | Mucositis/stomatitis (funct/symp) - Oral cavity | Mucositis/stomatitis (func/symp) - Pharynx | Muscle weak,gen spec area-Whole body | Nausea | Neuropathy: motor | Neutrophils/granulocytes (ANC/AGC) | Pain - Abdomen NOS | Pain - Bone | Pain - Neck | Pancreatic endocrine: glucose intolerance | Pancreatitis | Phosphate, serum-low (hypophosphatemia) | Platelets | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Rash/desquamation | Renal failure | Sodium, serum-low (hyponatremia) | Thrombosis/thrombus/embolism | Thrombotic microangiopathy | Triglyceride, serum-high (hypertriglyceridemia) | Tumor lysis syndrome | Typhlitis (cecal inflammation) | Uric acid, serum-high (hyperuricemia) | Vomiting |
|---|
| Induction | 17 | 13 | 3 | 2 | 2 | 1 | 6 | 7 | 1 | 2 | 1 | 1 | 1 | 2 | 1 | 1 | 3 | 18 | 1 | 11 | 16 | 1 | 33 | 2 | 3 | 2 | 1 | 1 | 1 | 11 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 2 | 1 | 43 | 1 | 2 | 19 | 1 | 2 | 1 | 1 | 2 | 3 | 1 | 47 | 1 | 1 | 1 | 1 | 1 | 1 | 44 | 1 | 7 | 1 | 2 | 6 | 1 | 2 | 1 | 5 | 1 | 1 | 1 |
Bortezomib Clearance
Median and range of bortezomib clearance during Induction II. (NCT01371981)
Timeframe: Day 8 of Induction II
| Intervention | Liters/hour/m^2 (Median) |
|---|
| Arm B | 8.42 |
Change in Ejection Fraction
The mean percentage change in ejection fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. (NCT01371981)
Timeframe: Up to 4 weeks
| Intervention | Percentage change (Mean) |
|---|
| Arm A | -2.0272 |
| Arm B | -2.3453 |
| Arm C (Cohort 1) | -7.5000 |
| Arm C (Cohort 2) | -5.1997 |
| Arm C (Cohort 3) | -3.4624 |
Change in Shortening Fraction
Mean percentage change in shortening fraction from baseline to the end of Induction I will be determined for eligible patients enrolled on Arms A, B and C. (NCT01371981)
Timeframe: Up to 4 weeks
| Intervention | Percentage change (Mean) |
|---|
| Arm A | -1.8445 |
| Arm B | -2.6298 |
| Arm C (Cohort 1) | -2.2333 |
| Arm C (Cohort 2) | -3.6700 |
| Arm C (Cohort 3) | -3.4246 |
EFS for Patients on Arm C, Cohort 1
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 1) | 25.00 |
EFS for Patients on Arm C, Cohort 2
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 2) | 56.12 |
EFS for Patients on Arm C, Cohort 3
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 3) | 58.18 |
Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm A | 45.64 |
| Arm B | 46.95 |
OS for Patients on Arm C, Cohort 1
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 1) | 41.67 |
OS for Patients on Arm C, Cohort 2
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 2) | 64.77 |
OS for Patients on Arm C, Cohort 3
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm C (Cohort 3) | 61.84 |
Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm A | 65.04 |
| Arm B | 68.45 |
Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II
The proportion of high risk children without HR FLT3/ITD+ converting from positive MRD at end of Induction I to negative MRD at the end of Induction II will be estimated as well as the corresponding 95% confidence interval determined using a binomial exact method. (NCT01371981)
Timeframe: Up to 8 weeks
| Intervention | Proportion of patients (Number) |
|---|
| Arm A | 0.5000 |
| Arm B | 0.5238 |
Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy
The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). (NCT01371981)
Timeframe: Up to 2 years
| Intervention | Proportion of patients (Number) |
|---|
| Arm A | 0.8819 |
| Arm B | 0.9217 |
| Arm C (Cohort 1) | 0.9167 |
| Arm C (Cohort 2) | 0.9394 |
| Arm C (Cohort 3) | 0.9149 |
| Arm D | 0.0239 |
Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
Cumulative incidence estimates 3 year relapse rate defined as time from study entry to induction failure or relapse where deaths or secondary malignancies are competing events. (NCT01371981)
Timeframe: Up to 3 years
| Intervention | percentage of patients (Number) |
|---|
| Arm A | 46.67 |
| Arm B | 46.65 |
Sorafenib Steady State Concentration
Median and range of sorafenib steady state concentration for Induction I. (NCT01371981)
Timeframe: Up to 30 days
| Intervention | Nanogram/Milliliter (Median) |
|---|
| Arm C | 1090.0 |
Total Scale Score From Parent-reported Cancer Module
"Results represent the total scale scores from the parent report of the PedsQL™ 3.0 Cancer Module for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. Scores on a scale is used for a unit of measure." (NCT01371981)
Timeframe: Up to 14 days
| Intervention | Scores on a scale (Mean) |
|---|
| Arm A | 66.2 |
| Arm B | 65.8 |
| Arm C (Cohort 1) | 74.9 |
| Arm C (Cohort 2) | 63.7 |
Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module
"Results represent the total scale scores from the parent report of the PedsQL™ Multidimensional Fatigue Scale for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. Scores on a scale is used for a unit of measure." (NCT01371981)
Timeframe: Up to 14 days
| Intervention | Scores on a scale (Mean) |
|---|
| Arm A | 60.5 |
| Arm B | 58.1 |
| Arm C (Cohort 1) | 71.2 |
| Arm C (Cohort 2) | 48.2 |
Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module
"Results represent the total scale scores from the parent report of the PedsQL™ 4.0 Generic Core Scales for timepoint 1 (up to 14 days from start of therapy). Items are reverse-scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Therefore, a higher number is a better outcome. The total score is the sum of all the items divided by the number of items answered on all the scales. Scores on a scale is used for a unit of measure." (NCT01371981)
Timeframe: Up to 14 days
| Intervention | Scores on a scale (Mean) |
|---|
| Arm A | 68.3 |
| Arm B | 67.8 |
| Arm C (Cohort 1) | 71.3 |
| Arm C (Cohort 2) | 61.6 |
Early Marrow Status (EMS) by MRD Status End Induction (Day 29)
Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative) (NCT00103285)
Timeframe: Early Marrow Status at Day 15, MRD Status at Day 29 of therapy.
| Intervention | Participants (Count of Participants) |
|---|
| All Patients for Induction, MRD Negative | 4378 |
| All Patients for Induction, MRD Positive | 258 |
Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative)
Event-free probability where EFS is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: 6 years
| Intervention | Percent probability (Number) |
|---|
| Group 1-SR-low ALL, Arm I-combination Chemotherapy | 95.22 |
| Group 2-SR-avg ALL, Arm I-combination Chemotherapy | 88.52 |
Event-free Survival (EFS) for SR-High Patients.
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: 6 years
| Intervention | percent probability (Number) |
|---|
| Group 3-SR-high ALL, Combination Chemotherapy | 85.58 |
Event-free Survival (EFS) for SR-Low Patients
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: 6 years
| Intervention | Percent probability (Number) |
|---|
| SR-low ALL, Arm I-combination Chemotherapy | 95.22 |
| SR-low ALL, Arm II-combination Chemotherapy | 93.96 |
Event-Free Survival Probability According to MRD Status End Induction (Day 29)
Event-Free survival by Day 29 MRD status (negative vs positive), Event Free Probability (time from study entry to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: MRD at Day 29 of therapy
| Intervention | Percent Probability (Number) |
|---|
| Induction Therapy, MRD Negative | 91.39 |
| Induction Therapy, MRD Positive | 79.86 |
Overall Survival Probability (OS) According to Induction Day 29 MRD Status
Overall survival by Day 29 MRD status (negative vs positive), Overall survival defined as time from study entry to death or date of last contact for patients who are alive. (NCT00103285)
Timeframe: Overall Survival Probability of 6 years
| Intervention | percent probability (Number) |
|---|
| Induction Therapy, MRD Negative | 97.07 |
| Induction Therapy, MRD Positive | 90.47 |
Event-free Survival (EFS) for SR-Average ALL Patients
EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: 6 years
| Intervention | percent probability (Number) |
|---|
| Standard and Intensified therapy |
|---|
| Group 2-SR-avg ALL, Arm III-combination Chemotherapy | 88.34 |
,| Group 2-SR-avg ALL, Arm IV-combination Chemotherapy | 90.51 |
Event-free Survival (EFS) for SR-Average ALL Patients
EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. (NCT00103285)
Timeframe: 6 years
| Intervention | percent probability (Number) |
|---|
| Standard and Intensified therapy | Standard therapy |
|---|
| Group 2-SR-avg ALL, Arm I-combination Chemotherapy | 83.82 | 87.41 |
,| Group 2-SR-avg ALL, Arm II-combination Chemotherapy | 88.89 | 88.29 |
Health-related Quality of Life Relative to Physical, Social and Emotional Impairment
To identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.Standardized scores will be computed for child function using the gender and age-adjusted scores available from normative data from a healthy population of about 10,000 children. The various domains of family functioning will be assessed using well-validated instruments and analyzed as a dichotomous variable (impaired vs. non-impaired family functioning). Multiple regression analysis will be used to test the effect of family functioning (adjusted for therapy given, age at diagnosis, gender, socioeconomic status and other factors) on child function. (NCT00103285)
Timeframe: At 1, 6 and 12 months after diagnosis and, 3 months post-therapy
| Intervention | Percentage of participants (Number) |
|---|
| Physical Impairment 1 mth after diagnosis | Physical Impairment 6 mths after diagnosis | Physical Impairment 12 mths after diagnosis | Physical Impairment 3 mths post therapy | Social Impairment 1 mth after diagnosis | Social Impairment 6 mths after diagnosis | Social Impairment 12 mths after diagnosis | Social Impairment 3 mths post-therapy | Emotional Impairment 1 mth after diagnosis | Emotional Impairment 6 mths after diagnosis | Emotional Impairment 12 mths after diagnosis | Emotional Impairment 3 mths post-therapy |
|---|
| Induction Therapy | 76.39 | 42.75 | 29.41 | 27.84 | 43.36 | 23.66 | 23.53 | 25.77 | 38.89 | 17.56 | 13.97 | 8.25 |
Optimal Time Point for Advance Health Related Quality of Life Intervention
Percentage of patients with elevated Anxiety. (NCT00103285)
Timeframe: At 1 month after diagnosis and 3 months post-therapy.
| Intervention | Percentage of participants (Number) |
|---|
| At 1 month after diagnosis | At 3 months post-therapy |
|---|
| Induction Therapy | 25.2 | 24.0 |
Disease Free Survival
Participants are followed after completion of protocol therapy until disease progression to determine disease free survival. (NCT00126191)
Timeframe: Until disease progression up to 120 months
| Intervention | Months (Mean) |
|---|
| Low Risk | 84 |
| High Risk | 52 |
Response Rates (CR and PR) in Adults With Burkitt/Atypical Burkitt
"Complete Response (CR): Disappearance of all measurable or evaluable disease confirmed.~Partial Response (PR): Reduction of 50% or greater in the sum of the products of the perpendicular diameters of all measurable.~Of 8 High Risk participants, 7 met the primary response outcome. 1 High Risk participant did not meet protocol defined primary outcome response and died two months following enrollment." (NCT00126191)
Timeframe: 3 years
| Intervention | participants (Number) |
|---|
| Low Risk | 2 |
| High Risk | 7 |
Duration of Event-free Survival
Event-free survival was measured as date of randomization until treatment failure. Treatment failure was defined as failure to achieve composite completed morphological remission during the induction and re-induction phase of the study lasting up to 60 days, relapse from complete response, or death from any cause, whichever occurred first. (NCT02873338)
Timeframe: Randomization up to 30 months
| Intervention | days (Median) |
|---|
| Control (Idarubicin+Cytarabine) | 243.5 |
| Dociparstat 0.125 mg/kg | 1 |
| Dociparstat 0.25 mg/kg | 171.5 |
Duration of Morphologic Complete Remission
"The duration of morphologic complete remission was assessed only in subjects who had achieved morphologic complete remission and was defined as the time from achievement of complete response to the detection or relapse. Relapse was defined as the reappearance of leukemia blasts in the peripheral blood, >5% blasts in the bone marrow not attributable to another cause, or appearance/reappearance of extramedullary disease and with a bone marrow blast percentage of >5% but ≤20%. If the latter, a repeat bone marrow examination was performed at least 7 days after the first marrow examination; documentation of the bone marrow blast percentage of >5% was necessary to establish relapse. Assessments were performed every 3 months and continued until death or 18 months after the last subject was randomized, whichever occurred first.~Duration of morphologic complete remission (time from the achievement of complete response to the detection of relapse)" (NCT02873338)
Timeframe: Randomization to end of study (18 months)
| Intervention | days (Median) |
|---|
| Control (Idarubicin+Cytarabine) | 233 |
| Dociparstat 0.125 mg/kg | 494 |
| Dociparstat 0.25 mg/kg | 294 |
Number of Subjects Who Achieved Composite Complete Remission
The composite complete remission (CR) rate included CR, CR without recovery of platelets (CRp), and CR without recovery of neutrophils and/or platelets (CRi), as defined by the International Working Group criteria during the induction and re-induction phases of treatment. CR was defined as an Absolute Neutrophil Count (ANC) >1000/μL, platelet count >100,000/μL, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. CRi was defined as an ANC <1000/μL and/or platelet count <100,000/, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. (NCT02873338)
Timeframe: Up to 60 days after the start of each treatment cycle
| Intervention | Participants (Count of Participants) |
|---|
| Control (Idarubicin+Cytarabine) | 16 |
| Dociparstat 0.125 mg/kg | 9 |
| Dociparstat 0.25 mg/kg | 15 |
Number of Subjects Who Achieved Morphologic Complete Remission
Morphologic complete remission (CR) was evaluated by International Working Group (IWG) criteria and defined as absolute neutrophil count (ANC) >1000/microliter; platelet count >100,000, <5% blasts in bone marrow aspirate, no blasts with Auer rods, and no evidence of extramedullary disease. (NCT02873338)
Timeframe: During induction and re-induction phases of treatment (up to 60 days after the start of each treatment cycle)
| Intervention | Participants (Count of Participants) |
|---|
| Control (Idarubicin+Cytarabine) | 14 |
| Dociparstat 0.125 mg/kg | 8 |
| Dociparstat 0.25 mg/kg | 11 |
Number of Subjects Who Died by Day 30
Mortality (rate of death) of subjects by Day 30, measured from the first day of induction treatment to 30 days post-induction. (NCT02873338)
Timeframe: 30 days (from first day of induction treatment to 30 days after)
| Intervention | Participants (Count of Participants) |
|---|
| Control (Idarubicin+Cytarabine) | 2 |
| Dociparstat 0.125 mg/kg | 1 |
| Dociparstat 0.25 mg/kg | 3 |
Number of Subjects Who Died by Day 60.
Mortality (rate of death) of subjects by Day 60, measured from the first day of induction treatment to 60 days post-induction. (NCT02873338)
Timeframe: 60 days (from the first day of induction treatment to 60 days after)
| Intervention | Participants (Count of Participants) |
|---|
| Control (Idarubicin+Cytarabine) | 2 |
| Dociparstat 0.125 mg/kg | 2 |
| Dociparstat 0.25 mg/kg | 3 |
Number of Subjects Who Died by Day 90
Mortality (rate of death) of subjects at Day 90, measured from the first day of induction treatment to 90 days post-induction. (NCT02873338)
Timeframe: 90 days (from the first day of induction treatment to 90 days after)
| Intervention | Participants (Count of Participants) |
|---|
| Control (Idarubicin+Cytarabine) | 2 |
| Dociparstat 0.125 mg/kg | 3 |
| Dociparstat 0.25 mg/kg | 3 |
Time to Leukemia-free Survival
Leukemia-free survival was assessed as a secondary endpoint only in subjects who achieved composite complete remission and was measured from randomization until disease relapse or death from any cause, whichever occurred first. Assessments were performed every 3 months until death or 18 months after the last subject was randomized, whichever occurred first. (NCT02873338)
Timeframe: Randomization until disease relapse or patient death from any cause, whichever occurs first, assessed up to 30 months
| Intervention | days (Median) |
|---|
| Control (Idarubicin+Cytarabine) | 292 |
| Dociparstat 0.125 mg/kg | 448 |
| Dociparstat 0.25 mg/kg | 166 |
Time to Platelet Recovery
Platelet recovery was measured from randomization to platelet recovery (platelet count >20,000/µL and >100,000/µL) (NCT02873338)
Timeframe: Randomization to platelet recovery, for up to 60 days after the start of each treatment cycle
| Intervention | days (Median) |
|---|
| Recovery to >20,000µL | Recovery to >100,000µL |
|---|
| Control (Idarubicin+Cytarabine) | 35 | 38 |
,| Dociparstat 0.125 mg/kg | 36 | 50 |
,| Dociparstat 0.25 mg/kg | 29 | 32 |
Time to Recovery of Neutrophils
Neutrophil recovery was assessed from randomization to Absolute Neutrophil Count (ANC) recovery (ANC >500/µL and >1000/µL) for up to 60 days after the start of each treatment cycle. (NCT02873338)
Timeframe: Randomization to ANC recovery, for up to 60 days after the start of each treatment cycle
| Intervention | days (Median) |
|---|
| Recovery to >500/µL | Recovery to >1000/µL |
|---|
| Control (Idarubicin+Cytarabine) | 32 | 37 |
,| Dociparstat 0.125 mg/kg | 43 | 42 |
,| Dociparstat 0.25 mg/kg | 29 | 35 |
Percentage of Participants With Continuous Complete Remission of Patients Receiving High-dose and Conventional Dose PEG-asparaginase.
"The primary objective of this study is to compare the distributions of continuous complete remission of patients randomized on the first day of the continuation phase to receive a higher dose of PEG-asparaginase or to receive the conventional dose (2,500 units/m2).~The randomization will occur on the starting day of the continuation phase, at which time all information necessary for performing the randomization should be available. In the rare case that immunophenotype and/or Day-15 MRD is not available, we will make the following assumptions: If immunophenotype is unknown at the time the randomization is to be executed, then it will be assumed B-lineage. If Day-15 MRD is unknown at the time of randomization, then it will be assumed negative (<0.01%). Past experience indicate that few patients will fall into these unknown categories." (NCT00549848)
Timeframe: 3.5 years after the last enrollment up to 12.5 years
| Intervention | Percentage of participants (Number) |
|---|
| PEG 3500 Units/m^2 | 91.6 |
| PEG 2500 Units/m^2 | 90.7 |
Probability of CNS Relapse
To assess whether intensification of CNS-directed intrathecal and systemic chemotherapy will improve outcome in patients at high-risk of CNS relapse. (NCT00549848)
Timeframe: For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years
| Intervention | Percentage of participants (Number) |
|---|
| TOTXVI PEG 3500 | 0.8 |
| TOTXVI PEG 2500 | 1.8 |
| TOTXVI Not Randomized | 2.7 |
| All Eligible Patients in TOTXV | 5.7 |
Probability of Event-free Survival
"To estimate the event-free survival of children with ALL who are treated with risk-directed therapy and to compare the EFS results of TOTXVI with that of TOTXV (NCT00137111).~EFS will be measured from the date of complete response to the date of initial failure for patients who fail. Failure includes the traditional endpoints of failure to achieve a complete remission, relapse in any site, secondary malignancy, and death during induction or remission. EFS time will be measured to the date of last contact for patients who are failure free at the time of analysis. The EFS time is defined to be zero (0) for patients who die during induction therapy or fail to achieve a complete remission." (NCT00549848)
Timeframe: For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years
| Intervention | Percentage of participants (Number) |
|---|
| TOTXVI PEG 3500 | 92.4 |
| TOTXVI PEG 2500 | 91.1 |
| TOTXVI Not Randomized | 86.3 |
| All Eligible Patients in TOTXV | 87.1 |
Probability of Overall Survival
To estimate the overall survival of children with ALL who are treated with risk-directed therapy and to compare the EFS results of TOTXVI with that of TOTXV. (NCT00549848)
Timeframe: For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years
| Intervention | Percentage of participants (Number) |
|---|
| TOTXVI PEG 3500 | 97.5 |
| TOTXVI PEG 2500 | 95.6 |
| TOTVI Not Randomized | 90.8 |
| All Eligible Patients in TOTXV | 93.5 |
Proportion of Participants With Minimal Residual Disease (MRD) at End of Remission Induction ≥ 0.01%
To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD ≥ 5% will result in improved leukemia cytoreduction in this subgroup compared to therapy followed in the TOTXV protocol. (NCT00549848)
Timeframe: End of remission induction; day 42 in Total XVI and day 46 in Total XV
| Intervention | Participants (Count of Participants) |
|---|
| TOTXVI PEG 3500 | 7 |
| TOTXVI PEG 2500 | 12 |
| TOTXVI Not Randomized | 20 |
| All Eligible Patients in TOTXV | 44 |
Proportion of Participants With Minimal Residual Disease (MRD) on the 15th Day of Remission Induction ≥ 5%
To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD ≥ 5% will result in improved leukemia cytoreduction in this subgroup compared to therapy followed in the TOTXV protocol. (NCT00549848)
Timeframe: Middle of remission induction, Day 15 in Total XVI and Day 19 in Total XV
| Intervention | Participants (Count of Participants) |
|---|
| TOTXVI PEG 3500 | 22 |
| TOTXVI PEG 2500 | 26 |
| TOTXVI Not Randomized | 31 |
| All Eligible Patients in TOTXV | 55 |
Event-free Survival Rate
Proportion of patients who were event free at 4 months (NCT00098839)
Timeframe: At 4 months after enrollment
| Intervention | Proportion of participants (Number) |
|---|
| Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly | .604 |
| Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly | .640 |
Pharmacokinetics
Mean trough serum concentration measured before final dose of epratuzumab. (NCT00098839)
Timeframe: Up to day 36
| Intervention | ug/mL (Mean) |
|---|
| Twice Weekly Dosing Schedule | 501 |
Rate of Minimal Residual Disease (MRD) < 0.01%
Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD < 0.01%. (NCT00098839)
Timeframe: At the end of Block 1 of re-induction therapy (day 36)
| Intervention | Proportion of participants (Number) |
|---|
| Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly | .195 |
| Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly | .295 |
Remission Re-induction (CR2) Rate
The proportion of patients who achieved complete response at the end Block 1 of re-induction therapy. Complete Remission (CR) - Attainment of M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC >1000/uL and platelet count >100,000/uL). Partial Remission (PR) - Complete disappearance of circulating blasts and achievement of M2 marrow status (5% or < 25% blast cells and adequate cellularity). Partial Remission Cytolytic (PRCL) - Complete disappearance of circulating blasts and achievement of at least 50% reduction from baseline in bone marrow blast count. Minimal Response Cytolytic (MRCL) - 50% reduction in the peripheral blast count with no increase in peripheral white blood cell count. (NCT00098839)
Timeframe: At the end of Block 1 of re-induction therapy (day 36)
| Intervention | proportion of participants (Number) |
|---|
| Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly | .646 |
| Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly | .660 |
Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)
Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose. (NCT00541866)
Timeframe: From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.
| Intervention | Participants (Count of Participants) |
|---|
| Sch A, Cohort 10mg/m2 | 0 |
| Sch A, Cohort 20mg/m2 | 0 |
| SchA, Cohort 34mg/m2 | 0 |
| Sch A, Cohort 50mg/m2 | 0 |
| Sch A, Cohort 70mg/m2 | 1 |
| Sch A, Cohort 80mg/m2 | 1 |
| Sch A, Cohort 90mg/m2 | 2 |
| Sch B, Cohort 70 mg/m2 | 0 |
| Sch B, Cohort 80mg/m2 | 1 |
| Sch B, Cohort 90mg/m2 | 1 |
Leukemia-free Survival (LFS)
Leukemia-free survival is censored at the last known alive date without report of relapse. (NCT00541866)
Timeframe: From time of the start of CR or CRp to the earliest date of relapse, commencement of reinduction therapy, or death, assessed monthly up to 2 years after the end of study visit.
| Intervention | months (Median) |
|---|
| Group 1 (Sch A, 10 to 90 mg/m2) | 12.0 |
| Group 2 (Sch B, 70 to 90 mg/m2): | 4.7 |
| Group 3 (Sch A, First Relapse, 80 mg/m2): | 7.4 |
| Group 4 (Sch B, First Relapse, 90 mg/m2) | 25.2 |
| Group 5 (Sch B, Primary Refractory, 90 mg/m2): | NA |
Overall Survival
Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died. (NCT00541866)
Timeframe: Time between the date of first study treatment and the date of death due to any cause for upto 2 years after the end of study visit
| Intervention | months (Median) |
|---|
| Group 1 (Sch A, 10 to 90 mg/m2) | 4.1 |
| Group 2 (Sch B, 70 to 90 mg/m2): | 8.0 |
| Group 3 (Sch A, First Relapse, 80 mg/m2): | 4.1 |
| Group 4 (Sch B, First Relapse, 90 mg/m2) | 7.1 |
| Group 5 (Sch B, Primary Refractory, 90 mg/m2): | 5.9 |
Remission Rates (CR+CRp)
"Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator.~CR is defined as >1000 Neutrophils (ul), >100,000 Platelets (uL) and <5 BM Blasts (%); CRp is defined as >1000 Neutrophils (ul), <=100,000 Platelets (uL) and <5 BM Blasts (%); CRi is defined as >1000 Neutrophils (ul), <100,000 Platelets (uL) and <5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse." (NCT00541866)
Timeframe: Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 (Sch A, 10 to 90 mg/m2) | 9 |
| Group 2 (Sch B, 70 to 90 mg/m2): | 4 |
| Group 3 (Sch A, First Relapse, 80 mg/m2): | 7 |
| Group 4 (Sch B, First Relapse, 90 mg/m2) | 3 |
| Group 5 (Sch B, Primary Refractory, 90 mg/m2): | 4 |
| Total | 27 |
All Cause Mortality
Mortality of those patients enrolled in the study and receiving intervention (NCT00541866)
Timeframe: 30 and 60 days
| Intervention | Participants (Count of Participants) |
|---|
| 30 Days | 60 Days |
|---|
| Group 1 (Sch A, 10 to 90 mg/m2) | 8 | 10 |
,| Group 2 (Sch B, 70 to 90 mg/m2): | 0 | 2 |
,| Group 3 (Sch A, First Relapse, 80 mg/m2) | 1 | 2 |
,| Group 4 (Sch B, First Relapse, 90 mg/m2) | 0 | 1 |
,| Group 5 (Sch B, Primary Refractory, 90 mg/m2) | 1 | 1 |
Minimal Residual Disease
The presence or absence of tumor cells at the end of induction assessed by studying tissue and/or blood/marrow. Details of methods and criteria used can be found in Shiramizu at al. BJH 153:758-763, 2011 (full citation in the citation section). (NCT00057811)
Timeframe: Not Provided
| Intervention | percentage of samples analyzed (Number) |
|---|
| Group B (Chemotherapy, Protective Therapy, Monoclonal Antib.) | 22 |
| Group C (Chemotherapy, Monoclonal Antibody Therapy) | 70 |
Response Rate
Response includes both complete and partial responses. Per protocol, complete Response is defined as the complete disappearance of all clinical evidence of disease by physical examination, by imaging studies, by bone marrow biopsy (where indicated), by CNS evaluation (where indicated) and by biopsy where there is a residual abnormality on an imaging study. Bone marrow must contain <5% blasts. CSF WBC must be <5/μL with no blasts or lymphomatous cells present. Partial response is defined as: at least a 50% reduction in the size of all measurable tumor areas. Each site is to be defined by the product of the maximum length, width and depth (3 dimensions). No lesion may progress. No new lesion may appear. Bone marrow must contain <5% blasts. CSF WBC must be <5/μL with no blasts or lymphomatous cells present.. (NCT00057811)
Timeframe: Up to 5 years
| Intervention | percentage of participants analyzed (Number) |
|---|
| Group B (Chemotherapy, Protective Therapy, Monoclonal Antib.) | 88 |
| Group C (Chemotherapy, Monoclonal Antibody Therapy) | 83 |
Grade ≥ 3 Stomatitis
The incidence of grade ≥ 3 stomatitis. Grade 3 stomatitis: Confluent ulcerations or pseudomembranes; bleeding with minor trauma. Grade 4 stomatitis: Tissue necrosis; Significant spontaneous bleeding; life-threatening consequences (NCT00057811)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Incidence of grade ≥ 3 stomatitis | No incidence of grade ≥ 3 stomatitis |
|---|
| Group B (Chemotherapy, Protective Therapy, Monoclonal Antib.) | 4 | 41 |
,| Group C (Chemotherapy, Monoclonal Antibody Therapy) | 6 | 34 |
Toxic Death
Implementation of the toxic death rate stopping rule, a death must be possibly, probably or definitely attributable to Rituximab and/or chemotherapy to be considered a toxic death. (NCT00057811)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Toxic death | No toxic death |
|---|
| Group B (Chemotherapy, Protective Therapy, Monoclonal Antib.) | 0 | 45 |
,| Group C (Chemotherapy, Monoclonal Antibody Therapy) | 2 | 38 |
Disease-free Survival, for Only Complete Response Patients
Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented. (NCT00061945)
Timeframe: 9 years 4 months
| Intervention | months (Median) |
|---|
| Phase I - Alemtuzumab and Combination Chemotherapy | 58.6 |
| Phase II - Alemtuzumab and Combination Chemotherapy | 19.8 |
Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)
The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data. (NCT00061945)
Timeframe: 6 weeks
| Intervention | mg (Number) |
|---|
| Phase I - Alemtuzumab and Combination Chemotherapy | 30 |
Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II)
Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative. (NCT00061945)
Timeframe: 9 years 4 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase II - Alemtuzumab and Combination Chemotherapy | 16 |
Number of Participants Achieving Complete Remission
A complete remission (CR) requires the following: an absolute neutrophil count (segs and bands) > 1500/μl, no circulating blasts, platelets > 100,000/μl; bone marrow cellularity > 20% with trilineage hematopoiesis, and < 5% marrow blast cells, none of which appear neoplastic. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement). (NCT00061945)
Timeframe: 9 years
| Intervention | participants (Number) |
|---|
| Phase I - Alemtuzumab and Combination Chemotherapy | 92 |
| Phase II - Alemtuzumab and Combination Chemotherapy | 145 |
Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II)
The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV. (NCT00061945)
Timeframe: 8 months
| Intervention | participants (Number) |
|---|
| Phase II - Alemtuzumab and Combination Chemotherapy | 30 |
Overall Survival
Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented. (NCT00061945)
Timeframe: 9 years 4 months
| Intervention | months (Median) |
|---|
| Phase I - Alemtuzumab and Combination Chemotherapy | 33.6 |
| Phase II - Alemtuzumab and Combination Chemotherapy | 23.1 |
Number of Patients Experiencing Adverse Events.
Number of patients experiencing adverse events during the course of protocol therapy. (NCT00450801)
Timeframe: Up to 5 years
| Intervention | participants (Number) |
|---|
| R-MACLO Cycles | 22 |
| R-IVAM Cycles | 22 |
| Thalidomide Therapy | 19 |
Response Rate
Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement. (NCT00450801)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| R-MACLO-IVAM-T | 100 |
Overall Survival Rate
Percentage of participants who are alive up to five years after receipt of protocol therapy. (NCT00450801)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| 1-year rate overall survival Rate | 2-year overall survival Rate | 3-year overall survival rate | 4-year overall survival rate | 5-year overall survival rate |
|---|
| R-MACLO-IVAM-T | 96 | 96 | 96 | 87 | 87 |
Progression-free Survival Rate
Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion. (NCT00450801)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| 1 year progression-free survival | 3 year progression-free survival | 5-year progression-free survival |
|---|
| R-MACLO-IVAM-T | 91 | 78 | 69 |
Event-free Survival
Assessed by time to treatment failure, occurrence of second malignant neoplasm, or death from any cause. Statistical analysis will be to estimate the difference in the proportion of patients treated with each therapy who are long-term event-free survivors due either to the difference between the backbone therapy regimens (CCG BFM vs NHL/BFM-95), or due to the intensification. (NCT00004228)
Timeframe: 5 years
| Intervention | percentage of particpants (Number) |
|---|
| A0 (Localized Disease Stg I/II) Modified CCG BFM | 88 |
| A1 (Disseminated, No CNS - CCG Mod BFM w/Out Intens | 82 |
| A2 (Disseminated, No CNS - CCG Mod BFM w/ Intens | 80 |
| B2 (CNS+) NHL/BFM-95 w/Intens Delayed Radiation Therapy | 63 |
| B2 (Disseminated,CNS- (< Amend 7B)) NHL/BFM-95 w/Intens | 82 |
| B1 (Disseminated CNS-) NHL/BFM-95 w/Out Intens | 84 |
| B1 (NHL/BFM-95 w/Out Intens) Additional Enrollment | 90 |
Percentage of Patients With Overall Survival as Assessed by Time to Death
Overall survival will be computed by measuring the rate of deaths during induction due primarily to treatment toxicity and cumulative incidence of toxic deaths in induction or deaths in remission overall and separately for treatment groups defined by the two design factors. (NCT00004228)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| A0 (Localized Disease Stg I/II) Modified CCG BFM | 96 |
| A1 (Disseminated, No CNS - CCG Mod BFM w/Out Intens | 84 |
| A2 (Disseminated, No CNS - CCG Mod BFM w/Intens | 88 |
| B2 (CNS+) NHL/BFM-95 w/Intens Delayed Radiation Therapy | 81 |
| B2 (Disseminated,CNS- (< Amend 7B)) NHL/BFM-95 w/Intens | 85 |
| B1 (Disseminated CNS-) NHL/BFM-95 w/Out Intens | 85 |
| B1 (NHL/BFM-95 w/Out Intens) Additional Enrollment | 92 |
Complete Remission
Complete remission (CR) is defined as: <5% marrow aspirate blasts. Blasts can be >=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils >= 1000/mcl; platelets >100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be <=100,000/mcl and/or ANC may be <1,000/mcl. (NCT00945815)
Timeframe: After induction therapy was completed (1 or 2 months)
| Intervention | percentage of participants (Number) |
|---|
| Ara-C + Clofarabine + Epratuzumab | 52 |
Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. (NCT00945815)
Timeframe: Up to 5 years
| Intervention | Participants (Number) |
|---|
| Abdominal pain | Acute kidney injury | Alanine aminotransferase increased | Alkaline phosphatase increased | Anemia | Anorexia | Aspartate aminotransferase increased | Cardiac arrest | Catheter related infection | Diarrhea | Electrocardiogram QT corrected interval prolonged | Encephalopathy | Enterocolitis infectious | Febrile neutropenia | Gum infection | Hepatic failure | Hypercalcemia | Hyperglycemia | Hyperkalemia | Hypertension | Hypocalcemia | Hypokalemia | Hyponatremia | Hypophosphatemia | Hypotension | Hypoxia | Infections and infestations-Gram neg. bacteremia | Investigations - Bacteremia | Leukocytosis | Lung infection | Lymphocyte count decreased | Nervous system disorders - subdural hematoma | Neutrophil count decreased | Oral pain | Platelet count decreased | Respiratory failure | Sepsis | Tooth infection | Tumor lysis syndrome | Typhlitis | White blood cell decreased |
|---|
| Ara-C + Clofarabine + Epratuzumab | 1 | 1 | 5 | 1 | 6 | 1 | 6 | 2 | 2 | 2 | 1 | 2 | 2 | 17 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 2 | 1 | 1 | 1 | 4 | 4 | 1 | 9 | 1 | 12 | 1 | 4 | 1 | 1 | 2 | 8 |
Event Free Survival (EFS)
Time from date of treatment start until the date of first objective documentation of disease-relapse. (NCT03634228)
Timeframe: Up to 3 years, 4 months
| Intervention | Months (Median) |
|---|
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 0 | 1.9 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 1 | 2.4 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 2 | 1.8 |
Maximum Tolerated Dose (MTD) (Phase I)
As determined by dose limiting toxicity (DLT). MTD is defined the highest dose at which no more than one patient out of 6 patients experience DLTs in the first cycle. A 3+3 algorithm will be applied for dose escalation or dose de-escalation. (NCT03634228)
Timeframe: Up to 28 days
| Intervention | Milligrams (Number) |
|---|
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) | 260 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT03634228)
Timeframe: Up to 3 years, 4 months
| Intervention | Months (Median) |
|---|
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 0 | 2.1 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 1 | 4.3 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 2 | 7.6 |
Participants With a Response
Response is Complete Response (CR) + Complete Response with Incomplete Blood Count Recovery (CRi) + Partial Response (PR) + Morphologic Leukemia -Free State (MLFS: CR is Bone marrow blasts < 5%; absence of circulating blasts and blasts with Auer rods; absence of extra-medullary disease; ANC >/= 1.0 x 10^9/L; platelet count >/= 100 x 10^9/L. CRi is CR except for ANC < 1.0 x 10^9 or platelet count , 100 x 10^9/L. PR is decreased bone marrow blast % by at least 50% to a value of 5% to 25% and ANC >/= 1.0 x 10^9/L; platelet count >/= 100 x 10^9/L. MLFS is Bone marrow blasts < 5%; abcence of blasts with Auer rods; absence of extra-medullary disease; no hematologic recovery required. (NCT03634228)
Timeframe: Up to 3 years, 4 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 0 | 0 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 1 | 1 |
| Phase I (Low Dose Cytarabine, MDM2 Inhibitor DS-3032b) Cohort 2 | 1 |
Disease-free Survival (Consolidation Phase)
Disease-free survival is defined from the time of the confirmation of a complete remission via biopsy to the relapse of the disease. (NCT00049517)
Timeframe: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter.
| Intervention | Months (Median) |
|---|
| Autologous HCT | 15.0 |
| Go/Autologous HCT | 13.6 |
Overall Survival (Consolidation Phase)
Overall survival is defined as the time from randomization in the consolidation phase to death. (NCT00049517)
Timeframe: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter.
| Intervention | Months (Median) |
|---|
| Autologous HCT | 35.5 |
| Go/Autologous HCT | 27.9 |
Overall Survival (Induction Phase)
Overall survival is defined as the time from randomization in the induction phase to death. (NCT00049517)
Timeframe: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until 5 years after study entry and every 12 months thereafter.
| Intervention | months (Median) |
|---|
| Standard Daunorubicin | 15.7 |
| High-dose Daunorubicin | 23.7 |
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who discontinued study treatment due to an AE is summarized. (NCT00907517)
Timeframe: Up to 135 days
| Intervention | Participants (Number) |
|---|
| MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 140 mg + Cytarabine 2 g/m^2 | 0 |
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0). DLTs in Cycle 1 consisted of any of the following: 1) Selected Grade 4 drug-related nonhematologic toxicities, 2) Selected Grade 3 drug-related nonhematologic toxicities that do not resolve to ≤ Grade 2 within 48 hours: Neurotoxicity of any duration, Nephrotoxicity of any duration, QT interval corrected by Fridericia (QTcF) prolongation of any duration, 3) Inability to administer Day 10 cytarabine therapy due to ongoing, uncontrolled serious or life-threatening toxicity. The number of participants who experienced a DLT during Cycle 1 is summarized. (NCT00907517)
Timeframe: Throughout Cycle 1 (Up to 6 weeks)
| Intervention | Participants (Number) |
|---|
| MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2 | 0 |
| MK-8776 140 mg + Cytarabine 2 g/m^2 | 3 |
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who experienced an AE is summarized. (NCT00907517)
Timeframe: Up to 45 days after last dose of study treatment (Up to 180 days)
| Intervention | Participants (Number) |
|---|
| MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2 | 3 |
| MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2 | 3 |
| MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2 | 6 |
| MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2 | 6 |
| MK-8776 140 mg + Cytarabine 2 g/m^2 | 6 |
Complete Remission Rate (CR) + CR With Incomplete Recovery (CRi)
Expansion from phase II pilot to a phase II trial will depend on demonstration of CR/CRi amongst 4 of the initial 10 treated patients. Investigators will measure remission rate at day 28 to address the primary endpoint of complete remission (with or without complete hematologic recovery), as defined by Cheson Criteria (ref 27). For those with extramedullary disease, Lugano criteria will be used to assess response. This is a standard assessment of drug efficacy for phase 2 clinical trial design in acute leukemias, as response correlates closely with progression free- and overall survival (PFS and OS). (NCT03575325)
Timeframe: At day 28
| Intervention | Percent of participants (Number) |
|---|
| CPX-351 Treatment | 30 |
Overall Survival (OS)
Overall Survival as defined by Cheson and Lygano Criteria, namely death due to any cause as assessed from time of first treatment. Overall Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment. (NCT03575325)
Timeframe: 12 months
| Intervention | Days (Median) |
|---|
| CPX-351 Treatment | 218 |
Progression Free Survival (PFS)
Progression Free Survival as defined by Cheson and Lugano Criteria, namely progression, failure to respond, or death, as assessed from time of first treatment. Progression Free Survival will be reported as per Cheson Criteria, and analyzed using a standard Kaplan-Meier approach. Patients will undergo bone marrow biopsy evaluation after each cycle of therapy per standard of care to facilitated assessment. (NCT03575325)
Timeframe: 12 months
| Intervention | Days (Median) |
|---|
| CPX-351 Treatment | 57 |
Event Free Survival
Percentage of patients who were event free at 4 months (NCT00873093)
Timeframe: 4 months after enrollment
| Intervention | Percentage of participants (Number) |
|---|
| Pre-B ALL Relapse 18-36 Mths From Dx (Chemotherapy)Age<=21 Yrs | 68.5 |
| Pre-B ALL Relapse <18 Mths From Dx (Chemotherapy) Age <=21 Yrs | 37.8 |
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 1. (NCT00873093)
Timeframe: End of Block 1 (Day 36 of Block 1) of re-induction therapy
| Intervention | percentage of participants (Number) |
|---|
| Pre-B ALL Relapse 18-36 Mths From Dx (Chemotherapy)Age<=21 Yrs | 35.4 |
| Pre-B ALL Relapse <18 Mths From Dx (Chemotherapy) Age <=21 Yrs | 25 |
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 2
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 2. (NCT00873093)
Timeframe: End of Block 2 (Day 36 of Block 2) of re-induction therapy
| Intervention | percentage of participants (Number) |
|---|
| Pre-B ALL Relapse 18-36 Mths From Dx (Chemotherapy)Age<=21 Yrs | 66.7 |
| Pre-B ALL Relapse <18 Mths From Dx (Chemotherapy) Age <=21 Yrs | 42.1 |
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3
Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 3. (NCT00873093)
Timeframe: End of Block 3 (Day 36 of Block 3) of re-induction therapy
| Intervention | Percentage of participants (Number) |
|---|
| Pre-B ALL Relapse 18-36 Mths From Dx (Chemotherapy)Age<=21 Yrs | 80 |
| Pre-B ALL Relapse <18 Mths From Dx (Chemotherapy) Age <=21 Yrs | 63.6 |
Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy
The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy. (NCT00873093)
Timeframe: The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy.
| Intervention | Percentage of participants (Number) |
|---|
| Pre-B ALL Relapse 18-36 Mths From Dx (Chemotherapy)Age<=21 Yrs | 72.2 |
| Pre-B ALL Relapse <18 Mths From Dx (Chemotherapy) Age <=21 Yrs | 63 |
Severe Adverse Events (SAE) Rate.
The proportion of SAE rate among all eligible patients (NCT00873093)
Timeframe: 4 months
| Intervention | percentage of participants (Number) |
|---|
| Overall | 8.2 |
Toxic Death Rate
The proportion of toxic death rate among all eligible patients. (NCT00873093)
Timeframe: 4 months
| Intervention | percentage of participants (Number) |
|---|
| Overall | 2.1 |
Area Under the Curve of LY2181308 Over the Dosing Interval
Area under the curve of LY2181308 over the dosing interval (NCT00620321)
Timeframe: Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
| Intervention | nanograms*hour/milliliter (ng*h/mL) (Geometric Mean) |
|---|
| LY2181308 | 216947 |
| LY2181308 + Idarubicin + Cytarabine | 185734 |
Change From Baseline in Survivin Index at Day 2
Data presented are the ratio of Day 2 survivin index to the baseline survivin index. Survivin is a protein expressed in tumor cells, including acute myeloid leukemia (AML), which regulates mitosis and prevents tumor cell death. Survivin index was calculated as ([blast survivin mean equivalent fluorochrome (MEFL) - blast isotypic control MEFL]/blast isotypic control MEFL). (NCT00620321)
Timeframe: Baseline, Day 2
| Intervention | ratio (Least Squares Mean) |
|---|
| LY2181308 | 0.43 |
Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)
Response is complete remission (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) + cytoreduction. CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L. PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR). Response rate is calculated as a total number of participants with CR or CRi or PR or cytoreduction divided by the total number of participants treated multiplied by 100. (NCT00620321)
Timeframe: Baseline to progression of disease or death up to 6 months
| Intervention | percentage of participants (Number) |
|---|
| LY2181308 | 0 |
| LY2181308 + Idarubicin + Cytarabine | 56.3 |
Pharmacodynamics: Number of Participants With Survivin Protein Expression
Pharmacodynamics: Number of participants with Survivin Protein Expression. (NCT00620321)
Timeframe: 6 Months
| Intervention | Participants (Count of Participants) |
|---|
| LY2181308 | 2 |
Number of Participants Who Died Due to Progressive Disease or Unknown Cause During the 21 Days Post Study Treatment Follow-Up
Deaths due to progressive disease (PD) and unknown cause are not considered adverse events. Deaths due to PD and unknown cause occurring during the 21-day follow-up period after treatment discontinuation are reported here and for those occurring while participants were on treatment are reported in the Participant Flow. Deaths due to serious adverse events occurred during the study including the 21-day follow-up period are reported in the Reported Adverse Events section. (NCT00620321)
Timeframe: Study treatment discontinuation up to 21 days post study treatment discontinuation
| Intervention | Participants (Count of Participants) |
|---|
| Death due to progressive disease | Death due to unknown cause |
|---|
| LY2181308 | 1 | 1 |
,| LY2181308 + Idarubicin + Cytarabine | 0 | 0 |
Number of Participants With Adverse Events (Safety Profile)
Data are presented as number of participants who experienced serious adverse events (SAE) and possibly drug-related treatment-emergent adverse events (TEAE) during the study including the 21-day follow-up period. A summary of serious adverse events and other nonserious adverse events regardless of causality is located in the Reported Adverse Events section. (NCT00620321)
Timeframe: Start of treatment to study completion up to 6.7 months
| Intervention | Participants (Count of Participants) |
|---|
| SAE | Drug-related TEAE |
|---|
| LY2181308 | 6 | 2 |
,| LY2181308 + Idarubicin + Cytarabine | 13 | 11 |
Disease Free Survival(DFS) Rate
Disease free survival time is defined for all evaluable patients who have achieved a CR or CRi as the time from registration to relapse or death due to any cause. The distribution of disease-free survival will be estimated using the method of Kaplan-Meier. (NCT01806571)
Timeframe: 35 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Nilotinib, Daunorubicin Hydrochloride, Cytarabine) | 56.4 |
Duration of Complete Response
The distribution of duration of complete response will be estimated using the method of Kaplan-Meier. (NCT01806571)
Timeframe: 2 years
| Intervention | Months (Median) |
|---|
| Treatment (Nilotinib, Daunorubicin Hydrochloride, Cytarabine) | NA |
Incidence of Adverse Events as Assessed by NCI CTCAE Version 4.0
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. This data will be reported in the Adverse Events section of the results. (NCT01806571)
Timeframe: 35 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Nilotinib, Daunorubicin Hydrochloride, Cytarabine) | 34 |
Overall Survival(OS) Rate
Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier(Kaplan E 1958). (NCT01806571)
Timeframe: 39 Months
| Intervention | percentage of patients alive (Number) |
|---|
| Treatment (Nilotinib, Daunorubicin Hydrochloride, Cytarabine) | 70.6 |
Proportion of Complete Responses (CR or CRi) During Induction Therapy
The proportion of successes will be estimated 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. (NCT01806571)
Timeframe: Up to 56 days
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Nilotinib, Daunorubicin Hydrochloride, Cytarabine) | 0.618 |
Days to Engraftment of Lymphocytes
Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3). (NCT00520130)
Timeframe: 2 years
| Intervention | Days (Median) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 16 |
| B - Cyclosporine (AC Arm) | 76 |
Days to Engraftment of Neutrophils
Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3). (NCT00520130)
Timeframe: 2 years
| Intervention | Days to neutrophil engraftment (Median) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 11 |
| B - Cyclosporine (AC Arm) | 9 |
Days to Engraftment of Platelets
Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support (NCT00520130)
Timeframe: 2 years
| Intervention | Days (Median) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 19 |
| B - Cyclosporine (AC Arm) | 14 |
Early Treatment Related Mortality
Any death occurring within 28 days after transplantation in a patient in continuous remission. (NCT00520130)
Timeframe: Less than or equal to 28 days after transplantation
| Intervention | participants (Number) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 1 |
| B - Cyclosporine (C) Arm | 0 |
Overall Survival
Time between the first day of transplant to the day of death. (NCT00520130)
Timeframe: Patients were followed for an average of up to 5 years.
| Intervention | Months (Median) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 41.7 |
| B - Cyclosporine (AC) Arm | 18.8 |
Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)
Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria. (NCT00520130)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 42 |
| B - Cyclosporine (AC) Arm | 38 |
Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)
Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria. (NCT00520130)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 13 |
| B - Cyclosporine (AC) Arm | 21 |
Percentage of Participants With Late Treatment Related Mortality
Any death occurring 28 days or more after transplantation in a patient in continuous remission. (NCT00520130)
Timeframe: Greater than 28 days after transplantation
| Intervention | percentage of participants (Number) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 28 |
| B - Cyclosporine (AC) Arm | 29 |
Toxicities
Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. (NCT00520130)
Timeframe: 103 months and 22 days
| Intervention | participants (Number) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 43 |
| B - Cyclosporine (AC) Arm | 42 |
Changes in CD8 T Cell Receptor Vbeta Repertoire
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison. (NCT00520130)
Timeframe: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
| Intervention | Divergence index (Median) |
|---|
| 1 month | 3 months | 6 mo (TMS=7; AC= 9) | 12 mo (TMS=7; AC= 9) | Donor CD8 cells (TMS=8; AC= 8) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 62 | 54 | 62 | 55 | 47 |
,| B - Cyclosporine (AC) Arm | 78 | 81 | 84 | 89 | 43 |
Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire
Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison. (NCT00520130)
Timeframe: Donor at time of collection and recipient at 1, 3, 6 and 12 months post transplant
| Intervention | Divergence index (Median) |
|---|
| 1 month | 3 months | 6 mo (TMS=7; AC= 9) | 12 mo (TMS=7; AC=9) | Donor CD4 cells (TMS=8; AC=8) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 48 | 31 | 35 | 30 | 23 |
,| B - Cyclosporine (AC) Arm | 90 | 66 | 75 | 67 | 22 |
Immune Reconstitution of Cluster of Differentiation 4 (CD4) T Cell Populations
Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count. (NCT00520130)
Timeframe: 2 weeks, and 1, 3, 6, 12 and 24 months post transplant
| Intervention | Cells/µl (Median) |
|---|
| 2 weeks | 1 month | 3 months | 6 months | 12 months | 24 months |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 171 | 285 | 297 | 387 | 447 | 451 |
,| B - Cyclosporine (AC) Arm | 0 | 21 | 61 | 121 | 132 | 373 |
Immune Reconstitution of Cluster of Differentiation 8 (CD8) T Cell Populations
Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count. (NCT00520130)
Timeframe: 2 weeks, 1, 3, 6, 12 and 24 months post transplant
| Intervention | Cells/µl (Median) |
|---|
| 2 weeks | 1 month | 3 months | 6 months | 12 months | 24 months |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 72 | 204 | 334 | 429 | 485 | 434 |
,| B - Cyclosporine (AC) Arm | 1 | 6 | 54 | 158 | 243 | 502 |
Immune Reconstitution of Normal Killer (NK) Cells
Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count. (NCT00520130)
Timeframe: 2 weeks, and 1, 3, 6, 12, and 24 months post transplant
| Intervention | Cells/µl (Median) |
|---|
| 2 weeks | 1 month | 3 months | 6 months | 12 months | 24 months |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 123 | 270 | 134 | 136 | 134 | 133 |
,| B - Cyclosporine (AC) Arm | 15 | 31 | 124 | 202 | 150 | 307 |
Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)
Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria. (NCT00520130)
Timeframe: 2 years post transplant
| Intervention | percentage of participants (Number) |
|---|
| Moderate or Severe cGVHD | Severe cGVHD |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 50 | 28 |
,| B - Cyclosporine (AC) Arm | 12 | 5 |
Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells
The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry. (NCT00520130)
Timeframe: Recipient recovery at 6, 12 and 24 months post transplant
| Intervention | % of naive (CCR7+CD45RA+) CD4 Cells (Median) |
|---|
| 6 mo (TMS=28; AC= 28) | 12 mo (TMS=25; AC= 21) | 24 mo (TMS=18; AC= 13) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 24 | 22 | 20 |
,| B - Cyclosporine (AC) Arm | 1 | 7 | 25 |
Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells
The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry. (NCT00520130)
Timeframe: Recipient recovery at 6, 12 and 24 months post transplant
| Intervention | % of naive (CCR7+CD45RA+) CD8 Cells (Median) |
|---|
| 6 mo (TMS=28; AC= 28) | 12 mo (TMS=25; AC= 21) | 24 mo (TMS=18; AC= 13) |
|---|
| A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm | 20 | 17 | 16 |
,| B - Cyclosporine (AC) Arm | 3 | 6 | 6 |
Overall Survival
(NCT00512252)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Phase II Dose Treatment | 37 |
Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 <= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity. (NCT00512252)
Timeframe: Completion of all patients in Phase I portion (232 days)
| Intervention | mcg/kg (Number) |
|---|
| Phase I Dose Escalation | 240 |
Relapse-free Survival
"This is determined only for patients achieving a complete remission. Defined as the interval from the date of the first documentation of a leukemia free state to date of recurrence or death due to any cause.~Kaplain-Meier estimate was used." (NCT00512252)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Phase II Dose Treatment | 42.9 |
Time to Neutrophil Recovery
Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count >1,000 cells/mm^3. (NCT00512252)
Timeframe: 42 days
| Intervention | days (Median) |
|---|
| Phase II Dose Treatment | 28 |
Time to Platelet Recovery
Defined as the date of the first dose of AMD3100 to the date that the platelet count is >100,000/mm3 in the absence of platelet transfusions. (NCT00512252)
Timeframe: 42 days
| Intervention | days (Median) |
|---|
| Phase II Dose Treatment | 28.5 |
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0. (NCT00512252)
Timeframe: Day 0
| Intervention | percentage of AML blasts (Median) |
|---|
| AML blasts at 0 hours | AML blasts at 1 hour | AML blasts at 2 hours | AML blasts at 4 hours | AML blasts at 6 hours | AML blasts at 8 hours | AML blasts at 12 hours | AML blasts at 24 hours |
|---|
| Phase I Dose Escalation - Dose Level 1 | 46.0 | 26.0 | 26.0 | 37.0 | 31.0 | 32.0 | 27.0 | 35.0 |
,| Phase I Dose Escalation - Dose Level 2 | 4.0 | 9.0 | 37.5 | 16.0 | 14.0 | 19.0 | 45.0 | 23 |
,| Phase I Dose Escalation - Dose Level 3 | 43.5 | 30.5 | 32.5 | 30.0 | 27.0 | 26.0 | 35.0 | 55 |
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
"Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.~Characterization of the mobilized cells as well as the kinetics of mobilization will be determined by analyzing the surface expression of mobilized cells by flow cytometry at the specified time points in conjunction with their total leukocyte count from the patient's CBC." (NCT00512252)
Timeframe: Day 0
| Intervention | cells x 10^3/microliter (Median) |
|---|
| Total leukocytes at 0 hours | Total leukocytes at 1 hour | Total leukocytes at 2 hours | Total leukocytes at 4 hours | Total leukocytes at 6 hours | Total leukocytes at 8 hours | Total leukocytes at 12 hours | Total leukocytes at 24 hours |
|---|
| Phase I Dose Escalation - Dose Level 1 | 2.5 | 4.3 | 4 | 4.7 | 4.8 | 4.5 | 5.1 | 4.3 |
,| Phase I Dose Escalation - Dose Level 2 | 4.7 | 7.0 | 8.5 | 9.4 | 11.3 | 12.0 | 12.1 | 7.9 |
,| Phase I Dose Escalation - Dose Level 3 | 3.5 | 6.4 | 7.5 | 8.3 | 9.5 | 8.9 | 7.8 | 5.8 |
Phase II Only: Complete Response Rate of AMD3100 + MEC
"Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response.~Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi)." (NCT00512252)
Timeframe: 42 days
| Intervention | percentage of participants (Number) |
|---|
| CR + CRi | CR only |
|---|
| >= Second Relapse/Salvage | 25 | 25 |
,| First Relapse, First Salvage | 56 | 47 |
,| Primary Refractory | 20 | 20 |
,| Total | 46 | 39 |
Safety and Tolerability of AMD3100 + MEC.
Treatment related mortality (deaths occurring during treatment) (NCT00512252)
Timeframe: 42 days
| Intervention | participants (Number) |
|---|
| Sepsis | Adverse transfusion reaction w/febrile neutropenia |
|---|
| Phase II Dose Treatment | 2 | 1 |
Treatment Failure
Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi. (NCT00512252)
Timeframe: 42 days
| Intervention | participants (Number) |
|---|
| Persistent leukemia | Death during aplasia | Unknown |
|---|
| >= Second Relapse/Salvage | 3 | 0 | 0 |
,| First Relapse, First Salvage | 12 | 1 | 1 |
,| Primary Refractory | 6 | 2 | 0 |
,| Total | 21 | 3 | 1 |
Number of Patients With Complete Remission
Complete remission is defined as: less than 5% bone marrow blasts, neutrophils greater or equal to 1,000 per microliter, platelets greater than 100,000 per microliter, no blasts in the peripheral blood, and no extramedullary disease (NCT00337168)
Timeframe: Between day 28 and day 35 inclusive
| Intervention | participants (Number) |
|---|
| Induction | 3 |
Number of Patients With Very Poor Risk Cytogenetics
(NCT00337168)
Timeframe: On average, 2 weeks before treatment started
| Intervention | participants (Number) |
|---|
| Induction | 10 |
Expression of Nucleoside Transporters
Expression was examined in paraffin-embedded tissue by immunohistochemistry. Intensities were scored on a 0-2+ scale. High expression was a score of 2+. (NCT00337168)
Timeframe: On average, two weeks before treatment started
| Intervention | participants (Number) |
|---|
| High expression of hENT1 | High expression of hCNT3 | High expression of dCK cytoplasmic | High expression of dCK nuclear |
|---|
| Induction | 7 | 6 | 4 | 4 |
Toxicity
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00337168)
Timeframe: Patients were assess for adverse events after each induction cycle (up to two cycles) and after the one consolidation cycle
| Intervention | Participants with a given type of AE (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT (serum glut oxaloacetic transaminase) | Albumin, serum-low (hypoalbuminemia) | Anorexia | Ascites (non-malignant) | Bilirubin (hyperbilirubinemia) | Calcium, serum-low (hypocalcemia) | Colitis | Colitis, infectious (e.g., Clostridium difficile) | Confusion | Creatinine | DIC (disseminated intravascular coagulation) | Death not assoc with CTCAE term-Multi-organ fail | Dermatology/Skin-Other (Specify) | Diarrhea | Dyspnea (shortness of breath) | Edema: limb | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Glucose, serum-high (hyperglycemia) | Hemoglobin | Hypotension | Hypoxia | INR | Infec with Gr 34 neutrophils - Bladder (urin | IInfec with Gr 34 neutrophils - Blood | Infec with Gr 34 neutrophils - Catheter-rela | Infec with Gr 34 neutrophils - Colon | Infec with Gr 34 neutrophils - Conjunctiva | Infec with Gr 34 neutrophils - Larynx | Infec with Gr 34 neutrophils - Lung (pneumon | Infec with Gr 34 neutrophils - Skin (celluli | Infec with Gr 34 neutrophils - Urinary tract | Infec with Gr 34 neutrophils - Wound | Infection with unknown ANC - Lung (pneumonia) | Infection-Other (Specify) | Leukocytes (total WBC) | Liver dysfunction/failure (clinical) | Lymphopenia | Mental status | Neutrophils/granulocytes (ANC/AGC) | PTT (Partial thromboplastin time) | Pain - Abdomen NOS | Pain - Back | Pain - Bone | Platelets | Pleural effusion (non-malignant) | Pneumonitis/pulmonary infiltrates | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Pruritus/itching | Renal failure | Restrictive cardiomyopathy | Sodium, serum-high (hypernatremia) | Sodium, serum-low (hyponatremia) | Supraventricular and nodal arrhythmia | Tumor lysis syndrome | Typhlitis (cecal inflammation) | Uric acid, serum-high (hyperuricemia) |
|---|
| Induction | 5 | 7 | 3 | 1 | 2 | 3 | 1 | 1 | 2 | 1 | 4 | 1 | 1 | 1 | 2 | 1 | 1 | 2 | 14 | 1 | 13 | 3 | 1 | 1 | 1 | 9 | 1 | 2 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 11 | 1 | 7 | 1 | 18 | 1 | 1 | 1 | 1 | 20 | 1 | 1 | 1 | 4 | 1 | 3 | 1 | 1 | 2 | 1 | 1 | 1 | 1 |
Early Post BMT Toxicities
Number of participants who experience organ failure or severe infections (defined as Grade III/IV by NCI CTC for Adverse Events (CTCAE), version 2.0) (NCT00368355)
Timeframe: 100 Days
| Intervention | Participants (Count of Participants) |
|---|
| CLINIMACS Device | 14 |
| ISOLEX Device | 14 |
Engraftment Rate After Transplant
Percentage of participants with hematopoietic engraftment post-transplant. Engraftment is defined as the first day absolute neutrophil counts exceeded 0.5 X 10^9/ml. (NCT00368355)
Timeframe: 28 days
| Intervention | percentage of participants (Number) |
|---|
| CLINIMACS Device | 100 |
| ISOLEX Device | 100 |
Severe GVHD Rate
Percentage of participants with Grade III/IV acute GVHD. Severe GVHD is defined as Grade III/IV acute GVHD. (NCT00368355)
Timeframe: 100 Days
| Intervention | percentage of participants (Number) |
|---|
| CLINIMACS Device | 0 |
| ISOLEX Device | 4.3 |
Disease-free Survival (DFS) Rate at 1 Year
"For participants who achieved a complete remission (CR), this is the percentage of participants who were alive and relapse free at 1 year. The 1 year rate, with 95% confidence interval, was estimated using the Kaplan-Meier method~A CR is defined as those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils > 1000 mL and platelets >= 100,000 mL)." (NCT00416598)
Timeframe: At 1 year
| Intervention | percentage of participants (Number) |
|---|
| Decatibine Maintenance | 80 |
Number of Participants Who Completed Maintenance Decitabine.
To determine feasibility of decitabine maintenance, this outcome measures the number of participants who completed all 8 planned cycles of decitabine maintenance as per protocol. (NCT00416598)
Timeframe: Up to 5 years
| Intervention | participants (Number) |
|---|
| Decatibine Maintenance | 62 |
Event-free Survival (EFS)
EFS - time from study entry until failure to achieve complete remission during consolidation, relapse, or death. For further clarification see definitions provided in the protocol. (NCT00866918)
Timeframe: At 3 years from study entry
| Intervention | Percentage of participants (Number) |
|---|
| Standard Risk | 95.4 |
| High Risk | 82.9 |
Hematologic Remission Rate
Proportion of patients in hematologic remission at end of consolidation, course 1 are reported. (NCT00866918)
Timeframe: End of consolidation, course 1: up to 5 months
| Intervention | Proportion of participants (Number) |
|---|
| Standard Risk | 1.0000 |
| High Risk | 0.8824 |
Hematologic, Molecular, and Cytogenetic Remission Rate
Proportion of patients in hematologic, molecular, and cytogenetic remission at end of consolidation, course 3 and 4 are reported. Patients were determined to be in remission by all three criteria. (NCT00866918)
Timeframe: End of consolidation, course 3; up to 7 months (for Standard Risk) or end of consolidation, course 4; up to 9 months (for High Risk)
| Intervention | Proportion of participants (Number) |
|---|
| Standard Risk | 0.8095 |
| High Risk | 0.5882 |
Overall Survival (OS)
OS - time from study entry to death. (NCT00866918)
Timeframe: At 3 years from study entry
| Intervention | Percentage of participants (Number) |
|---|
| Standard Risk | 98.4 |
| High Risk | 85.7 |
Number of Participants With a 2-Year Progression-Free Survival (PFS)
Response evaluated using the standard criteria response for lymphoma through CT scan. (NCT00591630)
Timeframe: 2 years (beginning day 30 after treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 - Zevalin + BEAM + Rituximab +Stem Cell Transplant | 6 |
| Group 1 - Zevalin + BEAM + Stem Cell Transplant | 8 |
| Group 2 - BEAM + Rituximab + Stem Cell Transplant | 8 |
| Group 2 - BEAM + Stem Cell Transplant | 5 |
Progression Free Survival
Overall Progression Free Survival at 2 years (NCT00594815)
Timeframe: 2 Years
| Intervention | percentage of participants (Number) |
|---|
| Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma | 57 |
Total Number of Participants Who Experienced Acute Treatment Related Adverse Events
The toxicity of this combined regimen will be measured using the NCI CTC version 2.0. (NCT00594815)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma | 52 |
1 Year Progression-free Survival Rate
Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: >50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy. (NCT00577629)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Induction + Consolidation + Bexxar | 0.74 |
Disease-free Survival
Disease-free survival is measured from the date of CR or CRu to date of relapse or death (NCT00577629)
Timeframe: 10 years
| Intervention | months (Mean) |
|---|
| Experimental: Induction + Consolidation + Bexxar | 54.10 |
Overall Response
"Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period.~CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.~PR =~>/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.~No increase should be observed in the size of other nodes, liver, or spleen.~Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.~Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.~Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders.~No new sites of disease should be observed." (NCT00577629)
Timeframe: up to 1 year
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Induction + Consolidation + Bexxar | 92 |
Overall Survival
Overall Survival is measured from the first day of chemotherapy until death from any cause. (NCT00577629)
Timeframe: 10 years
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Induction + Consolidation + Bexxar | 82 |
Secondary Malignancies
The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes. (NCT00577629)
Timeframe: 10 years
| Intervention | Participants (Count of Participants) |
|---|
| Myelodysplastic Syndrome (MDS) | Acute Myeloid Leukemia (AML) | Pancreatic Cancer | Hodgkins Lymphoma | Melanoma | Renal Cell Carcinoma |
|---|
| Experimental: Induction + Consolidation + Bexxar | 3 | 1 | 1 | 1 | 1 | 1 |
Maximum Tolerated Dose [MTD] Determination by Number of Participants With Dose Limiting Toxicity (DLT)
"The Maximum tolerated dose (MTD) was the highest dose level at which fewer than 2 of 6 patients developed a dose limiting toxicity (DLT) in the first two cycles of therapy. A 3 by 3 design was used for dose escalation in the phase I portion of the study.~A dose-limiting toxic effect (DLT) was defined as a clinically significant adverse event or abnormal laboratory value directly attributable to everolimus and assessed as unrelated to disease progression, intercurrent illness, or concomitant medications, occurring during the first or second cycle of therapy, that met any of the following criteria: CTCAE version 3.0 grade 3 increased AST or ALT for 7 days, CTCAE grade 4 increased AST or ALT of any duration, or any other clinically significant CTCAE grade 3 or 4 toxic effect. Electrolyte abnormalities (changes in glucose, chemistries, liver enzymes, pancreatic enzymes) correctable by optimal therapy and without clinical impact were not considered DLTs." (NCT00968253)
Timeframe: Following first two dose cycles (21 days/each), up to 42 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I: RAD001 5 mg + Combination Chemo | 0 |
| Phase I: RAD001 10 mg + Combination Chemo | 1 |
Overall Response Rate (OR) Where OR = CR + CRp + CRi
Number of participants out of total treated who experienced a complete response response according to RECIST criteria either (CR + CRp) CR Without Platelet Recovery. Response (CR + CRp) defined as Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x10^9/L, platelet count > 100 x10^9/L, and blasts < 5% in a normocellular or hypercellular marrow. Complete remission without platelet recovery (CRp): Peripheral blood and marrow parameters as for CR, but with platelet count > 20 x 10^9/L and < 100 x 10^9/L in the absence of platelet transfusions. CR with incomplete blood count recovery (CRi): Same as CR but platelets ≤ 100,000/mcl and/or neutrophils ≤ 1,000/mcl. (NCT00968253)
Timeframe: 8 courses of treatment, up to 24 weeks
| Intervention | percentage of participants (Number) |
|---|
| Phase I: RAD001 5 mg + Combination Chemo | 33 |
| Phase I: RAD001 10 mg + Combination Chemo | 33 |
| Phase II: MTD RAD001 + Combination Chemo | 33 |
Participant Responses by Daily Dose Level Assignment (RAD001 5 mg, 10 mg and MTD 5 mg)
Response defined as Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x10^9/L, platelet count > 100 x10^9/L, and blasts < 5% in a normocellular or hypercellular marrow. Complete remission without platelet recovery (CRp): Peripheral blood and marrow parameters as for CR, but with platelet count > 20 x 10^9/L and < 100 x 10^9/L in the absence of platelet transfusions. CR with incomplete blood count recovery (CRi): Same as CR but platelets ≤ 100,000/mcl and/or neutrophils ≤ 1,000/mcl. Partial remission (PR): Peripheral blood count recovery as for CR, with decrease in marrow blasts by > 50% from pretreatment values with no more than 25% leukemia/lymphoma cells in the marrow. Nonresponder, Other: All other responses will be considered failures. (NCT00968253)
Timeframe: Up to 20 cycles of study drugs (21 day cycles) or till disease progression
| Intervention | participants (Number) |
|---|
| Complete Remission | Complete Remission without platelet recovery | CR with incomplete blood count recovery | Partial Remission | Nonresponder |
|---|
| Phase I: RAD001 10 mg + Combination Chemo | 2 | 0 | 1 | 1 | 5 |
,| Phase I: RAD001 5 mg + Combination Chemo | 1 | 0 | 0 | 1 | 1 |
,| Phase II: MTD RAD001 + Combination Chemo | 3 | 1 | 0 | 0 | 8 |
Number of Participants With Adverse Events (AEs)
Safety and tolerability of sorafenib with DepoCyt. Toxicities were to be reported using tables and descriptive statistics by type and grade. All patients were to be followed up until death. (NCT00964743)
Timeframe: 6 Months
| Intervention | participants (Number) |
|---|
| Intrathecal DepoCyt and Oral Sorafenib | 2 |
Complete Response Rate
Percentage of participants who achieved a complete response (CR). A CR was defined as normalization of blood counts and a marrow showing less than 5% blasts occurring on or before day 60. (NCT00651261)
Timeframe: Induction therapy (up to 60 days)
| Intervention | percentage of participants (Number) |
|---|
| Induction and Consolidation Chemotherapy Plus Midostaurin | 59 |
| Induction and Consolidation Chemotherapy Plus Placebo | 54 |
Disease-free Survival (DFS)
Disease free survival (DFS) is defined as the time from documentation of first CR at any time to the first of relapse or death from any cause in participants who achieved a CR. (NCT00651261)
Timeframe: Duration of study (Up to 10 years)
| Intervention | months (Median) |
|---|
| Induction and Consolidation Chemotherapy Plus Midostaurin | 26.7 |
| Induction and Consolidation Chemotherapy Plus Placebo | 15.5 |
Event- Free Survival
"Event free survival (EFS) was defined as the time from randomization until the earliest qualifying event, including: failure to obtain a CR on or before 60 days of initiation of protocol therapy; relapse; or death from any cause. Patients alive and event free at the time of analysis were censored on the date of last clinical assessment. The median EFS with 95% CI was estimated using the Kaplan-Meier method.~Due to a higher than expected transplant rate, EFS was promoted to be a key secondary endpoint." (NCT00651261)
Timeframe: Duration of study (Up to 10 years)
| Intervention | months (Median) |
|---|
| Induction and Consolidation Chemotherapy Plus Midostaurin | 8.2 |
| Induction and Consolidation Chemotherapy Plus Placebo | 3.0 |
Overall Survival (OS)
Overall survival (OS) was defined as the time interval from randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. (NCT00651261)
Timeframe: Duration of study (Up to 10 years)
| Intervention | months (Median) |
|---|
| Induction and Consolidation Chemotherapy Plus Midostaurin | 74.7 |
| Induction and Consolidation Chemotherapy Plus Placebo | 25.6 |
Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant
Overall survival (OS) was defined as the time interval from randomization to death from any cause. Any participants who received a stem cell transplant were censored at the time of transplant. The median OS with 95% CI was estimated using the Kaplan-Meier method. (NCT00651261)
Timeframe: Duration of study (Up to 10 years)
| Intervention | months (Median) |
|---|
| Induction and Consolidation Chemotherapy Plus Midostaurin | NA |
| Induction and Consolidation Chemotherapy Plus Placebo | NA |
Overall Response (CR for ALL Patients), (CR + CRp for AML Patients)
"Overall response for ALL patients: CR - complete remission (attainment of an M1 bone marrow (< 5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil count (ANC) > 750/μL and platelet count > 75,000/μL).~Overall response for AML patients: (CR + CRp), defined as:~CR - complete remission (attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral blood counts (absolute neutrophil count (ANC) > 1000/uL and platelet count > 100,000/uL)) or CRp - remission without platelet recovery (Attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of absolute neutrophil count (ANC) > 1000/uL and platelet transfusion independence (defined as: no platelet transfusions x 1 week))." (NCT00372619)
Timeframe: 2 cycles or up to 84 days
| Intervention | participants (Number) |
|---|
| Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients. | 1 |
| Clofarabine 40 mg/m² to Assess Feasibility in AML Patients. | 2 |
| Clofarabine 52 mg/m² to Assess Feasibility in ALL Patients. | 0 |
| Clofarabine 52 mg/m² to Assess Efficacy in ALL Patients. | 2 |
| Clofarabine 52 mg/m² to Assess Feasibility in AML Patients. | 2 |
| Clofarabine 52 mg/m² to Assess Efficacy in AML Patients | 19 |
| Clofarabine 52 mg/m² to Assess Efficacy - Ambiguous Lineage pt | 2 |
Safety and Tolerability as Measured by CTCAE v3.0
Number of participants with at least one grade 3 or higher adverse event during therapy. (NCT00372619)
Timeframe: End of therapy
| Intervention | number participants (Number) |
|---|
| Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients. | 7 |
| Clofarabine 40 mg/m² to Assess Feasibility in AML Patients. | 2 |
| Clofarabine 52 mg/m² to Assess Feasibility in ALL Patients. | 3 |
| Clofarabine 52 mg/m² to Assess Efficacy in ALL Patients. | 10 |
| Clofarabine 52 mg/m² to Assess Feasibility in AML Patients. | 7 |
| Clofarabine 52 mg/m² to Assess Efficacy in AML Patients | 35 |
| Clofarabine 52 mg/m² to Assess Efficacy - Ambiguous Lineage pt | 2 |
Median Event-Free Survival (EFS)
Event-free survival (EFS) defined as time from start of treatment to first documentation of disease relapse or death. Bayesian time-to-event model will be used to monitor progression free survival. (NCT01025154)
Timeframe: 2 years
| Intervention | Months (Median) |
|---|
| Clofarabine, Cytarabine + Idarubicin | 13.5 |
Overall Response: Number of Participants With Complete Remission or Complete Remission Without Platelet Recovery
Overall Response (CR+CRp) defined as Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x 10^9/L and platelet count > 100 x 10^9/L, and normal bone marrow differential (< 5% blasts); and, Complete Remission without Platelet Recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of < 100 x 10^9/L. Response evaluated within 8 weeks after induction therapy. (NCT01025154)
Timeframe: 8 weeks after Induction therapy (induction cycle 4-6 weeks)
| Intervention | participants (Number) |
|---|
| Complete Remission | Complete Remission without Platelet Recovery |
|---|
| Clofarabine, Cytarabine + Idarubicin | 42 | 3 |
Intensive Study: Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact. (NCT03416179)
Timeframe: Baseline up to 25 months
| Intervention | months (Median) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 17.3 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 20.4 |
Intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MD Anderson Symptom Inventory -Acute Myelogenous Leukemia/Myelodysplastic Syndrome (MDASI-AML/MDS) Questionnaire
"MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). Fatigue was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 numeric rating scale (NRS), where 0 = not present and 10 = as bad as you can imagine. Percentage of participants who had improvement in fatigue symptoms reported in this outcome measure." (NCT03416179)
Timeframe: Post-baseline up to Week 8
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 17.41 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 17.24 |
Intensive Study: Percentage of Participants With Complete Remission Including Negative Minimal Residual Disease (CRMRD-neg)
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 49.3 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 47.3 |
Intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC less than (<) 1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutropenia <1.0*10^9/L or platelets <100*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 1.5 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 5.4 |
Intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
Complete remission (CR) was defined based on 2017 European LeukemiaNet (ELN) recommendations. CR: Bone marrow blasts <5 percentage (%); absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) greater than equal to (>=) 1.0*10^9/Liter (L); platelet count >=100*10^9/L. CRMRD-neg: CR with negativity for a genetic marker by reverse transcription quantitative polymerase chain reaction (RT-qPCR), or CR with negativity by Multiparameter Flow Cytometry (MFC). (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 5.0 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 5.4 |
Intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 1.5 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 2.0 |
Intensive Study: Percentage of Participants With Partial Remission (PR)
PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Percentage of participants (Number) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 5.0 |
| Intensive Study: Placebo + Cytarabine + Daunorubicin | 4.4 |
Non-intensive Study: Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact. (NCT03416179)
Timeframe: Baseline up to 25 months
| Intervention | months (Median) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 10.3 |
| Non-intensive Study: Placebo + Azacitidine | 10.6 |
Non-intensive Study: Percentage of Participants Who Improved in Fatigue Score Measured by the MDASI-AML/MDS Questionnaire at Week 12
"MDASI-AML/MDS: consists of 23 items, 13-item core cancer symptoms (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, problem remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness), 4-item AML/MDS specific symptoms (malaise, diarrhea, muscle weakness, and skin problems), and 6 areas of interference (general activity, mood, work, walking, relations with other people, and enjoyment of life). Fatigue was measured at the participants' worst level in last 24 hours by asking participants to respond to each item on an 0-10 NRS, where 0 = not present and 10 = as bad as you can imagine. Percentage of participants who had improvement in fatigue symptoms reported in this outcome measure." (NCT03416179)
Timeframe: Post-baseline up to Week 12
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 11.66 |
| Non-intensive Study: Placebo + Azacitidine | 15.43 |
Non-intensive Study: Percentage of Participants With Complete Remission (CR) Including Negative Minimal Residual Disease (CRMRD-neg)
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 19.6 |
| Non-intensive Study: Placebo + Azacitidine | 13.0 |
Non-intensive Study: Percentage of Participants With Complete Remission With Incomplete Hematologic Recovery (CRi)
CR was defined based on 2017 ELN recommendations. CR: MRD (positive or unknown), bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC <1.0*10^9/L; platelet count <100 × 10^9/L. CRi (included CR [includes CRMRD-neg]): not qualifying for CR, neutrophil <0.5*10^9/L or platelets <50*10^9, absence of extramedullary disease, and absence of blasts with Auer rods. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 2.5 |
| Non-intensive Study: Placebo + Azacitidine | 4.9 |
Non-intensive Study: Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 3.1 |
| Non-intensive Study: Placebo + Azacitidine | 3.1 |
Non-intensive Study: Percentage of Participants With Complete Remission Without Negative Minimal Residual Disease (CRMRD-neg)
CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRMRDneg: CR with negativity for a genetic marker by RT-qPCR, or CR with negativity by MFC. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 1.8 |
| Non-intensive Study: Placebo + Azacitidine | 0.6 |
Non-intensive Study: Percentage of Participants With Morphologic Leukemia-free State (MLFS)
MLFS was defined based on 2017 ELN recommendations. MLFS: MRD (positive or unknown), bone marrow blasts <5%, no hematologic recovery required, marrow should not be aplastic, at least 200 cells enumerated or cellularity absence of extramedullary disease >=10%, and absence of blasts with Auer rods. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 3.1 |
| Non-intensive Study: Placebo + Azacitidine | 0.6 |
Non-intensive Study: Percentage of Participants With Partial Remission (PR)
PR was defined based on 2017 ELN recommendations. PR: MRD (positive or unknown); bone marrow blasts - decrease to 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%; neutrophil count >=1.0*10^9/L; and platelets count >=100*10^9/L. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Percentage of participants (Number) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 2.5 |
| Non-intensive Study: Placebo + Azacitidine | 4.9 |
Intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| AEs | SAEs | Grade 3 or 4 AE | Grade 5 AE |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 196 | 86 | 173 | 16 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 198 | 92 | 169 | 20 |
Intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, creatine phosphokinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Alanine aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Alanine aminotransferase increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Aspartate aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Aspartate aminotransferase increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Blood bilirubin increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Blood bilirubin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Blood bilirubin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Blood bilirubin increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Chronic kidney disease: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Chronic kidney disease: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Chronic kidney disease: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Chronic kidney disease: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Chronic kidney disease: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | CPK increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | CPK increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | CPK increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Creatinine increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Creatinine increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | GGT increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | GGT increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | GGT increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypercalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypercalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyperglycemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyperkalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperkalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyperkalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypermagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypermagnesemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Hypermagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypermagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypermagnesemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypernatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypernatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypernatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypoalbuminemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypoalbuminemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Hypoalbuminemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypoalbuminemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypoalbuminemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypocalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypocalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypocalcemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypoglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypoglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypoglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypokalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypokalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypokalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypomagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypomagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypomagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyponatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyponatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyponatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyponatremia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypophosphatemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Hypophosphatemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade | Hypophosphatemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 1 | 175 | 16 | 1 | 2 | 187 | 2 | 5 | 0 | 173 | 15 | 0 | 184 | 8 | 0 | 4 | 182 | 8 | 1 | 0 | 20 | 161 | 2 | 188 | 7 | 5 | 8 | 0 | 1 | 191 | 1 | 174 | 15 | 2 | 2 | 194 | 2 | 0 | 2 | 0 | 190 | 1 | 0 | 196 | 0 | 0 | 0 | 1 | 185 | 5 | 1 | 1 | 190 | 1 | 1 | 193 | 0 | 155 | 41 | 0 | 2 | 190 | 1 | 177 | 17 | 1 | 1 | 3 | 1 | 153 | 33 | 0 | 3 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 1 | 184 | 13 | 0 | 3 | 192 | 3 | 2 | 1 | 186 | 9 | 3 | 189 | 5 | 1 | 5 | 188 | 4 | 0 | 1 | 19 | 166 | 0 | 192 | 6 | 7 | 11 | 2 | 5 | 192 | 3 | 183 | 10 | 1 | 1 | 194 | 3 | 1 | 4 | 1 | 184 | 2 | 1 | 196 | 1 | 1 | 3 | 1 | 185 | 8 | 1 | 5 | 189 | 3 | 3 | 194 | 1 | 159 | 37 | 2 | 5 | 187 | 0 | 188 | 8 | 1 | 1 | 3 | 1 | 153 | 33 | 2 | 1 |
Intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 0 (CTCAE grade) | Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 1 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Missing (baseline grade) to Grade 0 (CTCAE grade) | INR increased: Missing (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Missing (baseline grade) to Grade 2 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 0 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 2 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 3 (CTCAE grade) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 0 | 1 | 4 | 2 | 1 | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 1 | 1 | 1 | 3 | 1 | 0 |
Intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| QTcB: <=450 msec (baseline) to <=450 msec (post-baseline) | QTcB: <=450 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: <=450 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: <=450 msec (baseline) to >500 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to <=450 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >500 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >500 msec (post-baseline) | QTcB: >500 msec (baseline) to >500 msec (post-baseline) | QTcF: <=450 msec (baseline) to <=450 msec (post-baseline) | QTcF: <=450 msec (baseline) to >450-<=480 msec (post-baseline) | QTcF: <=450 msec (baseline) to >480-<=500 msec (post-baseline) | QTcF: <=450 msec (baseline) to >500 msec (post-baseline) | QTcF: >450-<=480 msec (baseline) to <=450 msec (post-baseline) | QTcF: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) | QTcF: >450-<=480 msec (baseline) to >500 msec (post-baseline) | QTcF: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 51 | 64 | 18 | 11 | 2 | 20 | 16 | 1 | 1 | 2 | 1 | 1 | 116 | 50 | 8 | 5 | 2 | 5 | 1 | 0 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 71 | 63 | 11 | 6 | 3 | 17 | 10 | 5 | 0 | 1 | 0 | 1 | 132 | 39 | 10 | 0 | 1 | 5 | 1 | 1 |
Intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hematology laboratory test included: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Anemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Anemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Anemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Anemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Anemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hemoglobin increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hemoglobin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hemoglobin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | INR increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Neutrophil count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Platelet count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Platelet count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Platelet count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | White blood cell decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 0 | 27 | 113 | 4 | 52 | 0 | 194 | 2 | 3 | 0 | 0 | 21 | 160 | 1 | 11 | 0 | 185 | 6 | 1 | 1 | 0 | 4 | 85 | 0 | 105 | 1 | 98 | 97 | 1 | 3 | 155 | 37 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 2 | 14 | 103 | 5 | 73 | 2 | 194 | 1 | 1 | 2 | 4 | 26 | 152 | 0 | 9 | 6 | 180 | 4 | 3 | 0 | 4 | 2 | 79 | 2 | 106 | 2 | 100 | 95 | 4 | 2 | 156 | 35 |
Intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event. (NCT03416179)
Timeframe: Day 1 up to maximum of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment related AEs | Treatment related SAEs | Grade 3 or 4 AE | Grade 5 AE |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 181 | 48 | 161 | 5 |
,| Intensive Study: Placebo + Cytarabine + Daunorubicin | 188 | 60 | 149 | 8 |
Intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Ctrough of Glasdegib was measured in nanogram per milliliter (ng/mL). (NCT03416179)
Timeframe: Induction, Day 10+/-1: pre-dose, 1, 4 hour (hr); Consolidation phase, Day 1: pre-dose, 1, 4 hr
| Intervention | ng/ml (Geometric Mean) |
|---|
| Induction Day 10 | Consolidation 1, Day 1 | Consolidation 2, Day 1 |
|---|
| Intensive Study: Glasdegib + Cytarabine + Daunorubicin | 413.54 | 245.48 | 259.79 |
Non-intensive Study: Number of Participants With Adverse Events (AEs),Serious Adverse Events (SAEs) and According to Severity AEs Graded by NCI CTCAE v.4.03
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. AEs included SAEs and all non-SAEs. NCI CTCAE v.4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| AEs | SAEs | Grade 3 or 4 AE | Grade 5 AE |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 161 | 117 | 106 | 50 |
,| Non-intensive Study: Placebo + Azacitidine | 158 | 124 | 100 | 52 |
Non-intensive Study: Number of Participants With Shift From Baseline in Chemistry Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Chemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, chronic kidney disease, CPK increased, creatinine increased, GGT increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for chemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Alanine aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Alanine aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Alanine aminotransferase increased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Alkaline phosphatase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Aspartate aminotransferase increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Aspartate aminotransferase increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Blood bilirubin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Blood bilirubin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Chronic kidney disease: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Chronic kidney disease: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Chronic kidney disease: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Chronic kidney disease: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | CPK increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | CPK increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | CPK increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Creatinine increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Creatinine increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | GGT increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | GGT increased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | GGT increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypercalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypercalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyperglycemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperkalemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hyperkalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperkalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyperkalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyperkalemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypermagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypermagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypermagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypernatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypernatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypoalbuminemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypoalbuminemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypoalbuminemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypocalcemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypocalcemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypocalcemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypocalcemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypoglycemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypoglycemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypoglycemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypokalemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypokalemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypokalemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypokalemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypokalemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypomagnesemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypomagnesemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypomagnesemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypomagnesemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyponatremia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hyponatremia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Hyponatremia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hyponatremia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hypophosphatemia: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Hypophosphatemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade | Hypophosphatemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Hypophosphatemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 2 | 152 | 6 | 0 | 0 | 159 | 0 | 3 | 152 | 4 | 157 | 3 | 2 | 130 | 28 | 0 | 9 | 147 | 1 | 153 | 7 | 3 | 4 | 1 | 2 | 156 | 2 | 147 | 8 | 2 | 2 | 155 | 2 | 0 | 0 | 2 | 155 | 2 | 158 | 2 | 2 | 151 | 6 | 2 | 154 | 1 | 0 | 2 | 155 | 3 | 2 | 129 | 23 | 1 | 4 | 2 | 151 | 6 | 0 | 135 | 24 | 0 | 1 | 3 | 1 | 141 | 12 | 0 | 1 |
,| Non-intensive Study: Placebo + Azacitidine | 0 | 154 | 6 | 0 | 1 | 157 | 1 | 0 | 156 | 4 | 159 | 1 | 1 | 134 | 23 | 2 | 8 | 147 | 2 | 155 | 5 | 5 | 3 | 0 | 2 | 158 | 4 | 136 | 14 | 2 | 0 | 157 | 3 | 0 | 0 | 4 | 154 | 2 | 159 | 1 | 0 | 157 | 3 | 2 | 155 | 3 | 0 | 4 | 156 | 0 | 0 | 139 | 15 | 2 | 4 | 4 | 153 | 2 | 1 | 142 | 15 | 1 | 2 | 2 | 0 | 138 | 17 | 1 | 2 |
Non-intensive Study: Number of Participants With Shift From Baseline in Coagulation Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Coagulation laboratory test included: activated partial thromboplastin time prolonged, and INR increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 0= no abnormality; Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for coagulation were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Activated partial thromboplastin time prolonged: Missing (baseline grade) to Grade 0 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 0 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) | Activated partial thromboplastin time prolonged: Grade 2 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Missing (baseline grade) to Grade 0 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 0 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 2 (CTCAE grade) | INR increased: Grade 0 (baseline grade) to Grade 3 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 1 (CTCAE grade) | INR increased: Grade 1 (baseline grade) to Grade 2 (CTCAE grade) | INR increased: Grade 3 (baseline grade) to Grade 1 (CTCAE grade) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 1 | 8 | 5 | 1 | 1 | 1 | 1 | 4 | 6 | 1 | 1 | 1 | 2 | 1 |
,| Non-intensive Study: Placebo + Azacitidine | 0 | 5 | 7 | 0 | 0 | 0 | 0 | 5 | 4 | 2 | 0 | 1 | 0 | 1 |
Non-intensive Study: Number of Participants With Shift From Baseline in Corrected QT (QTc) Interval
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of <=450 to >500 msec (post-baseline) were summarized. Number of participants with shift from baseline for QTc were assessed. Only those QTc parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| QTcB: <=450 msec (baseline) to <=450 msec (post-baseline) | QTcB: <=450 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: <=450 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: <=450 msec (baseline) to >500 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to <=450 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: >450-<=480 msec (baseline) to >500 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >450-<=480 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >480-<=500 msec (post-baseline) | QTcB: >480-<=500 msec (baseline) to >500 msec (post-baseline) | QTcF: <=450 msec (baseline) to <=450 msec (post-baseline) | QTcF: <=450 msec (baseline) to >450-<=480 msec (post-baseline) | QTcF: <=450 msec (baseline) to >480-<=500 msec (post-baseline) | QTcF: >450 - <=480 (baseline) to <=450msec (post-baseline) | QTcF: >450 - <=480 msec (baseline) to >450 - <=480msec(post baseline) | QTcF: >450 - <=480 msec (baseline) to >480 - <=500 msec (post baseline) | QTcF: >480 msec (baseline) to <=500 msec (post baseline) | QTcF: >450 - <=480 (baseline) to >500 msec (post baseline) | QTcF: >480 - <=500msec (baseline) to >480 - <=500 msec (post baseline) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 48 | 53 | 6 | 7 | 0 | 20 | 13 | 5 | 1 | 3 | 2 | 100 | 39 | 7 | 1 | 0 | 5 | 1 | 1 | 1 |
,| Non-intensive Study: Placebo + Azacitidine | 58 | 43 | 11 | 3 | 1 | 22 | 8 | 3 | 2 | 1 | 3 | 104 | 36 | 0 | 1 | 1 | 8 | 4 | 1 | 0 |
Non-intensive Study: Number of Participants With Shift From Baseline in Hematological Laboratory Abnormalities Graded by NCI CTCAE v.4.03
Hematology laboratory test included: anemia, hemoglobin increased, INR increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Number of participants with shift from baseline for hematology laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Anemia: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Anemia: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Anemia: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Anemia: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Hemoglobin increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Hemoglobin increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count increased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count increased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Lymphocyte count increased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Lymphocyte count increased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Neutrophil count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Neutrophil count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | Platelet count decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | Platelet count decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | Platelet count decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | Platelet count decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Missing (baseline grade) to Grade <=2 (CTCAE grade) | White blood cell decreased: Missing (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Grade <=2 (baseline grade) to Grade <=2 (CTCAE grade) | White blood cell decreased: Grade <=2 (baseline grade) to Grade 3/4 (CTCAE grade) | White blood cell decreased: Grade 3/4 (baseline grade) to Grade <=2 (CTCAE grade) | White blood cell decreased: Grade 3/4 (baseline grade) to Grade 3/4 (CTCAE grade) |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 29 | 97 | 5 | 29 | 160 | 0 | 2 | 1 | 96 | 51 | 2 | 7 | 3 | 147 | 7 | 2 | 4 | 13 | 48 | 2 | 92 | 21 | 55 | 1 | 83 | 1 | 1 | 43 | 70 | 0 | 45 |
,| Non-intensive Study: Placebo + Azacitidine | 41 | 87 | 1 | 31 | 159 | 1 | 0 | 0 | 89 | 54 | 4 | 13 | 0 | 157 | 3 | 0 | 0 | 22 | 40 | 1 | 97 | 28 | 64 | 0 | 68 | 0 | 0 | 48 | 62 | 1 | 48 |
Non-intensive Study: Number of Participants With Treatment Related Adverse Events (AEs) and Serious Adverse Events (SAEs) Graded by NCI CTCAE v.4.03
A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. SAE: any AE, regardless of dose, that led to death; was life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant incapacity or led to congenital anomaly or birth defect. NCI CTCAE v4.03, Grade 3=severe adverse event, Grade 4= life threatening consequences; urgent intervention indicated, Grade 5= death related to adverse event. (NCT03416179)
Timeframe: Day 1 up to maximum of 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment related AEs | Treatment related SAEs | Grade 3 or 4 AE | Grade 5 AE |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 133 | 45 | 97 | 4 |
,| Non-intensive Study: Placebo + Azacitidine | 123 | 37 | 72 | 4 |
Non-intensive Study: Plasma Trough Concentration (Ctrough) of Glasdegib
Ctrough of Glasdegib was measured in ng/mL. (NCT03416179)
Timeframe: Pre-dose: Cycle 1 Day 15 and Cycle 2 Day 1
| Intervention | ng/ml (Geometric Mean) |
|---|
| Cycle 1 Day 15 | Cycle 2 Day 1 |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 565.44 | 472.42 |
Non-intensive Study: Time to Response
TTRi:Participants who achieved CRi or better, as the time from date of randomization to first documentation of response(CRi or better).TTRh:Participants who achieved CRh or better, as the time from date of randomization to first documentation of response(CRh or better). CRi:not qualifying for CR, neutrophil<0.5*10^9/L or platelets<50*10^9, absence of extramedullary disease,absence of blasts with Auer rods. CR was defined based on 2017 ELN recommendations. CR: Bone marrow blasts <5 %; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC >=1.0*10^9/L; platelet count >=100*10^9/L. CRh: MRD (positive or unknown); bone marrow blasts <5%; assessed in non-intensive chemotherapy study only, not qualifying for CR, ie, both neutrophil >=0.5*10^9/L and platelets >=50*10^9/L must be met, but does not satisfy both neutrophils >=1*10^9/L and platelets >=100*10^9/L at the same time; absence of extramedullary disease; and absence of blasts with Auer rods. (NCT03416179)
Timeframe: From the date of randomization to the first documentation of response (CRi/CRh or better) (maximum up to 3 years)
| Intervention | Months (Mean) |
|---|
| TTRi | TTRh |
|---|
| Non-intensive Study: Glasdegib + Azacitidine | 4.057 | 4.334 |
,| Non-intensive Study: Placebo + Azacitidine | 4.093 | 4.146 |
Overall Survival
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. (NCT01399372)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.3 years.
| Intervention | years (Median) |
|---|
| Chemotherapy | NA |
| Chemotherapy + Low-Dose WBRT | NA |
Percentage of Participants Experiencing Partial Response or Complete Response
Response was evaluated using the international criteria proposed by the International Primary Central Nervous System Lymphoma (PCNSL) Study Group criteria. Complete Response was defined as no contrast brain enhancement on magnetic resonance imaging (MRI), no corticosteroid use for at least 2 weeks, a normal eye exam, and negative CSF cytology. Partial response was defined as at least 50% decrease in enhancing tumor on MRI compared with baseline imaging, no or minor retinal pigment epithelium (RPE) abnormality, and negative CSF cytology. (NCT01399372)
Timeframe: After 4th cycle of chemotherapy, approximately 4 months after randomization.
| Intervention | percentage of participants (Number) |
|---|
| Chemotherapy | 83.3 |
| Chemotherapy + Low-Dose WBRT | 80.6 |
Percentage of Participants With Neurocognitive Failure
Neurocognitive failure is defined as cognitive failure on two or more of the following tests: Hopkins Verbal Learning Test - Revised (HVLT-R) Free Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test Part A, Trail Making Test Part B, and Controlled Oral Word Association. Cognitive failure for each test is defined as a change from baseline in raw score (post baseline score - baseline score) at or exceeding the minimally important difference reported in the literature [determined by the reliable change index (RCI) method] of -5, -3, -2,12, 26, and -12, respectively, indicating a worsening of neurocognitive function. Time to neurocognitive failure is defined as time from randomization to date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method and the distributions of failure times are compared between the arms. Two-year estimates are provided here. (NCT01399372)
Timeframe: Neurocognitive function tests were administered at baseline, after cycle 4 of treatment (4 months), then every six months after end of treatment (7 months) for five years. Two-year rates are provided here.
| Intervention | percentage of participants (Number) |
|---|
| Chemotherapy | 31.6 |
| Chemotherapy + Low-Dose WBRT | 17.9 |
Progression-free Survival
Progression is defined as any of the following: more than 25% increase in the contrast-enhancing lesion seen on magnetic resonance imaging (MRI) compared with baseline or best response; new site of disease (central nervous system or systemic); recurrent or new ocular disease; recurrent or positive cerebrospinal fluid (CSF) cytology. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (NCT01399372)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.3 years.
| Intervention | years (Median) |
|---|
| Chemotherapy | 2.1 |
| Chemotherapy + Low-Dose WBRT | NA |
Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
"Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 very poor to 7 excellent such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Data through five years after end of protocol treatment is included in the analysis, while summary data is provided only through three years due to very few participants after that timepoint." (NCT01399372)
Timeframe: EORTC QLQ-C30 was administered at baseline, after cycle 4 of treatment (4 months), then every six months after end of treatment (7 months) for five years.
| Intervention | score on a scale (Mean) |
|---|
| Baseline | End of cycle 4 | 6 Months Post-Treatment | 12 Months Post-Treatment | 18 Months Post-Treatment | 24 Months Post-Treatment | 30 Months Post-Treatment | 36 Months Post-Treatment | 42 Months Post-Treatment | 48 Months Post-Treatment | 54 Months Post-Treatment | 60 Months Post-Treatment |
|---|
| Chemotherapy | 62.78 | 67.67 | 74.54 | 78.47 | 76.79 | 70.83 | 77.08 | 75.00 | 75.00 | 79.76 | 70.24 | 80.56 |
,| Chemotherapy + Low-Dose WBRT | 54.90 | 64.58 | 75.35 | 78.99 | 76.67 | 83.33 | 79.63 | 85.00 | 77.56 | 84.38 | 91.67 | 83.33 |
Number of Participants With a Response
Response - Complete remission (CR): Normalization peripheral blood & bone marrow 5% or & platelet count >100x10^9/L; CR with incomplete platelet recovery (CRp): CR but platelet count <100x10^9/L. CR with incomplete recovery (CRi): CR but platelet count <100x10^9/L or absolute neutrophil count < 1x10^9/L. Partial response (PR): As above except for presence of 6-25% marrow blasts. Lymphoblastic lymphoma (& ALL subtypes with extramedullary disease): CR - disappearance all known disease. PR - >50% decrease in tumor size using sum of product, includes 50% volume decrease in lesions measurable in 3 dimensions. No Response (NR) - No significant change (includes stable disease). Lesions decreased size but <50% or lesions with slight enlargement <25% increase in size. Progressive Disease (PD): Appearance new lesions, 25% or > increase in size existing lesions (>50% if 1 lesion & <2). (NCT00671658)
Timeframe: Response assessed following first 21 day course up to end of treatment with 8 cycles, up to 210 days
| Intervention | Participants (Number) |
|---|
| Complete Response (CR) | Complete Response without Platelet Recovery | Partial Response (PR) |
|---|
| HYPER-CVAD | 198 | 3 | 4 |
Immunogenicity
Number of Patients with Positive Immunogenicity tests (NCT00671034)
Timeframe: 25 Days Post-dose (Day 29)
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Calaspargase Pegol 2100) | 2 |
| Arm II (Calaspargase Pegol 2500) | 2 |
| Arm III (Pegaspargase 2500) | 4 |
Percentage of Participants With Complete Remission at the End of Induction
Complete Remission (CR) rate; where CR is defined as M1 marrow (< 5% lymphoblasts in the bone marrow) (NCT00671034)
Timeframe: End of induction (Day 29)
| Intervention | Percentage of participants (Number) |
|---|
| Arm I (Calaspargase Pegol 2100) | 92.4 |
| Arm II (Calaspargase Pegol 2500) | 97.6 |
| Arm III (Pegaspargase 2500) | 94.1 |
Percentage of Participants With Event-free Survival (EFS)
Percentage of participants who were event free. Event Free Probability defined as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignant neoplasm, remission death) or date of last contact for subjects who are event-free. (NCT00671034)
Timeframe: 5 Years
| Intervention | Percentage of participants (Number) |
|---|
| Arm I (Calaspargase Pegol 2100) | 72.35 |
| Arm II (Calaspargase Pegol 2500) | 80.8 |
| Arm III (Pegaspargase 2500) | 79.34 |
Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction
Percentage of participants with Negative MRD (MRD<0.01%). (NCT00671034)
Timeframe: End of induction (Day 29)
| Intervention | Percentage of participants (Number) |
|---|
| Arm I (Calaspargase Pegol 2100) | 65.2 |
| Arm II (Calaspargase Pegol 2500) | 81 |
| Arm III (Pegaspargase 2500) | 72.5 |
Asparaginase Level
The proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on Days 4, 15, 22 and 29 of Induction compared to Oncaspar (NCT00671034)
Timeframe: Days 4, 15, 22 and 29 of Induction
| Intervention | percentage of patients (Number) |
|---|
| Level at least 0.1 IU/mL day 4 | Level at least 0.1 IU/mL day 15 | Level at least 0.1 IU/mL day 22 | Level at least 0.1 IU/mL day 29 | Level at least 0.4 IU/mL day 4 | Level at least 0.4 IU/mL day 15 | Level at least 0.4 IU/mL day 22 | Level at least 0.4 IU/mL day 29 |
|---|
| Arm I (Calaspargase Pegol 2100) | 0 | 98.4 | 98.2 | 94.9 | 0 | 75.8 | 37.5 | 13.6 |
,| Arm II (Calaspargase Pegol 2500) | 0 | 100 | 100 | 95.0 | 0 | 95.0 | 62.5 | 27.5 |
,| Arm III (Pegaspargase 2500) | 0 | 100 | 95.1 | 28.6 | 0 | 93.0 | 14.6 | 0 |
Pharmacodynamics (PD)
Plasma Asparaginase Concentration During consolidation and induction. (NCT00671034)
Timeframe: Day 29 of consolidation and induction
| Intervention | mIU/mL (Median) |
|---|
| Plasma Asparaginase Concentration- Consolidation | Plasma Asparaginase Concentration- Induction |
|---|
| Arm I (Calaspargase Pegol 2100) | 575.9 | 271.6 |
,| Arm II (Calaspargase Pegol 2500) | 617.2 | 339.6 |
,| Arm III (Pegaspargase 2500) | 562.1 | 72.8 |
Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy)
Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half. (NCT00671034)
Timeframe: Post Day 29 of Induction and Post Day 22 of Consolidation
| Intervention | hours (Mean) |
|---|
| Asparaginase half-life during Consolidation | Asparaginase half-life during Induction |
|---|
| Arm I (Calaspargase Pegol 2100) | 415.8 | 305.1 |
,| Arm II ( Calaspargase Pegol 2500) | 355.9 | 321.5 |
,| Arm III (Pegaspargase 2500) | 117.2 | 126.9 |
Plasma and CSF Concentrations of Asparagine in ug/ml
The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar. (NCT00671034)
Timeframe: 25 Days Post-dose (Day 29)
| Intervention | ug/mL (Mean) |
|---|
| CSF asparagine concentration (ug/mL) | Plasma asparagine concentration (ug/mL) |
|---|
| Arm I (Calaspargase Pegol 2100) | 0.2 | 0.2 |
,| Arm II (Calaspargase Pegol 2500) | 0.19 | 0.25 |
,| Arm III (Pegaspargase 2500) | 0.26 | 0.83 |
Toxicities During Post Induction Intensification Therapy (All Grades)
The calculation of AE incidence will be based on the number of patients per AE category. For each patient who has multiple AEs classified to the same category, that patient will be tabulated under the worst toxicity grade for that AE category. The incidence of AEs will be tabulated by treatment arm and by organ class. Special attention will be paid to hypersensitivity, pancreatitis, coagulopathy, infection, neurologic dysfunction and thromboembolic events. (NCT00671034)
Timeframe: Up to 5 years
| Intervention | Percentage of participants (Number) |
|---|
| Alergic Reaction - Consolidation | Alergic Reaction - Delayed Intensification I | Alergic Reaction - Interim Maintenance I | CNS - Consolidation | CNS - Delayed Intensification I | CNS - Interim Maintenance I | Hyperbilirubinemia - Consolidation | Hyperbilirubinemia - Delayed Intensification I | Hyperbilirubinemia - Interim Maintenance I | Hyperglycemia - Consolidation | Hyperglycemia - Delayed Intensification I | Hyperglycemia - Interim Maintenance I | Hyperlipidemia - Consolidation | Hyperlipidemia - Delayed Intensification I | Hyperlipidemia - Interim Maintenance I | % patients w/INR increase - Consolidation | % pts w/INR increase - Delayed Intensification I | % patients w/INR increase - Interim Maintenance I | Pancreatitis - Consolidation | Pancreatitis -Delayed Intensification I | Pancreatitis - Interim Maintenance I | % pts w/prolongation of APT time - Consolidation | % pts w/prolongation APT time -Delayed Intension I | %pts w/prolongation APT time-Interim maintenance I | Thrombosis - Consolidation | Thrombosis - Delayed Intensification I | Thrombosis - Interim Maintenance I |
|---|
| Arm I (Calaspargase Pegol 2100) | 20.4 | 4.4 | 0.0 | 0.0 | 0.0 | 0.0 | 53.1 | 28.9 | 41.3 | 44.9 | 44.4 | 34.8 | 2.0 | 2.2 | 2.2 | 6.1 | 6.7 | 2.2 | 10.2 | 2.2 | 2.2 | 8.2 | 8.9 | 6.5 | 0.0 | 2.2 | 0.0 |
,| Arm II (Calaspargase Pegol 2500) | 27.3 | 0.0 | 0.0 | 0.0 | 3.8 | 0.0 | 45.5 | 38.5 | 27.6 | 42.4 | 61.5 | 44.8 | 3.0 | 0.0 | 3.4 | 3.0 | 3.8 | 0.0 | 6.1 | 7.7 | 3.4 | 9.1 | 26.9 | 6.9 | 0.0 | 0.0 | 0.0 |
,| Arm III (Pegaspargase 2500) | 23.3 | 0.0 | 2.1 | 0.0 | 2.6 | 0.0 | 30.2 | 10.5 | 33.3 | 46.5 | 36.8 | 33.3 | 7.0 | 0.0 | 2.6 | 7.0 | 0.0 | 2.6 | 7.0 | 0.0 | 2.6 | 7.0 | 18.4 | 7.7 | 2.3 | 0.0 | 0.0 |
Dose Limiting Toxicity
Number of participants with dose limiting toxicity. (NCT00666588)
Timeframe: During Course 1
| Intervention | participants (Number) |
|---|
| Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure | 0 |
| Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp | 1 |
| Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp | 0 |
| Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp | 0 |
Overall Response (Complete Remission [CR] and CR With Partial Recovery [CRp]) During Course 1
Overall response (complete remission [CR] and CR with partial recovery [CRp]) during course 1. (NCT00666588)
Timeframe: After course 1
| Intervention | participants (Number) |
|---|
| Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure | 4 |
| Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp | 2 |
| Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp | 2 |
| Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp | 9 |
Feasibility of Stem Cell Quantitation: Percentage of Leukemia Initiation Cells (LIC) Depletion
Descriptive statistics to assess mean +/- standard deviation for the percentage leukemia initiation cells (LIC) depletion. (NCT00666588)
Timeframe: At baseline and after completion of course 1
| Intervention | percentage of LIC depletion (Mean) |
|---|
| Prior to Treatment | Post Treatment |
|---|
| Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp | 1.6385 | 0.0435 |
,| Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp | 0.2 | 0.43 |
,| Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure | 0.013667 | 0.021 |
NF-kB Activity by Enzyme-linked Immunosorbent Assay (ELISA)
NF-kB activity will be measured as a continuous variable (ng NF-kB/Mg protein). Differences in NF-κB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range. We may perform exploratory analyses to determine if single time point measurements, or the difference between time points, correlate with treatment response. (NCT00666588)
Timeframe: At baseline, prior to and up to 24 hours after bortezomib treatment
| Intervention | ng/Mg protein (Mean) |
|---|
| Baseline | 24 Hrs after treatment |
|---|
| Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp | 655.4 | 345.46 |
,| Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp | 408.144 | 497.31 |
,| Bortezomib 1.3 mg/m2-assess Feasibility High Anthracycline Exp | 974.66 | 855.96 |
,| Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure | 718.218 | 774.1925 |
Proteasome Inhibition Activity
Mean and standard deviation of β1 and β5- Results are ratios (proteasome subunit/β-actin based on loading of 15 µg total protein, normalized to CEM). (NCT00666588)
Timeframe: At baseline
| Intervention | ratio (Mean) |
|---|
| Baseline β1 | Baseline β5 |
|---|
| Bortezomib 1.0mg/m2-assess Feasibility High Anthracycline Exp | 0.7894 | 0.2576 |
,| Bortezomib 1.3 mg/m2-assess Efficacy High Anthracycline Exp | 0.2895143 | 0.3721286 |
,| Bortezomib 1.3mg/m2-assess Efficacy-low Anthracycline Exposure | 0.08115 | 0.121575 |
Complete Remission (CR) Rate for First 60 Participants
All responses were defined as per IWG criteria (2003) where CR Rate defined as number of participants with CR out of total treated participants. Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/L, and normal bone marrow differential (< 5% blasts). Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy. (NCT00778375)
Timeframe: Evaluation following two 10 day cycles on day 21 of therapy, continuing up to 210 days
| Intervention | Percentage of Participants (Number) |
|---|
| Clofarabine + Cytarabine + Decitabine | 58 |
Disease-free (DFS) or Relapse-free Survival (RFS) Time
Disease (DFS) or Relapse-free survival (RFS): Time from date of treatment start until the date of first objective documentation of disease-relapse; Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy and then every 2 weeks (+/- 7 days) as required by leukemia evolution until remission or non-response. Among participants who achieved CR or CRp, RFS was defined as the time interval between the date of response (ie CR or CRp) and the date of relapse or date of death, whichever occurs first. CR or CRp participants who were alive and relapse-free were censored at the off-study date. Full range reflects time to disease progression only, therefore does not reflect a lesser survival time due to other reasons than disease progression/relapse. (NCT00778375)
Timeframe: Evaluated from treatment date until date of disease progression/relapse, followed for 5 years/60 months.
| Intervention | Months (Median) |
|---|
| Clofarabine + Cytarabine + Decitabine | 15.9 |
Event Free Survival (EFS)
EFS is defined as length of time after primary treatment for a cancer ends that the participant remains free of certain complications or events that the treatment was intended to prevent or delay, for example but not exclusive of hematologic and non-hematologic toxicities, cumulative toxicities with consolidation courses, or emergence of resistance to the chemotherapy component of treatment. (NCT00778375)
Timeframe: Follow up up to 5 years/60 months.
| Intervention | Months (Median) |
|---|
| Clofarabine + Cytarabine + Decitabine | 7.7 |
Overall Response Rate (CR, CRp/CRi and PR)
IWG Response criteria (2003): Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/L, and normal bone marrow differential (< 5% blasts). Complete Remission without Platelet Recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of < 100 x 10^9/L or Complete remission with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts; Partial Remission (PR): Blood count recovery as for CR, but with both a decrease in marrow blasts of at least 50% and not more than 6 to 25% abnormal cells in the marrow. Participants not achieving a complete remission following first induction course, can receive a second induction course at least 28 days following first to optimize response if possible. (NCT00778375)
Timeframe: Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days
| Intervention | Percentage of Participants (Number) |
|---|
| Clofarabine + Cytarabine + Decitabine | 73 |
Median Overall Survival (OS)
Overall survival (OS): Time from date of treatment start until date of death due to any cause. (NCT00778375)
Timeframe: Evaluated from treatment date until date of death, followed for 5 years/60 months.
| Intervention | Months (Median) |
|---|
| Overall Survival | Overall Survival among Responders ((n=86) |
|---|
| Clofarabine + Cytarabine + Decitabine | 11.1 | 21.1 |
Number of Participants With Complete Remission [Complete Response (CR), Complete Response With Platelet Recover (CRp) or Complete Response With Incomplete Marrow Recovery (CRi)]
All responses were defined as per IWG criteria (2003) where CR Rate defined as number of participants with CR out of total treated participants. Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 times 10^9/L and platelet count > 100 times 10^9/L, and normal bone marrow differential (< 5% blasts). Complete response with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts. Bone marrow aspirate and/or biopsy starting on day 21 (+/- 7 days) of therapy. (NCT00778375)
Timeframe: Beginning assessment following two 10-day induction cycles through an additional re-induction cycle, up to 40 days
| Intervention | Participants (Number) |
|---|
| CR | CRp/CRi |
|---|
| Induction Clofarabine + Cytarabine + Decitabine | 60 | 9 |
,| Re-Induction | 12 | 4 |
Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)
Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria was defined as: less than 5 percent (%) blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets greater than (>)100*10^9 cells/liter (L) and absolute neutrophil count (ANC) >1.0*10^9 cells/L. This outcome measure was planned to be analyzed for specified arm only. (NCT03384654)
Timeframe: Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 0 |
Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL
Complete response based on the modified NCCN criteria was defined as: less than 5% blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets >100*10^9 cells/L and ANC >1.0*10^9 cells/L. This outcome measure was planned to be analyzed for specified arms only. (NCT03384654)
Timeframe: End of Cycle 1 (that is, up to 28 days)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 2: T-Cell ALL (1-17 Years) | 41.7 |
| Cohort 2: T-Cell ALL (18-30 Years) | 60.0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 30.0 |
Event-free Survival (EFS)
EFS was defined as the time (in months) from the date of first treatment to the first documented treatment failure (that is [ie], disease progression) or date of relapse from CR or death due to any cause, whichever occurred first. Per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow; reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in the absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for the analysis. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Months (Median) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 1.1 |
| Cohort 2: T-Cell ALL (1-17 Years) | 8.9 |
| Cohort 2: T-Cell ALL (18-30 Years) | 10.3 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 2.9 |
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum observed serum concentration of daratumumab. (NCT03384654)
Timeframe: Cohort 1: B-cell ALL: End of infusion (EOI) on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): EOI on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): EOI on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): EOI on Day 22 of Cycle 2
| Intervention | Micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 494 |
| Cohort 2: T-Cell ALL (1-17 Years) | 763 |
| Cohort 2: T-Cell ALL (18-30 Years) | 501 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 758 |
Minimal Residual Disease (MRD) Negative Rate
MRD negative rate was defined as the percentage of participants who were considered MRD negative after MRD testing by bone marrow aspirate at any timepoint after first study treatment administration and before disease progression or starting subsequent anti-cancer therapy or allogeneic hematopoietic stem cell transplant (HSCT). MRD negative was defined as less than (<) 0.01% abnormal population counts to nucleated mononuclear cells when measured by flow cytometry. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 0 |
| Cohort 2: T-Cell ALL (1-17 Years) | 45.8 |
| Cohort 2: T-Cell ALL (18-30 Years) | 20.0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 50.0 |
Minimum Observed Serum Concentration (Cmin) of Daratumumab
Cmin was defined as minimum observed serum concentration of daratumumab. (NCT03384654)
Timeframe: Cohort 1: B-cell ALL: Predose on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): Predose on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): Predose on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): Predose on Day 22 of Cycle 2
| Intervention | mcg/mL (Mean) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 172 |
| Cohort 2: T-Cell ALL (1-17 Years) | 369 |
| Cohort 2: T-Cell ALL (18-30 Years) | 172 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 365 |
Number of Participants With Anti-daratumumab Antibodies
Number of participants with anti-daratumumab antibodies was reported. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 0 |
| Cohort 2: T-Cell ALL (1-17 Years) | 0 |
| Cohort 2: T-Cell ALL (18-30 Years) | 0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 0 |
Overall Response Rate (ORR)
For ALL participants, ORR was defined as percentage of participants who achieved CR or CR with only partial hematological recovery(CRi) as per NCCN criteria. CR for ALL: less than 5% blasts in bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets >100*10^9 cells/L and ANC >1.0*10^9 cells/L. CRi for ALL: less than 5% blasts in bone marrow; no evidence of circulating blasts or extramedullary disease; partial recovery of peripheral blood counts not meeting criteria for CR. For LL participants, ORR was defined as percentage of participants who had CR or PR during or after treatment administration but prior to start of subsequent anti-cancer therapy or allogeneic hematopoietic stem cell transplant(HSCT). CR for LL: disappearance of all evidence of disease from all sites. PR for LL: decrease of >=50% in sum of products of diameter of lesions of up to 6 of largest dominant nodes or nodal masses with no new lesions. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 14.3 |
| Cohort 2: T-Cell ALL (1-17 Years) | 83.3 |
| Cohort 2: T-Cell ALL (18-30 Years) | 80.0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 50.0 |
Overall Survival (OS)
OS was defined as the time (in months) from the date of first study drug administration to the date of death due to any cause. Kaplan-Meier method was used for the analysis. Participants who died after consent withdrawal were considered as having an OS event. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Months (Median) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 3.2 |
| Cohort 2: T-Cell ALL (1-17 Years) | 10.9 |
| Cohort 2: T-Cell ALL (18-30 Years) | 12.0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 4.2 |
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Percentage of participants who received an allogeneic HSCT after treatment with daratumumab were reported. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Percentage of participants (Number) |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | 14.3 |
| Cohort 2: T-Cell ALL (1-17 Years) | 75.0 |
| Cohort 2: T-Cell ALL (18-30 Years) | 60.0 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | 30.0 |
Relapse-free Survival (RFS)
RFS was defined as the time (in months) from CR to relapse from CR, or disease progression or death due to any cause, whichever occurred first. For ALL, as per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow, or reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for analysis. (NCT03384654)
Timeframe: Up to 4 years 4 months
| Intervention | Months (Median) |
|---|
| Cohort 2: T-Cell ALL (1-17 Years) | 19.4 |
| Cohort 2: T-Cell ALL (18-30 Years) | 9.4 |
| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | NA |
Concentration of Daratumumab in Cerebrospinal Fluid (CSF)
Concentration of daratumumab in CSF was reported. '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points. (NCT03384654)
Timeframe: Pre-dose on Cohort 1: Cycles 1 and 2: Day 1; Cohort 2: Cycle 1 Day 1 and Day 15 and Cycle 2 Day 2 and Day 15
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 Day 1 predose | Cycle 2 Day 1 predose |
|---|
| Cohort 1: B-cell ALL (1-17 Years) | NA | 0.573 |
Concentration of Daratumumab in Cerebrospinal Fluid (CSF)
Concentration of daratumumab in CSF was reported. '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points. (NCT03384654)
Timeframe: Pre-dose on Cohort 1: Cycles 1 and 2: Day 1; Cohort 2: Cycle 1 Day 1 and Day 15 and Cycle 2 Day 2 and Day 15
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 Day 1 predose | Cycle 1 Day 15 predose | Cycle 2 Day 2 predose | Cycle 2 Day 15 predose |
|---|
| Cohort 2: T-Cell ALL (1-17 Years) | NA | 0.907 | 0.915 | 0.934 |
,| Cohort 2: T-Cell ALL (18-30 Years) | NA | 0.319 | 0.296 | 0.163 |
,| Cohort 2: T-Cell Lymphoblastic Leukemia (LL) (1-30 Years) | NA | 0.456 | 1.23 | 1.06 |
Dose Limiting Toxicity
To determine the dose limiting toxicity (DLT) of Plitidepsin (Aplidin®) when administered daily x 5 days with a fixed dose of Cytarabine for 5 days every four weeks in patients with relapsed/refractory leukemia. (NCT00780143)
Timeframe: Until disease progression or unacceptable toxicity
| Intervention | Participants (Count of Participants) |
|---|
| Aplidin® | 0 |
Contribution of Dasatinib on Minimal Residual Disease (MRD) After Induction Therapy
Percent of patients MRD Positive (MRD > 0.01%) at End of Induction. (NCT00720109)
Timeframe: At the end of induction therapy (at 5 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 40.7 |
| Standard-risk | 29.2 |
| High-risk | 100.0 |
Event-Free Survival (EFS) of Patients With Standard-risk Disease Treated With Dasatinib in Combination With Intensified Chemotherapy
Event-Free Survival (EFS) curves will be constructed using the Kaplan-Meier life table method with standard errors computed using the method of Peto and Peto. A 1-sided 95% confidence interval for EFS will be constructed. (NCT00720109)
Timeframe: At 3 years
| Intervention | Percent probability (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 79.8 |
| Standard-risk | 83.2 |
| High-risk | 66.7 |
Feasibility and Toxicity of an Intensified Chemotherapeutic Regimen Incorporating Dasatinib for Treatment of Children and Adolescents With Ph+ ALL Assessed by Examining Adverse Events
Number of patients in safety cohort with dose limiting toxicity (DLT)(including treatment delay) (NCT00720109)
Timeframe: Weeks 3 through 23 of treatment (From week 3 Induction through Intensification Block 1)
| Intervention | Pts with DLTs (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 1 |
Overall EFS Rate for the Combined Cohort of Standard- and High-Risk Patients (Who Receive the Final Chosen Dose of Dasatinib)
An event is defined as: Induction failure, relapse at any site, secondary malignancy, or death. (NCT00720109)
Timeframe: From the time entry on study to first event or date of last follow-up, assessed up to 7 years
| Intervention | percentage of patients (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 79.8 |
| Standard-risk | 83.2 |
| High-risk | 66.7 |
Percent of Patients MRD Positive (MRD > 0.01%) at End of Consolidation
A 1-sample Z-test of proportions (alpha=5%, 1-sided test) will be used. (NCT00720109)
Timeframe: At end of consolidation (at 11 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Treatment Induction (Enzyme Inhibitor Therapy & Chemotherapy) | 10.5 |
| Standard-risk | 0 |
| High-risk | 66.7 |
Progression-free Survival Rate
"after autologous stem cell transplantation (ASCT). Disease progression is defined using International Workshop Criteria for non-Hodgkin lymphoma37 and is defined as:~≥ 50% increase in products of diameters of any previously identified abnormal node or nodule AND/OR~appearance of any new lesions" (NCT00521014)
Timeframe: up to 3 years
| Intervention | years (Mean) |
|---|
| Relapsed Follicular Lymphoma Patients | 1.759 |
Maximum Tolerated Dose (MTD) of Clofarabine
Maximum tolerated dose (MTD) defined as the highest dose schedule in which 6 patients were treated with at most 1 experiencing a dose-limiting toxicity (DLT). Clofarabine 15 mg/m2 IV over approximately 1 hour daily (number of days selected based on Phase I portion). (NCT01794702)
Timeframe: After second, 33 day cycle
| Intervention | mg/m^2 x 4 days (6-9) (Number) |
|---|
| Period 1 | 15 |
Number of Participants With a Response
Primary endpoint is overall response defined as the best response either complete response, complete remission without platelet recovery, or complete remission without incomplete blood count recovery within 56 days. (NCT01794702)
Timeframe: 56 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | 20 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT01794702)
Timeframe: Up to 2 years after participants off study date
| Intervention | Months (Median) |
|---|
| Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | 7.7 |
To Determine the Disease-free Survival (DFS).
Time from date of treatment start until the date of first objective documentation of return of disease. (NCT01794702)
Timeframe: Up to 2 years after participants off study date
| Intervention | months (Median) |
|---|
| Phase II Clofarabine + Cytarabine + Decitabine + Idarubicin | 17.9 |
Disease-free Survival
Disease-free survival (DFS) was measured as the interval from achievement of CR until relapse or death, regardless of cause. DFS was estimated using the Kaplan Meier method. (NCT00742625)
Timeframe: Duration of study (up to 10 years)
| Intervention | months (Median) |
|---|
| Bortezomib + Daunorubicin + Cytarabine | 8 |
Overall Survival
Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method. (NCT00742625)
Timeframe: Duration of study (up to 10 years)
| Intervention | months (Median) |
|---|
| Bortezomib + Daunorubicin + Cytarabine | 12 |
Participants Experiencing a Dose-limiting Toxicity (DLT) of Bortezomib When Administered in Combination With Intermediate-dose Cytarabine
"DLTs were considered only during the first cycle of consolidation therapy and included grade 3 or 4 sensory or autonomic neuropathy, persistent grade 4 thrombocytopenia or neutropenia at day 42 in the absence of AML,any grade 4 or 5 nonhematologic toxicity, and any grade 3 nonhematologic toxicity (excluding neuropathy and toxicities secondary to neutropenia and sepsis) that did not resolve to grade 2 by day 42 unless attributable to persistent or recurrent AML. Grade 4 anorexia (requiring total parenteral nutrition) and grade 4 fatigue (requiring bed rest) were not considered DLTs.~Toxicity was graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale is as follows: grade 1: mild; grade 2: moderate; grade 3: Severe; grade 4: Life Threatening; grade 5: Death." (NCT00742625)
Timeframe: during consolidation cycle 1 (42 days)
| Intervention | participants (Number) |
|---|
| Bortezomib (0.7 mg/m^2) + Int-DAC | 0 |
| Bortezomib (1.0 mg/m^2) + Int-DAC | 0 |
| Bortezomib (1.3 mg/m^2) + Int-DAC | 1 |
Remission Induction Response
"Response was calculated according to Revised International Working Group (IWG) criteria for Acute myeloid leukemia (AML)~A response was defined as the portion of participants who achieved a complete response (CR) or CR with incomplete platelet recovery(CRp) during induction.~A CR is defined as those with > 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, <5 % myeloblast cells for bone marrow with peripheral blood and normal complete blood count (absolute neutrophils > 1000 mL and platelets >= 100,000 mL).~A CRp is defined as a CR except platelets < 100,000 mL without need for transfusion." (NCT00742625)
Timeframe: 2 months
| Intervention | participants (Number) |
|---|
| Complete response | Complete response with incomplete platelet recover |
|---|
| Bortezomib + Daunorubicin + Cytarabine | 62 | 4 |
Overall Survival at One Year
The number of participants alive one year after baseline. (NCT00973752)
Timeframe: 1 years
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 19 |
Disease-free Survival
To determine DFS at 1 year post transplant. (NCT00439556)
Timeframe: At 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Velcade Dose Level 1 | 16 |
| Velcade Dose Level 2 | 0 |
| Velcade Dose Level 3 | 0 |
Number of Participants With Dose Limiting Toxicity (DLT)
To determine the maximum tolerated dose(MTD) of velcade and dose limiting toxicity(DLT). A dose limiting toxicity (DLT) was defined as a grade 3-4 neurological toxicity, graft failure, or death due to GvHD. The Commom Terminlogy Criteria for Adverse Events v3.0 was used. (NCT00439556)
Timeframe: From start of treatment to 90 days after the start of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, Transplant, Filgrastim, Tacrolimus) | 0 |
| Velcade Dose Level 2 | 0 |
| Velcade Dose Level 3 | 0 |
3 Year Progression-Free Survival Rate
Percentage of participants out of total treated alive with disease progression 3 years following registration. Progression-free survival (PFS) was measured from the date of study registration to the date of documented disease progression or death of any cause. (NCT00290433)
Timeframe: From registration to disease progression or death, up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| HCVIDDOXIL Regimen | 30 |
Overall Survival (OS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen
Overall Survival (OS) of patients with Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen. OS is defined from the first dose of study drug to the time of death for any reason. (NCT00392990)
Timeframe: At 2 years from treatment initiation Median follow up 34 months (range 15-45)
| Intervention | percentage of patients alive (Number) |
|---|
| High Risk - Treated With Alternating R-CODOX-M/R-IVAC | 81 |
| Low Risk - Treatment With 3 Cycles of R-CODOX-M | 100 |
Progression Free Survival (PFS) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen
Progression Free Survival (PFS) will be defined from the first dose of study drug to the first documentation of progressive disease or death for any reason. Patients that are lost to follow-up before progression will be censored at the point of last documentation of not experiencing the event. (NCT00392990)
Timeframe: At 2 years from treatment initiation. Median follow up 34 months (range 15-45)
| Intervention | percentage of patients progression free (Number) |
|---|
| High Risk - Treated With Alternating R-CODOX-M/R-IVAC | 76 |
| Low Risk - Treatment With 3 Cycles of R-CODOX-M | 100 |
Overall Response Rate (ORR) of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen
"Response Rate is defined as combined number of patients with Complete Remission (CR) Complete Remission undetermined (Cru) and Partial Remission (PR) for patients with Burkitt's and Burkitt-like Lymphoma/Leukemia. Response will be measured by CT scans following treatment completion and assessed using Response Criteria for Non-Hodgkin's Lymphoma where:~CR=complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.~CRu=same as above but allowing for 75% decrease in lymph node masses and indeterminate or normal bone marrow.~PR=50% decrease in SPD of the six largest dominant nodes or nodal masses with no increase in size or other nodes, liver, spleen and no new sites of disease." (NCT00392990)
Timeframe: After two cycles of treatment and at completion of treatment (4 cycles for high risk and 3 cycles for low risk) up to approximately 20 weeks.
| Intervention | percentage of patients (Number) |
|---|
| ORR after two cycles of treatment | ORR at completion of treatment |
|---|
| High Risk - Treated With Alternating R-CODOX-M/R-IVAC | 100 | 100 |
,| Low Risk - Treatment With 3 Cycles of R-CODOX-M | 100 | 100 |
Safety of Patients With Burkitt's and Burkitt-like Lymphoma/Leukemia Treated With Modified Magrath Regimen (Addition of Rituximab, Subsitution of Adriamycin for Doxil and Using Lower Dose of Methotrexate)
"Adverse events (AE) graded as either 3 or 4 and determined to be at least possibly related to study treatment will be collected in patients Burkitt's and Burkitt-like Lymphoma/Leukemia treated with modified Magrath regimen to assess the safety and toxicity profile of the addition of rituximab, subsitution of adriamycin for doxil and lower dose of methotrexate. AEs will be assessed as follows at the following time points: At the end of each cycle or monthly whichever is less frequent and 30 days post last dose of study treatment for a maximum of 3 cycles for regimen A and 4 cycles for regimen B and up to 12 months.~In general AEs will be assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v 3.0). In general adverse events (AEs) will be graded according to the following:~Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE" (NCT00392990)
Timeframe: After each cycle or monthly (whichever is less frequent), 30 days post last dose. Treatment duration was at a median of 13 weeks (range 11-20) for high-risk patients and 10 weeks (range 9-12) for low-risk patients.
| Intervention | participants (Number) |
|---|
| Anemia : Grade 3 | Anemia : Grade 4 | Neutropenia : Grade 3 | Neutropenia : Grade 4 | Thrombocytopenia : Grade 3 | Thrombocytopenia : Grade 4 | Mucositis : Grade 3 | Mucositis : Grade 4 | Infection : Grade 3 | Infection : Grade 4 | Elevated Transaminases : Grade 3 | Elevated Transaminases : Grade 4 | Fever (Neutropenic) : Grade 3 | Fever (Neutropenic) : Grade 4 | Low Phosphate : Grade 3 | Low Phosphate : Grade 4 | Sodium Abnormalities : Grade 3 | Sodium Abnormalities : Grade 4 | Hyperglycemia : Grade 3 | Hyperglycemia : Grade 4 | Hypoalbuminemia : Grade 3 | Hypoalbuminemia : Grade 4 | Hypokalemia : Grade 3 | Hypokalemia : Grade 4 | Cardiac : Grade 3 | Cardiac : Grade 4 | Diarrhea : Grade 3 | Diarrhea : Grade 4 | Elevated Creatinine : Grade 3 | Elevated Creatinine : Grade 4 | Nausea/Vomiting : Grade 3 | Nausea/Vomiting : Grade 4 | Low Blood Pressure : Grade 3 | Low Blood Pressure : Grade 4 | Rash : Grade 3 | Rash : Grade 4 | Edema : Grade 3 | Edema : Grade 4 | Low Magnesium : Grade 3 | Low Magnesium : Grade 4 |
|---|
| High Risk - Treated With Alternating R-CODOX-M/R-IVAC | 13 | 1 | 5 | 6 | 1 | 13 | 7 | 3 | 8 | 0 | 6 | 0 | 4 | 0 | 5 | 0 | 4 | 0 | 1 | 5 | 4 | 0 | 1 | 0 | 3 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
,| Low Risk - Treatment With 3 Cycles of R-CODOX-M | 3 | 0 | 2 | 2 | 1 | 2 | 2 | 0 | 1 | 0 | 2 | 0 | 3 | 0 | 1 | 0 | 2 | 0 | 3 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Relationship of Inhibition of DNA Synthesis and Clinical Response
Clinical response is defined as MRD (minimal residual disease) measured by flow cytometry at day 22. The MRD at day 22 is classified as positive (with MRD) or negative (no detectable MRD). The relation between inhibition of DNA synthesis and MRD was performed by logistic regression. In the model, logit of probability of MRD positive was regressed on inhibition of DNA synthesis. (NCT00136084)
Timeframe: Measurements were assessed in Induction I chemotherapy
| Intervention | Percent inhibition of DNA Synthesis (Mean) |
|---|
| Overall | 66.7 |
To Assess Whether Inhibition of DNA Synthesis is Greater After High-dose Ara-C (HDAC) Than After Low-dose Ara-C (LDAC) Therapy
Inhibition of DNA synthesis is defined as the percentage of DNA synthesis rate at 24-hour post-araC treatment over DNA synthesis rate pre-araC treatment. (NCT00136084)
Timeframe: Measurements were assessed in Induction I chemotherapy
| Intervention | Percent Inhibition of DNA Synthesis (Mean) |
|---|
| Arm 1: (HDAC) | 60.6 |
| Arm 2:(LDAC) | 72.8 |
To Estimate the Overall Event-free Survival (EFS) of AML Patients Who Undergo Risk-adapted and Genotype-directed Therapy
Overall event-free survival (EFS) was defined as the time from study enrollment to induction failure, relapse, secondary malignancy, death, or study withdrawal for any reason, with event-free patients censored on the date of the last follow-up (NCT00136084)
Timeframe: Five Year
| Intervention | Percentage of Participants (Number) |
|---|
| Overall | 62.4 |
Minimal Residual Disease (MRD).
Detection of Minimal Residual Disease following one course of chemotherapy where positive MRD was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells (>=0.1%). (NCT00136084)
Timeframe: Day 22 MRD measurement
| Intervention | participants (Number) |
|---|
| MRD Positive | MRD Negative |
|---|
| Arm 1: (HDAC) | 31 | 68 |
,| Arm 2:(LDAC) | 43 | 63 |
Proportion of Minimal Residual Disease (MRD)+ Patients Who Become MRD- After One Course of Gemtuzumab Ozogamicin (GO)
To estimate the proportion of minimal residual disease (MRD)+ patients who become MRD- after one course of gemtuzumab ozogamicin (GO) (NCT00136084)
Timeframe: Consolidation I
| Intervention | Participants (Number) |
|---|
| Negative | Positive |
|---|
| Overall | 11 | 4 |
Proportion of MRD Reduction After One Course of Cytarabine + Daunomycin + Etoposide (ADE) + GO
To estimate proportion of patients with MRD reduction after one course of Induction II (cytarabine + daunomycin + etoposide (ADE) + GO), who had no response to first course of induction therapy. (NCT00136084)
Timeframe: Induction II
| Intervention | Participants (Number) |
|---|
| Decrease | Increase or no change |
|---|
| Overall | 27 | 2 |
Proportion of Patients Experienced Toxicity of Cytarabine + Daunomycin + Etoposide (ADE) + GO.
To estimate proportion of patients experiencing CTC Grade 3 or 4 toxicity during Induction II (Cytarabine + Daunomycin + Etoposide (ADE) + GO), who had no response to first course of induction therapy (NCT00136084)
Timeframe: Induction II
| Intervention | Participants (Number) |
|---|
| Experienced Grade 3 or 4 toxicities | Did not experience Grade 3 or 4 toxicities |
|---|
| Overall | 27 | 3 |
Number of Participants Who Died or Were Censored by 24 Months
This measure (time to death or censor) was defined for all enrolled subjects from the date of randomization until death from any cause. If a subject was not known to have died by the end of the followup period, observation of overall survival was censored on the date the patient was last known to be alive. The number of participants who died or were censored is presented here. (Note: all subjects participating in this study had either died or were censored by 24 months.) (NCT00513305)
Timeframe: From Baseline through 24 months following Baseline
| Intervention | Participants (Number) |
|---|
| Low-dose Cytarabine Plus Arsenic Trioxide | 33 |
| Low-dose Cytarabine Alone | 34 |
Number of Participants Who Experienced Early Death
Early death is defined as death from any cause within the first 14 days after start of study drug treatment. The number of patients in each study group who experienced early death is presented here. (NCT00513305)
Timeframe: 14 days from start of study drug treatment
| Intervention | Participants (Number) |
|---|
| Low-dose Cytarabine Plus Arsenic Trioxide | 0 |
| Low-dose Cytarabine Alone | 2 |
Number of Participants Who Experienced Induction (Thirty-Day) Mortality
The number of subjects who died from any cause within the first 30 days after the start of study drug treatment is presented here. (NCT00513305)
Timeframe: Up to 30 days following start of study drug treatment
| Intervention | Participants (Number) |
|---|
| Low-dose Cytarabine Plus Arsenic Trioxide | 3 |
| Low-dose Cytarabine Alone | 2 |
Percentage of Participants in Complete Remission (CR)
The primary efficacy variable was the percentage of subjects in each treatment group who achieved complete remission after treatment with study drug. Complete remission was defined as: 1) Less than 5% blasts in normocellular bone marrow sample. 2) No blasts in bone marrow sample containing Auer rods. 3)Clearance of previous extramedullary disease. 4)Normal values for absolute neutrophil count (at least 1000/microliter), platelet count (at least 100,000/microliter), without platelet transfusions, and in absence of peripheral myeloblasts. (NCT00513305)
Timeframe: From baseline through Day 70. Assessments were performed on Day 21 in cycle 1, no later than Day 56 of cycle 1 or 2 (if applicable), and no later than Day 70 of cycle 1 or 2 (if applicable) or at any other time at the discretion of the investigator
| Intervention | Percentage of participants in CR (Number) |
|---|
| Low-dose Cytarabine Plus Arsenic Trioxide | 15.2 |
| Low-dose Cytarabine Alone | 8.8 |
Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate
The duration of overall survival was defined for all patients and was measured from the date of randomization until death from any cause. For a patient who was not known to have died by the end of the follow-up period, observation of overall survival was censored on the date the patient was last known to be alive. The estimate of likelihood of survival at 6 and 12 months after Baseline using the Kaplan Meier Estimate is presented here. (NCT00513305)
Timeframe: Baseline through 12 months
| Intervention | Proportion of Participants (Number) |
|---|
| Month 6 (95% Confidence Interval) | Month 12 (95% Confidence Interval) |
|---|
| Low-dose Cytarabine Alone | 0.649 | 8.51 |
,| Low-dose Cytarabine Plus Arsenic Trioxide | 0.626 | 12.22 |
Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate
RFS is defined for patients who achieved a complete remission (CR), complete remission with incomplete platelet recovery (CRp), or partial remission(PR), and was measured from the date of attaining CR, CRp, or PR until the date of AML relapse or death from any cause, whichever occurred first. For a patient not known to have relapsed or died by the end of the study followup, observation of relapse free survival was censored on the date of the last followup examination. The Kaplan Meier Estimate of relapse-free survival at Month 3 and Month 6 is presented here. (NCT00513305)
Timeframe: From Baseline (randomization) through 24 months following Baseline
| Intervention | Proportion of participants (Number) |
|---|
| Month 3 (95% Confidence Interval) | Month 6 (95% Confidence Interval) |
|---|
| Low-dose Cytarabine Alone | 0.800 | 0.800 |
,| Low-dose Cytarabine Plus Arsenic Trioxide | 0.818 | 0.818 |
Event Free Survival. EFS
Percentage of patients who were event free at 3 years among those on Standard VCR dosing who did not undergo Hematopoietic Stem Cell Transplant (SCT). (NCT00381680)
Timeframe: 3 years after enrollment
| Intervention | percentage of participants EFS at 3 yrs3 (Number) |
|---|
| Regimen A: Standard Vincristine Dosing | 66.0 |
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1
Percentage of patients who had minimal residual disease (MRD) < 0.01% among those with isolated BM or combined BM relapse >= 36 months and had successful MRD determinations at End Block 1 (NCT00381680)
Timeframe: End of Block 1 (35 days) of Induction therapy
| Intervention | percentage of participants (Number) |
|---|
| Regimen A | 50.8 |
| Regimen B | 41.5 |
Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3
Percentage of patients who had minimal residual disease (MRD) < 0.01% among those with isolated BM or combined BM relapse >= 36 months and had successful MRD determinations at End Block 3. (NCT00381680)
Timeframe: End of Block 3 (105 days) of Induction therapy
| Intervention | percentage of participants (Number) |
|---|
| Regimen A | 81.4 |
| Regimen B | 88.9 |
Adjusted Event Free Survival
Adjusted percentage of patients who were event free at 3 years. For patients who received matched donor SCT, EFS was adjusted to start from the actual SCT date. For patients who did not undergo SCT, EFS was adjusted to start from median time to SCT based on patients who received matched related SCT (where patients who had events prior to SCT date were excluded from the calculation of median time to SCT). (NCT00381680)
Timeframe: 3 years
| Intervention | adjusted percentage of participants (Number) |
|---|
| Received SCT | Did not receive SCT |
|---|
| Regimen A: Standard Vincristine Dosing | 82.2 | 64.2 |
Event Free Survival (EFS)
Percentage of patients who were event free at 3 years among those with isolated BM or combined BM relapse >= 36 months. (NCT00381680)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| MRD < 0.01% BL1 | MRD >= 0.01% BL1 | MRD < 0.01% BL3 | MRD >= 0.01% BL3 |
|---|
| Regimen A | 88.5 | 60.0 | 83.8 | 61.5 |
,| Regimen B | 77.3 | 46.2 | 83.3 | 33.3 |
Frequency and Severity of Adverse Effects
Percentage of patients who developed at least 1 episode of grade 2 to 4 neuropathy. (NCT00381680)
Timeframe: Up to 107 weeks
| Intervention | percentage of participants (Number) |
|---|
| CC or CT genotype | High-risk CEP72 genotype (TT at rs924607) |
|---|
| All Patients | 17.3 | 44.4 |
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant (NCT00333840)
Timeframe: 144 months
| Intervention | Participants (Number) |
|---|
| Imatinib (STI571) | 226 |
| IFN-a + Ara-C | 163 |
Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant (NCT00333840)
Timeframe: 144 months
| Intervention | Participants (Number) |
|---|
| Imatinib to IFN-a + Ara-C | 2 |
| IFN-a + Ara-C to Imatinib | 160 |
Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
"Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:~progression to Accelerated Phase (AP) or Blast Crisis (BC)~loss of Complete Hematological Response (CHR)~loss of Major Cytogenetic Response (MCyR) confirmed~loss of Major Cytogenetic Response (MCyR) unconfirmed~increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)~death (due to any cause when reported as primary reason for discontinuation of treatment).~Kaplan Meier estimates of the percentage of participants with Event Free Survival at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment." (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 505, 332) | 36 months (n = 448, 263) | 48 months (n = 415, 241) | 60 months (n = 395, 223) | 72 months (n = 376, 207) | 84 months (n = 352, 181) | 96 months (n = 334, 166) | 108 months (n = 301, 141) | 120 months (n = 269, 130) | 132 months (n = 257, 124) | 144 months (n = 143, 76) |
|---|
| IFN-a + Ara-C | 79.4 | 70.0 | 67.0 | 63.7 | 61.9 | 60.1 | 59.0 | 58.3 | 56.6 | 56.6 | 56.6 | 51.8 |
,| Imatinib (STI571) | 96.6 | 89.6 | 85.3 | 83.9 | 83.2 | 83.0 | 82.0 | 81.0 | 79.9 | 79.6 | 79.6 | 79.6 |
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
Time to progression to AP/BC is defined as the time between randomization and either of the following events on treatment: death (due to CML when reported as primary reason for discontinuation of treatment) or progression to Accelerated Phase or Blast Crisis and is censored at last examination date for patients without event. No data after discontinuation of study treatment was included. The Kaplan Meier estimates of the percentage of participants with survival without progression to AP/BC at the given time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 513, 388) | 36 months (n = 461, 337) | 48 months (n = 431, 311) | 60 months (n = 409, 289 ) | 72 months (n = 384, 265) | 84 months (n = 358, 236) | 96 months (n = 338, 220) | 108 months (n = 305, 189) | 120 months (n = 272, 175) | 132 months (n = 259, 165) | 144 months (n = 145, 94) |
|---|
| IFN-a + Ara-C | 92.9 | 90.0 | 87.9 | 84.7 | 83.5 | 83.1 | 82.4 | 82.4 | 82.4 | 82.4 | 82.4 | 82.4 |
,| Imatinib (STI571) | 98.5 | 95.7 | 94.0 | 93.1 | 92.7 | 92.7 | 92.7 | 92.4 | 92.1 | 92.1 | 92.1 | 92.1 |
Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 553, 553) | 24 months (n = 542, 512) | 36 months (n = 518, 471) | 48 months (n = 492, 441) | 60 months (n = 475, 411) | 72 months (n = 461, 388) | 84 months (n = 446, 373) | 96 months (n = 430, 358) | 108 months (n = 391, 315) | 120 months (n = 368, 299) | 132 months (n = 356, 288) | 144 months (n = 250, 199) |
|---|
| IFN-a + Ara-C | 97.7 | 93.6 | 89.8 | 87.7 | 85.4 | 83.8 | 83.1 | 81.4 | 79.9 | 78.8 | 77.7 | 75.4 |
,| Imatinib (STI571) | 98.9 | 96.0 | 92.4 | 90.4 | 89.4 | 88.2 | 86.6 | 85.4 | 84.3 | 83.3 | 82.8 | 81.3 |
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
"Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Philadelphia chromosome positive (Ph+) metaphases) and amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.~Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % of Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Major Cytogenic Response | Complete Cytogenic Response | Partial Cytogenic Response |
|---|
| IFN-a + Ara-C | 23.3 | 11.6 | 11.8 |
,| Imatinib (STI571) | 89.0 | 82.8 | 6.1 |
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
"Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Ph chromosome (Ph+) containing metaphases) and the amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.~Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Major Cytogenic Response | Complete Cytogenic Response | Partial Cytogenic Response |
|---|
| IFN-a + Ara-C to Imatinib | 86.0 | 81.0 | 5.0 |
,| Imatinib to IFN-a + Ara-C | 14.3 | 7.1 | 7.1 |
Percentage of Participants With Event Free Survival Events (All Randomized Participants)
"Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:~progression to Accelerated Phase (AP) or Blast Crisis (BC)~loss of Complete Hematological Response (CHR)~loss of Major Cytogenic Response (MCyR) confirmed~loss of Major Cytogenic Response (MCyR) unconfirmed~increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)~death (due to any cause when reported as primary reason for discontinuation of treatment).~The percentage of participants with Event Free Survival events in each category was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment." (NCT00333840)
Timeframe: 144 months
| Intervention | Percentage of participants (Number) |
|---|
| Participants with events | Progression to AP or BC | Loss of CHR | Loss of MCyR (confirmed) | Loss of MCyR (unconfirmed) | Increase of WBC | Death |
|---|
| IFN-a + Ara-C | 32.2 | 12.8 | 7.6 | 5.4 | 1.1 | 3.4 | 1.8 |
,| Imatinib (STI571) | 17.9 | 6.9 | 2.7 | 4.2 | 0.9 | 0.2 | 3.1 |
Percentage of Participants With Major Molecular Response (First-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n= 305, 83) | 24 months (n= 102, 12) | 36 months (n= 68, 7) | 48 months (n= 305, 12) | 60 months (n= 316, 10) | 72 months (n= 292, 9) | 84 months (n= 247, 8) | 96 months (n= 228, 4) | 108 months (n= 233, 0) | 120 months (n= 204, 0) | 132 months (n= 168, 0) | 144 months (n= 1, 0) |
|---|
| IFN-a + Ara-C | 9.6 | 25.0 | 28.6 | 58.3 | 100.0 | 88.9 | 87.5 | 100.0 | NA | NA | NA | NA |
,| Imatinib (STI571) | 50.2 | 69.6 | 76.5 | 77.0 | 88.0 | 88.0 | 91.9 | 92.5 | 93.6 | 93.1 | 92.3 | 100.0 |
Percentage of Participants With Major Molecular Response (Second-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale. (NCT00333840)
Timeframe: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
| Intervention | Percentage of participants (Number) |
|---|
| 12 months (n = 86) | 24 months (n = 62) | 36 months (n = 130) | 48 months (n = 216) | 60 months (n = 174) | 72 months (n = 146) | 84 months (n = 139) | 96 months (n = 138) | 108 months (n = 120) | 120 months (n = 84) | 132 months (n = 31) | 144 months |
|---|
| IFN-a + Ara-C to Imatinib | 51.2 | 69.4 | 78.5 | 81.9 | 86.2 | 91.1 | 86.3 | 87.0 | 90.0 | 85.7 | 90.3 | NA |
Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
"Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first.~See Outcome #3 for definition of CR and CRi.~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 12 to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 8.1 |
| Placebo and Cytarabine | 7.0 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 5.7 |
| Placebo and Cytarabine - In Stratum < 6 Months | 6.7 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 10.3 |
| Placebo and Cytarabine In Stratum >= 6 Months | 9.1 |
Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
"Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first.~See Outcome #3 for definition of CR and CRi.~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 12 to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 9.5 |
| Placebo and Cytarabine | 7.0 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 6.7 |
| Placebo and Cytarabine - In Stratum < 6 Months | 6.7 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 15.4 |
| Placebo and Cytarabine In Stratum >= 6 Months | 9.2 |
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)
"DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first.~CR is defined on morphologic criteria at a single response assessment:~a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis;~absence of Auer rods in the blasts that are present;~absence of extramedullary disease;~absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping;~only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow;~recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L).~CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L)." (NCT00317642)
Timeframe: Day 12 to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 7.6 |
| Placebo and Cytarabine | 3.8 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 5.7 |
| Placebo and Cytarabine - In Stratum < 6 Months | 6.3 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 11.5 |
| Placebo and Cytarabine In Stratum >= 6 Months | 3.8 |
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)
"DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first.~CR is defined on morphologic criteria at a single response assessment:~a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis;~absence of Auer rods in the blasts that are present;~absence of extramedullary disease;~absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping;~only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow;~recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L).~CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L)." (NCT00317642)
Timeframe: Day 12 to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 7.7 |
| Placebo and Cytarabine | 3.8 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 6.7 |
| Placebo and Cytarabine - In Stratum < 6 Months | 6.3 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 10.2 |
| Placebo and Cytarabine In Stratum >= 6 Months | 3.8 |
Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
"Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first.~Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts).~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 1 (randomization) up to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 1.9 |
| Placebo and Cytarabine | 1.0 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 1.4 |
| Placebo and Cytarabine - In Stratum < 6 Months | 1.0 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 2.0 |
| Placebo and Cytarabine In Stratum >= 6 Months | 1.0 |
Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
"Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first.~Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts).~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 1 (randomization) up to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 1.9 |
| Placebo and Cytarabine | 1.0 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 1.1 |
| Placebo and Cytarabine - In Stratum < 6 Months | 1.0 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 2.8 |
| Placebo and Cytarabine In Stratum >= 6 Months | 1.0 |
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
"Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first.~Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts).~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 1 (randomization) to Day 122
| Intervention | percentage of participants (Number) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 37.7 |
| Placebo and Cytarabine | 16.6 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 35.2 |
| Placebo and Cytarabine - In Stratum < 6 Months | 16.9 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 40.5 |
| Placebo and Cytarabine In Stratum >= 6 Months | 16.2 |
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
"Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first.~Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts).~Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease." (NCT00317642)
Timeframe: Day 1 (randomization) to Day 122
| Intervention | percentage of participants (Number) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 38.9 |
| Placebo and Cytarabine | 17.1 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 31.4 |
| Placebo and Cytarabine - In Stratum < 6 Months | 17.9 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 47.4 |
| Placebo and Cytarabine In Stratum >= 6 Months | 16.2 |
Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 calculated strata. OS was defined as the number of months from date of randomization until date of death due to any cause. (NCT00317642)
Timeframe: Day 1 (randomization) up to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | 6.6 |
| Placebo and Cytarabine (FAS) | 6.4 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 5.1 |
| Placebo and Cytarabine - In Stratum < 6 Months | 5.5 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 8.7 |
| Placebo and Cytarabine In Stratum >= 6 Months | 7.2 |
Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause. (NCT00317642)
Timeframe: Day 1 (randomization) up to approximately 4 years
| Intervention | months (Median) |
|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | 6.6 |
| Placebo and Cytarabine (FAS) | 6.3 |
| Clofarabine and Cytarabine - In Stratum < 6 Months | 4.8 |
| Placebo and Cytarabine - In Stratum < 6 Months | 6.3 |
| Clofarabine and Cytarabine In Stratum >= 6 Months | 9.7 |
| Placebo and Cytarabine In Stratum >= 6 Months | 6.6 |
Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)
"Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003).~CR is defined on morphologic criteria at a single response assessment:~a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis;~absence of Auer rods in the blasts that are present;~absence of extramedullary disease;~absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping;~only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow;~recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L).~CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L)." (NCT00317642)
Timeframe: Day 12 up to approximately 6 months
| Intervention | percentage of participants (Number) |
|---|
| Overall Remission (CR + CRi) | Complete Remission (CR) | CR with incomplete blood count recovery (CRi) |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 46.9 | 35.2 | 11.7 |
,| Clofarabine and Cytarabine - In Stratum < 6 Months | 45.5 | 33.0 | 12.5 |
,| Clofarabine and Cytarabine In Stratum >= 6 Months | 48.6 | 37.8 | 10.8 |
,| Placebo and Cytarabine | 22.9 | 17.8 | 5.1 |
,| Placebo and Cytarabine - In Stratum < 6 Months | 22.9 | 18.1 | 4.8 |
,| Placebo and Cytarabine In Stratum >= 6 Months | 23.0 | 17.6 | 5.4 |
Participants With Adverse Events (CSR 7-April-11)
"Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine.~Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death" (NCT00317642)
Timeframe: Day 1 up to a maximum of 4 years (includes up to a maximum of 3 cycles of therapy plus 45 days follow up. Related AEs are followed to resolution.)
| Intervention | participants (Number) |
|---|
| Any Treatment Emergent AE | Any Related Treatment Emergent AE | Any Treatment Emergent Grade >=3 AE | Any Related Treatment Related Grade >=3 AE | Discontinue of study medication due to AE | Discontinue of study medication due to related AE |
|---|
| Clofarabine (IV Formulation) and Cytarabine | 161 | 157 | 157 | 127 | 17 | 14 |
,| Placebo and Cytarabine | 155 | 133 | 133 | 83 | 5 | 3 |
>80% Inhibition of FLT3 Phosphorylation in a Majority of Post-treatment Trough Time Points
FLT3 inhibition is determined in patients receiving lestaurtinib by measuring FLT3 plasma inhibitory activity (PIA). For PIA predictive modeling, a random effects linear regression model will be used to describe the relationship between PIA and Pharmacokinetic (PK) levels for each of the 5 trough plasma samples collected for each patient (NCT00469859)
Timeframe: Course 1 day 7, day 14, day 21, and day 28.
| Intervention | participants (Number) |
|---|
| Group 1 (Lestaurtinib Dose 50 mg/m2 | 5 |
| Group 2 (Lestaurtinib: Dose 62.5 mg/m2 | 5 |
Dose-limiting Toxicity
Number of patients with dose-limiting toxicity (DLT) (NCT00469859)
Timeframe: 28 days
| Intervention | participants (Number) |
|---|
| Group 1 (Lestaurtinib Dose 50 mg/m2 | 0 |
| Group 2 (Lestaurtinib: Dose 62.5 mg/m2 | 0 |
Event-Free Survival Probability During the 3 Years After Transplant
Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood's formula for standard error. (NCT00288626)
Timeframe: 3 years
| Intervention | Probability (Number) |
|---|
| HDIT and HCT | 0.784 |
Event-Free Survival Probability During the 5 Years After Transplant
Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood's formula for standard error. (NCT00288626)
Timeframe: 5 years
| Intervention | Probability (Number) |
|---|
| HDIT and HCT | 0.692 |
Percent of Participants Who Experienced All-Cause Morbidity Within 12 Months of Post-HCT
Morbidity is the occurrence of NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 adverse event grade 3 or higher. (NCT00288626)
Timeframe: From the time of Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) to 1 year after HCT.
| Intervention | Percentage of Participants (Number) |
|---|
| HDIT and HCT | 95.8 |
Percent of Participants Who Experienced All-Cause Morbidity
Morbidity is the occurrence of NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 adverse event grade 3 or higher. (NCT00288626)
Timeframe: From the time of enrollment until completion of the 5-year follow-up, an average of 6 years.
| Intervention | percentage of participants (Number) |
|---|
| HDIT and HCT | 100 |
Time to Neutrophil Engraftment
Neutrophil engraftment, or neutrophil count recovery, is defined as an Absolute Neutrophil Count (ANC) > 500/ μL for 2 consecutive measurements on different days. Normal range is 1500 to 8000/μL. Reference: http://www.medicinenet.com (NCT00288626)
Timeframe: From time of graft infusion to time of engraftment, up to 6 years
| Intervention | Days (Mean) |
|---|
| HDIT and HCT | 10.8 |
Time to Platelet Engraftment
Platelet engraftment, or platelet count recovery, is defined as Platelets > 20,000/μL for two consecutive measurements on different days with no platelet transfusions in the preceding 7 days. Normal range is 150,000-450,000/μL. Reference: http://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/centers_excellence/womens_cardiovascular_health_center/patient_information/health_topics/platelets.html. (NCT00288626)
Timeframe: From time of graft infusion to time of engraftment, up to 6 years
| Intervention | Days (Mean) |
|---|
| HDIT and HCT | 18.5 |
Change From Baseline in Extended Disability Status Scale (EDSS)
Kurtzke's Expanded Disability Status Scale (EDSS) assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS). Change from baseline was computed as the value at the time point minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening. A change of > 0.5 in EDSS was a treatment-failure criterion. (NCT00288626)
Timeframe: 6 months to 5 years after HCT
| Intervention | units on a scale (Mean) |
|---|
| 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | -0.3 | -0.7 | -0.8 | -0.8 | -0.6 | -0.9 |
Change From Baseline in Number of Gadolinium-Enhanced Lesions
Multiple sclerosis disease-related lesions were assessed by gadolinium-enhanced magnetic resonance imaging (MRI). Change from baseline was computed as the value at the time point minus the baseline value. A negative value in change from baseline indicates an improvement and a positive value indicates worsening. (NCT00288626)
Timeframe: 8 weeks to 5 years after HCT
| Intervention | Lesions per scan (Mean) |
|---|
| 8 Weeks Post Transplant | 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | -2.1 | -2.3 | -2.5 | -2.5 | -1.3 | -2.2 | -2.7 |
Change From Baseline in T1-Weighted Lesion Volume
A T1-weighted magnetic resonance imaging (MRI) scan was used to assess the volume of T1 lesions in the brain. Change from baseline was computed as the value at the time point minus the baseline value. (NCT00288626)
Timeframe: 8 weeks to 5 years after HCT
| Intervention | milliliter (Mean) |
|---|
| 8 Weeks Post Transplant | 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | -0.1 | 0.0 | 0.2 | 0.3 | 0.4 | 0.4 | 0.3 |
Change From Baseline in T2-Weighted Lesion Volume
A T2-weighted magnetic resonance imaging (MRI) scan was used to assess the volume of T2 lesions in the brain. Change from baseline was computed as the value at the time point minus the baseline value. (NCT00288626)
Timeframe: 8 weeks to 5 years after HCT
| Intervention | milliliters (Mean) |
|---|
| 8 Weeks Post Transplant | 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | -0.8 | -0.7 | -1.0 | -1.6 | -1.9 | -1.9 | -2.3 |
Disease-Modifying Therapy Survival Probability After Transplant
Treatment with disease-modifying therapy was measured by the number of days from transplant to the first treatment with an additional disease-modifying therapy. Examples of therapy include interferon beta-1a, glatiramer acetate, natalizumab, alemtuzumab, other immunosuppressive medications, or experimental therapies directed against MS activity. Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood's formula for standard error. (NCT00288626)
Timeframe: 1 to 5 years after HCT
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 1.0 | 1.0 | 1.0 | 1.0 | 0.950 |
Event-Free Survival Probability After Transplant
Event-free survival (EFS) is survival without death or disease activity from any one of the following criteria: 1) loss of neurological function, defined as a change in pretransplant Extended Disability Status Scale (EDSS) of > 0.5. 2) Relapse, defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit/disability, and lasting over 48 hours. 3) New lesions on magnetic resonance imaging (MRI), defined as presence of 2 or more independent multiple sclerosis brain lesions detected on MRI 1 year or more after stem cell transplant. Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood's formula for standard error. (NCT00288626)
Timeframe: 1, 2, and 4 years after HCT
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 4 Years Post Transplant |
|---|
| HDIT and HCT | 0.958 | 0.828 | 0.738 |
MRI Activity-Free Survival Probability After Transplant
MS disease activity is measured as days from transplant to first occurrence of >= 2 new MS lesions on Magnetic resonance imaging (MRI) relative to baseline. Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood's formula for standard error. (NCT00288626)
Timeframe: 1 to 5 years after HCT
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 0.958 | 0.958 | 0.958 | 0.910 | 0.863 |
MS Progression-Free Survival Probability After Transplant
"MS progression is measured as number of days from transplant to first Kurtzke's Expanded Disability Status Scale (EDSS) increase of more than 0.5 relative to the baseline measurement. EDSS assesses disability in Multiple Sclerosis patients. Eight functional systems are evaluated: visual, brain stem, pyramidal, cerebellar, sensory, bowel and bladder, cerebral, and ambulation. The overall score ranges from 0 (normal neurological exam) to 10 (death due to MS).~Kaplan-Meier estimates of survival probability, with 90% confidence intervals based on Greenwood's formula for standard error." (NCT00288626)
Timeframe: 1 to 5 years after HCT
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 1.0 | 0.913 | 0.913 | 0.913 | 0.913 |
MS Relapse-Free Survival Probability After Transplant
"MS clinical relapse is defined as the development of a new neurological sign and corresponding symptom, or worsening of an existing neurological sign and symptom, localized to central nervous system white matter, resulting in neurological deficit or disability, and lasting over 48 hours. Clinical relapse was determined by the participant's neurologist and was measured as days from transplant to new or worsening neurological symptom relative to baseline.~Kaplan-Meier estimates of survival probability, with 90% confidence interval based on Greenwood's formula for standard error." (NCT00288626)
Timeframe: 1 to 5 years after HCT
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 0.958 | 0.915 | 0.869 | 0.869 | 0.869 |
Number of New T2-Weighted Lesions From Baseline
A T2-weighted magnetic resonance imaging (MRI) scan was used to determine the number of new T2 lesions in the brain relative to Baseline. A value of 0 means that the participant didn't worsen. Values greater than 0 indicate an increase in disease activity from baseline. (NCT00288626)
Timeframe: 6 Months to 5 years after HCT
| Intervention | Lesions per scan (Mean) |
|---|
| 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 0.2 | 0.2 | 0.2 | 0.1 | 0.4 | 0.1 |
Overall Survival
The probability that a participant did not experienced a death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood's formula for standard error was used to calculate 90% confidence intervals. Participants that did not die were censored at the time of last follow-up. (NCT00288626)
Timeframe: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 1.0 | 1.0 | 0.957 | 0.911 | 0.863 |
Percent Change From Screening in Brain Volume
Magnetic resonance imaging (MRI) scan techniques measured ventricular volumes and grey and white matter brain volumes. Change from screening was computed as the value at the time point minus the screening value. (NCT00288626)
Timeframe: 8 weeks to 5 years after HCT
| Intervention | Percent Change (Mean) |
|---|
| 8 Weeks Post Transplant | 6 Months Post Transplant | 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | -0.8 | -1.1 | -1.2 | -1.6 | -2.2 | -2.0 | -2.3 |
Survival From MS-Related Mortality
The probability that a participant did not experienced a MS-related death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood's formula for standard error was used to calculate 90% confidence intervals. Participants that did not experience a MS-related death were censored at the time of last follow-up. A MS-related death was defined as death that occurred at any time after study entry and that was possibly, probably, or definitely related to disease progression. (NCT00288626)
Timeframe: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 1.0 | 1.0 | 0.957 | 0.957 | 0.906 |
Survival From Treatment-Related Mortality
The probability that a participant did not experienced a treatment-related death estimated at 1, 2, 3, 4, and 5 years following transplant via the Kaplan-Meier Method. Greenwood's formula for standard error was used to calculate 90% confidence intervals. Participants that did not experience a treatment-related death were censored at the time of last follow-up. A treatment-related death was defined as death that occurred at any time after study entry and that was possibly, probably, or definitely related to the cellular product or possibly, probably, or definitely related to mobilization of autologous peripheral blood hematopoietic progenitor cells with G-CSF and prednisone or to the high-dose immunosuppressive therapy. There were no treatment-related mortality events in the study. (NCT00288626)
Timeframe: From study entry to death, loss to follow-up, or the end of the study, whichever came first, up to 6 years
| Intervention | Probability (Number) |
|---|
| 1 Year Post Transplant | 2 Years Post Transplant | 3 Years Post Transplant | 4 Years Post Transplant | 5 Years Post Transplant |
|---|
| HDIT and HCT | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
Response
Any patient who is enrolled and receives at least one dose of cytarabine will be considered evaluable for response if (1) the patient demonstrates progressive disease while on protocol therapy or (2) the patient is observed on protocol therapy for at least one cycle. Patients who achieve a complete or partial response according to the RECIST (Response Evaluation Criteria In Solid Tumors) criteria will be considered responders for the study design. All other patients who are evaluable for response will be considered non-responders for the study. (NCT00470275)
Timeframe: the first six cycles of study chemotherapy (126 days)
| Intervention | participants (Number) |
|---|
| Non Responder | Responder |
|---|
| Cytarabine | 10 | 0 |
Maximum Tolerated Dose of Bortezomib (Phase I)
Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperCVAD in patients with untreated aggressive mantle cell lymphoma. (NCT00477412)
Timeframe: Cycle 1 Day 1 - End of Cycle 2 up to 60 days.
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1 Maximum Tolerated Dose (MTD) | 1.3 |
Number of Participants With Overall Response Rate
Response rate is determined by CT scans of the chest, abdomen, and pelvis, unilateral BM biopsy and aspirate with lymphoma markers (if initially positive) and colonoscopy/endoscopy if applicable. (NCT00477412)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase II- Treatment (Combination Chemotherapy) | 87 |
Overall Survival
Overall survival is the time in number of months from start of study treatment to date of death due to any cause. (NCT00477412)
Timeframe: Date of diagnosis to last known date of survival, up to 5 years
| Intervention | months (Median) |
|---|
| Phase II- Treatment (Combination Chemotherapy) | 44 |
Time to Failure (Phase II)
Failure will be defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema will be used to monitor severe toxicity profile in combined therapy. Severe toxicity is defined as at least two episodes of neutropenic fever during treatment courses. (NCT00477412)
Timeframe: First date of diagnosis up to 5 years
| Intervention | months (Median) |
|---|
| Phase II- Treatment (Combination Chemotherapy) | 55 |
Number of Patients With Complete or Partial Response at Day 30
Definition of disease status is based on the article of Revised Response Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al, 2007). Tests used for evaluation of disease status would be physical examination, laboratory testing, bone marrow testing, bone marrow biopsy and aspirate, PET scan, and CT scans of neck, chest, abdomen and pelvis as indicated. (NCT02366663)
Timeframe: Day 0 to Day +30 post-HCT
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (ZBEAM) | 1 |
| Arm II (BEAM) | 1 |
Time to Neutrophil Engraftment
Time to neutrophil engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated. (NCT02366663)
Timeframe: Day 0 to Day 100 post-HCT
| Intervention | days (Median) |
|---|
| Arm I (ZBEAM) | 11 |
| Arm II (BEAM) | 10 |
Time to Platelet Engraftment
Time to platelet engraftment will be compared between treatment arms using a log-rank test, and the cumulative incidence curves will be estimated. (NCT02366663)
Timeframe: Day 0 to Day 100 post-HCT
| Intervention | days (Median) |
|---|
| Arm I (ZBEAM) | 22.5 |
| Arm II (BEAM) | 26 |
Number of Patients With Grade 3-5 Toxicities Graded by the NCI CTCAE Version 4.0
Observed toxicities will be summarized in terms of type and severity. In accordance with the secondary study objectives, descriptive analyses on these data will be performed. (NCT02366663)
Timeframe: Day -21 to Day +100 post-HCT
| Intervention | Participants (Count of Participants) |
|---|
| Anemia | Febrile neutropenia | Hyperglycemia | Hyponatremia | INR increased | Lymphocyte count decreased | Mucositis oral | Neutrophil count decreased | Obesity | Oral pain | Pharyngeal mucositis | Platelet count decreased | Sore Throat | White blood cell decreased |
|---|
| Arm I (ZBEAM) | 2 | 2 | 1 | 1 | 1 | 2 | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 2 |
,| Arm II (BEAM) | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Clinical Response to Crenolanib With Standard Salvage Chemotherapy
To determine the response rate to crenolanib. Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L. CRi response included all CR criteria met, except participant did not have either platelet recovery or ANC recovery. CRh response included all CR criteria met, except subject only has partial platelet recovery and ANC recovery. Complete CR (CRc) response includes all subjects who achieve a CR, CRi and CRh. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but >5%. Morphologic Leukemia-Free State (MLFS) response included ≤5% in % blasts in the BM aspirate or biopsy. (NCT02626338)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Composite complete remission (CR+CRh+CRi) | MLFS | Clinical benefit (CRc+PR+MLFS) |
|---|
| All Subjects | 7 | 3 | 7 |
,| Arm A: HAM Chemotherapy | 3 | 2 | 3 |
,| Arm B: FLAG-Ida Chemotherapy | 4 | 0 | 4 |
,| Arm C: MEC Chemotherapy | 0 | 1 | 0 |
Event-free Survival (EFS)
"Event-free survival is defined as the time from randomization to the date of progressive disease (PD), confirmed morphologic relapse from CR or CRi, treatment failure (failure to achieve CR, CRi or morphologic leukemia free state (MLFS) after at least 6 cycles of study treatment), or death from any cause, assessed by the investigator according to the modified IWG criteria.~PD:~> 50% increase in marrow blasts (minimum 15% increase required if blasts < 30% at baseline); or persistent marrow blast > 70% for ≥ 3 months; without at least a 100% improvement in ANC to an absolute level > 0.5 × 10⁹/L, and/or platelets to > 50 × 10⁹/L non-transfused; or~50% increase in peripheral blasts to > 25 × 10⁹/L; or~New extramedullary disease~Participants with no events prior to the cut-off date were censored at their last assessment date; participants with no events prior to post-treatment therapy initiated before the cut-off date were censored on the start date of post-treatment therapy." (NCT03069352)
Timeframe: From randomization until the primary analysis cut-off date of February 15, 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
| Intervention | months (Median) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 2.0 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 4.7 |
Overall Survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology. (NCT03069352)
Timeframe: From randomization until the primary analysis cut-off date of February 15 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
| Intervention | months (Median) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 4.1 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 7.2 |
Overall Survival After an Additional 6-Months Follow-up
Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology. (NCT03069352)
Timeframe: From randomization until the 6-month follow-up analysis cut-off date of August 15, 2019; the median follow-up time was 17.7 months (range: 0.2-20.8) in the placebo arm and 17.5 months (range: 0.1-23.5) in the venetoclax arm.
| Intervention | months (Median) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 4.1 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 8.4 |
Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR + CRh) by Initiation of Cycle 2
"The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) before initiation of Cycle 2 assessed by the investigator.~CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRh is a derived response based on bone marrow blast and hematology lab values, achieved when when the following criteria are met:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10³/μL and~Peripheral blood platelet count of > 0.5 × 10⁵/μL and~A 1-week platelet transfusion-free period prior to the hematology lab collection.~Participants with no disease assessments were considered to be non-responders." (NCT03069352)
Timeframe: Cycle 1, 28 days
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 4.4 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 30.8 |
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) and Minimal Residual Disease (MRD) Response
"The percentage of participants with complete remission or complete remission with incomplete blood count recovery AND minimal residual disease (MRD) as assessed by the investigator. Response was based on the modified IWG response criteria for AML:~CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria are met.~MRD response (at lowest-point MRD value) was defined as having less than 10-³ residual blasts per leukocyte measured in the bone marrow, per European LeukemiaNet (ELN) recommendations.~Participants who had no disease or MRD assessments were considered to be non-responders." (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 1.5 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 5.6 |
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Initiation of Cycle 2
"The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) before initiation of Cycle 2, assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML:~CR: No morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red cell transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except for RBC transfusion independence, CRi criteria are met.~Participants who had no IWG disease assessments were considered to be non-responders." (NCT03069352)
Timeframe: Cycle 1, 28 days
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 2.9 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 34.3 |
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi)
"The composite complete remission rate is defined as the percentage of participants with complete remission (CR) or complete remission with incomplete blood count recovery (CRi) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML:~CR: No morphologic evidence of AML and absolute neutrophil count (ANC) ≥ 10³/μL (1,000/μL), platelets ≥ 10⁵/μL (100,000/μL), red blood cell (RBC) transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, the CRi criteria are met.~Participants who had no IWG disease assessments were considered to be non-responders." (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 13.2 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 47.6 |
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) and Minimal Residual Disease (MRD) Response
"The percentage of participants with complete remission or complete remission with partial hematologic recovery (CRh) AND MRD response as assessed by the investigator.~CR is defined according to the modified IWG response criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRh is achieved when the following criteria are met:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10³/μL and~Peripheral blood platelet count of > 0.5 × 10⁵/μL and~A 1 week platelet transfusion-free period prior to the hematology lab collection.~MRD response (at lowest-point MRD value) was defined as less than 10-³ residual blasts per leukocyte measured in the bone marrow, per ELN recommendations.~Participants who had no disease or MRD assessments were considered to be non-responders." (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 1.5 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 5.6 |
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh)
"The percentage of participants who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) at any time point during the study assessed by the investigator.~CR is defined according to the revised guidelines by the IWG for AML as no morphologic evidence of AML, ANC count ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRh is a derived response based on bone marrow blast and hematology lab values, achieved when the following criteria are met:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10³/μL and~Peripheral blood platelet count of > 0.5 × 10⁵/μL and~A 1 week platelet transfusion-free period prior to the hematology lab collection.~Participants with no disease assessments were considered to be non-responders." (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 14.7 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 46.9 |
Percentage of Participants With Complete Remission
"The complete remission rate is defined as the percentage of participants with complete remission (CR) at any time during the study as assessed by the investigator. Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the International Working Group (IWG) for AML. CR is defined as no morphologic evidence of AML and absolute neutrophil count ≥ 10³/μL, platelets ≥ 10⁵/μL, red blood cell transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~Participants who had no IWG disease assessments were considered to be non-responders." (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 7.4 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 27.3 |
Percentage of Participants With Platelet Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
The rate of conversion was calculated as the percentage of participants who were post-baseline platelet transfusion independent among participants who had a platelet transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). Platelet transfusion independence is defined as a period of at least 56 days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier. (NCT03069352)
Timeframe: From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 12.5 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 30.2 |
Percentage of Participants With Post Baseline Platelet Transfusion Independence
The post baseline platelet transfusion independence rate was calculated as the percentage of participants who achieved platelet transfusion independence post Baseline. Platelet transfusion independence is defined as a period of at least 56 consecutive days with no platelet transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut--off date, whichever occurred earlier. (NCT03069352)
Timeframe: From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 32.4 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 47.6 |
Percentage of Participants With Post Baseline Red Blood Cell (RBC) Transfusion Independence
The post baseline red blood cell (RBC) transfusion independence rate was calculated as the percentage of participants who achieved RBC transfusion independence post baseline. RBC transfusion independence is defined as a period of at least 56 consecutive days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier. (NCT03069352)
Timeframe: From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 17.6 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 40.6 |
Percentage of Participants With RBC Transfusion Independence Among Those Who Were Transfusion Dependent at Baseline
The rate of conversion was calculated as the percentage of participants who were post-baseline RBC transfusion independent among participants who had an RBC transfusion within 8 weeks prior to the first dose of study drug (i.e. were transfusion dependent at Baseline). RBC transfusion independence is defined as a period of at least 56 days with no RBC transfusion after the first dose of study drug and on or before the last dose of study drug plus 30 days, or disease progression, or confirmed morphological relapse, or death, or the data cut-off date, whichever occurred earlier. (NCT03069352)
Timeframe: From first dose of study drug until 30 days after last dose up to the data cut-off date of 15 February 2019; Median time on treatment was 1.7 months (range: 0.1-14.2) in the placebo arm and 3.9 months (range: 0.0-17.1) in the venetoclax arm.
| Intervention | percentage of participants (Number) |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 15.1 |
| Venetoclax + Low Dose Cytarabine (LDAC) | 37.5 |
Change From Baseline in Global Health Status / Quality of Life
"The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) consists of a Global Health Status/Quality of Life (GHS/QoL) scale, a Financial Difficulties scale, 5 functional scales (Cognitive, Social, Physical, Emotional, and Role Functioning), and 8 symptom scales/items (Fatigue, Insomnia, Appetite Loss, Pain, Constipation, Diarrhea, Dyspnea, and Nausea and Vomiting).~The GHS/QoL scale includes 2 questions in which participants were asked to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The 2 scores were averaged and transformed to a scale from 0 to 100, where a high score represents a high QoL. A positive change from baseline indicates better quality of life." (NCT03069352)
Timeframe: Baseline and Day 1 of Cycles 3, 5, 7, and 9
| Intervention | scores on a scale (Least Squares Mean) |
|---|
| Cycle 3 Day 1 | Cycle 5 Day 1 | Cycle 7 Day 1 | Cycle 9 day 1 |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 1.941 | 2.627 | 3.481 | 6.918 |
,| Venetoclax + Low Dose Cytarabine (LDAC) | 4.857 | 16.015 | 10.599 | 13.299 |
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a
PROMIS Fatigue SF 7a is a seven-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always. The PROMIS Fatigue 7a score is calculated as a T-score, which is a standardized score with a mean of 50 (based on the average for the United States general population) and a standard deviation (SD) of 10. Higher scores indicate higher levels of fatigue. A decrease in score (negative change from Baseline) indicates improvement in fatigue; the minimum important difference used in this study was 3 points. (NCT03069352)
Timeframe: Baseline and Day 1 of Cycles 3, 5, 7, and 9
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Cycle 3 Day 1 | Cycle 5 Day 1 | Cycle 7 Day 1 | Cycle 9 day 1 |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 1.567 | -0.336 | -3.818 | -3.453 |
,| Venetoclax + Low Dose Cytarabine (LDAC) | -2.940 | -5.259 | -4.625 | -5.101 |
Overall Survival (OS) by Mutation Subgroups
"Overall survival is defined as the time from the date of randomization to the date of death. Participants who had not died were censored at the date they were last known to be alive on or before the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology.~Overall survival was analyzed in participants with the following molecular markers:~Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation~FMS (Feline McDonough Sarcoma)-like tyrosine kinase 3 (FLT3) mutation" (NCT03069352)
Timeframe: From randomization until the primary analysis cut-off date of February 15, 2019; the median follow-up time was 12.0 months (range: 0.2-17.0) in the placebo arm and 12.0 months (range: 0.1-17.6) in the venetoclax arm.
| Intervention | months (Median) |
|---|
| IDH1/2 mutation | FLT3 mutation |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 9.0 | 9.8 |
,| Venetoclax + Low Dose Cytarabine (LDAC) | 10.8 | 5.9 |
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR + CRi) by Mutation Subgroup
"Response was based on physical examination, bone marrow results and hematology values according to the revised guidelines by the IWG for AML:~CR: No morphologic evidence of AML and ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, and bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRi: All criteria as CR except for residual neutropenia < 10³/μL or thrombocytopenia < 10⁵/μL. If all criteria for CR are met except RBC transfusion independence, CRi criteria is met.~Participants who had no IWG disease assessments were considered to be non-responders.~Response was analyzed in participants with the following mutations:~Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation~FMS-like tyrosine kinase 3 (FLT3) mutation" (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| IDH1/2 mutation | FLT3 mutation |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 33.3 | 44.4 |
,| Venetoclax + Low Dose Cytarabine (LDAC) | 57.1 | 45.0 |
Percentage of Participants With Complete Remission or Complete Remission With Partial Hematologic Recovery (CR + CRh) by Mutation Subgroup
"The percentage of participants who achieved a complete remission or complete remission with partial hematologic recovery assessed by the investigator for participants with the following mutations:~Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutation~FMS-like tyrosine kinase 3 (FLT3) mutation~CR is defined according to the modified IWG criteria for AML as no morphologic evidence of AML, ANC ≥ 10³/μL, platelets ≥ 10⁵/μL, RBC transfusion independence, bone marrow with < 5% blasts, absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.~CRh is achieved when the following criteria are met:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count > 0.5 × 10³/μL and~Peripheral blood platelet count > 0.5 × 10⁵/μL and~A 1 week platelet transfusion-free period prior to hematology lab collection. Participants with no disease assessments were considered non-responders" (NCT03069352)
Timeframe: Response was assessed at the end of Cycle 1 and every 3 cycles thereafter to the end of treatment. Median treatment duration at the 15 February 2019 cut-off date was 1.7 months (range: 0.1-14.2) and 3.9 months (range: 0.0-17.1) in each group respectively.
| Intervention | percentage of participants (Number) |
|---|
| IDH1/2 mutation | FLT3 mutation |
|---|
| Placebo + Low Dose Cytarabine (LDAC) | 33.3 | 44.4 |
,| Venetoclax + Low Dose Cytarabine (LDAC) | 57.1 | 45.0 |
Disease-free Survival for Maintenance
DFS for maintenance comparison is defined as the time from maintenance randomization until relapse or death of any cause. The censored follow-up time for patients without relapse and death information is the date of last contact. Only patients who remained in CR or CRi after completion of consolidation therapy that were randomized to either observation or decitabine in the maintenance Step were included in this analysis. (NCT02085408)
Timeframe: Assessed every 3 months for 4 years and then every 6 months for 1 year
| Intervention | months (Median) |
|---|
| Maintenance : Observation | 8.2 |
| Maintenance : Decitabine | 16.3 |
Overall Survival by Donor Status
Overall survival is defined as time between achieving leukemia-free state after induction therapy to death from any cause or date last known alive. The association between overall survival and donor status was evaluated regardless of assigned treatment arms. Patients with transplant donor information (either had donor or did not have a donor) reported after achieving CR/Cri/leukemia-free state post induction therapy were included in this analysis. (NCT02085408)
Timeframe: Assessed every 3 months for 4 years and then every 6 months for 1 year
| Intervention | months (Median) |
|---|
| With Transplant Donor | 27.2 |
| Without Transplant Donor | 12.9 |
Overall Survival
Overall survival is defined as the time from randomization to death or date last known alive. (NCT02085408)
Timeframe: Assessed every 3 months for 4 years and then every 6 months for 1 year
| Intervention | months (Median) |
|---|
| A (Step 1:Daunorubicin/Cytarabine; Step 2:Cytarabine; Step 3: Observation/Decitabine/Transplant) | 12.9 |
| B (Step 1: Clofarabine; Step 2: Clofarabine; Step 3: Observation/Decitabine/Transplant) | 11.6 |
Proportion of Patients With Complete Remission
"Patients are required to have all of the following to be considered as having a completion remission (CR).~Peripheral Blood Counts~Neutrophil count > 1.0 x 10^9 /L~Platelet count ≥ 100 x 10^9 /L~Reduced hemoglobin concentration or hematocrit has no bearing on remission status~Leukemic blasts must not be present in the peripheral blood~Bone Marrow Aspirate and Biopsy~Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines~< 5% blasts by morphologic review~Auer rods must not be detectable~Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present" (NCT02085408)
Timeframe: Assessed every 3 months for 4 years and then every 6 months for 1 year
| Intervention | proportion of participants (Number) |
|---|
| A (Step 1:Daunorubicin/Cytarabine; Step 2:Cytarabine; Step 3: Observation/Decitabine/Transplant) | 0.446 |
| B (Step 1: Clofarabine; Step 2: Clofarabine; Step 3: Observation/Decitabine/Transplant) | 0.453 |
Complete Response Rate - Locally Reviewed
"Assessed by the ECOG-ACRIN data manager based upon local review of images and data sent by the local sites.~Treatment response was determined by calculating the sum of the maximal cross section in 2 separate axes using enhancing lesion(s) on CT or MRI imaging. The same imaging modality was to be used throughout assessment. Complete response was defined as the disappearance of all contrast enhancing tumor size on CT or MRI, patient was off all glucocorticoids, and resolution of all meningeal and vitreous involvement if present. Response must have lasted at least 4 weeks." (NCT00335140)
Timeframe: For the primary endpoint, complete response will be based on disease status at three weeks post the end of therapy (week 17).
| Intervention | percentage of participants (Number) |
|---|
| Rituximab + Standard Chemotherapy | 64 |
Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years
This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission. (NCT00176462)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Arm 2 High Risk | 64.9 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported. (NCT01190930)
Timeframe: 1.7 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.80 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.89 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported. (NCT01190930)
Timeframe: 1.7 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.62 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.64 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported. (NCT01190930)
Timeframe: 1.7 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.16 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.25 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.72 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.77 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.64 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.67 |
Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.27 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.34 |
Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2 Months
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -1.21 |
Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Physical
Age and gender standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2 Months
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -1.44 |
Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2 Months
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.42 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1 year
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.86 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1 Year
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.59 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1 Year
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.19 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1.7 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.84 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1.7 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.63 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 1.7 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.20 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.5 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.74 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.66 |
Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.30 |
Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.71 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.51 |
Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.85 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.47 |
Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Social Functioning
Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -0.46 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.33 |
Burden of Therapy in Boy AR Patients Overall at End of Therapy: Emotional
Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Genetic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.62 |
Burden of Therapy in Boy AR Patients Overall at End of Therapy: Physical
Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.67 |
Burden of Therapy in Boy AR Patients Overall at End of Therapy: Social Functioning
Age standardized Quality of life, measured by the Social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported. (NCT01190930)
Timeframe: 3.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.40 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Left
Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 4.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -1.19 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Right
Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 4.2 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -1.12 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Left
Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 2 Months
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.84 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Right
Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 2 Months
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.87 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Left
Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 1 Year
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.36 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Right
Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 1 Year
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.39 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left
Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.28 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right
Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk | -0.27 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left
Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -1.19 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | 0.21 |
Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right
Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported. (NCT01190930)
Timeframe: 2.4 Years
| Intervention | Z-Score (Mean) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | -1.12 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | -0.02 |
DFS for SR Down Syndrome Patients With Standardized Treatment and Enhanced Supportive Care
DFS is calculated as the time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. The 5-year DFS and 95% confidence interval for these patients will be estimated. (NCT01190930)
Timeframe: 5.1 years
| Intervention | percent probability (Number) |
|---|
| Standard Risk With Down Syndrome | 89.77 |
DFS in Average Risk (AR) Patients Based on the Pulse Frequency Randomization
DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated. (NCT01190930)
Timeframe: 5.7 years
| Intervention | percent probability (Number) |
|---|
| B-ALL Average Risk: VCR/DEX Pulse Every 4 Weeks | 94.10 |
| B-ALL Average Risk: VCR/DEX Pulse Every 12 Weeks | 95.13 |
DFS in Low Risk (LR) Patients Based on Randomization to 1 of 2 Low-intensity Regimens
DFS is calculated as the time from randomization at the end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated. (NCT01190930)
Timeframe: 5.1 years
| Intervention | percent probability (Number) |
|---|
| B-ALL Low Risk Arm I (LR-M) | 98.75 |
| B-ALL Low Risk Arm II (LR-C) | 98.50 |
Disease Free Survival (DFS) in Average Risk (AR) Patients Based on the Methotrexate Dose Randomization
DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated. (NCT01190930)
Timeframe: 5.7 years
| Intervention | percent probability (Number) |
|---|
| B-ALL Average Risk: MTX 20 mg/m^2/Week Starting Dose | 95.05 |
| B-ALL Average Risk: MTX 40 mg/m^2/Week Starting Dose | 94.17 |
Event Free Survival (EFS) for B-LLy Patients
EFS is calculated as the Time from study enrollment to first event (induction failure, relapse, second malignancy, remission death) or date of last contact. The 5-year EFS and 95% confidence interval for these patients will be estimated. (NCT01190930)
Timeframe: 5 years
| Intervention | percent probability (Number) |
|---|
| B-LLy | 94.54 |
Overall Survival (OS) for B-LLy Patients
OS is calculated as the time from study enrollment to death or date of last contact. The 5-year OS and 95% confidence interval for these patients will be estimated. (NCT01190930)
Timeframe: 5 years
| Intervention | percent probability (Number) |
|---|
| B-LLy | 93.97 |
Sample Collection of Central Path Review Slides in B-LLy Patients
Percent of B-LLy patients who had adequate/usable samples of samples collected will be reported. (NCT01190930)
Timeframe: Up to 1 month
| Intervention | percentage of patients (Number) |
|---|
| B-LLy | 89.7 |
Blast Response
Blast response was defined as a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days. (NCT01056523)
Timeframe: 2-3 years
| Intervention | Participants (Count of Participants) |
|---|
| Ribavirin and Cytarabine | 2 |
Complete Response Rate
Defined as <5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL. (NCT01056523)
Timeframe: 2-3 years
| Intervention | Participants (Count of Participants) |
|---|
| Ribavirin and Cytarabine | 2 |
Overall Response Rate
Overall response rate comprises complete response (<5% blasts in the bone marrow, and in the peripheral blood Hgb more than or equal to 100 g/L, platelets more than or equal to 100x10-9/L, and neutrophils more than or equal to 1x10-9/L), partial response (5 to 25% blasts in the bone marrow and same peripheral blood parameters) and blast response (a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days). (NCT01056523)
Timeframe: 2-3 years
| Intervention | Participants (Count of Participants) |
|---|
| Ribavirin and Cytarabine | 5 |
Partial Response
Partial response was defined as 5 to 25% blasts in the bone marrow and Hgb >100g/L, platelets >100,000/ul and neutrophils >1000/ul. (NCT01056523)
Timeframe: 2-3 years
| Intervention | Participants (Count of Participants) |
|---|
| Ribavirin and Cytarabine | 1 |
Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C
This 3+3 designed aimed to determine recommended phase II dose (RP2D) based on pharmacokinetics (PK) and maximum tolerated dose (MTD). For the dose to be selected, a target steady state level of ribavirin 20 uM was needed for all patients and no more than 1 of 6 patients could have had dose limiting toxicity at that dose. (NCT01056523)
Timeframe: 56 days
| Intervention | mg (Number) |
|---|
| Ribavirin po bid for 28 days | cytarabine arabinoside sc bid for 10 days |
|---|
| Ribavirin-Cytarabine | 1400 | 10 |
AALL08P1 Feasibility Outcome
Percentage of Group B (High Risk-High) patients that tolerate at least 8 of the 12-14 total doses of pegaspargase during Consolidation, Interim Maintenance, and Delayed Intensification periods. Only Grp B analyzed since this is prespecified in protocol. (NCT00866307)
Timeframe: Consolidation through Delayed Intensification
| Intervention | percentage of participants (Number) |
|---|
| Group B (High Risk-High) | 53.3 |
AALL08P1 Safety Outcome
Percentage of Group B (High Risk-High) patients taking less than 49 weeks from day 1 of consolidation to day 1 of maintenance therapy. Only Group B analyzed since this is prespecified in protocol. (NCT00866307)
Timeframe: Consolidation through Delayed Intensification
| Intervention | percentage of participants (Number) |
|---|
| Group B (High Risk-High) | 50.0 |
Participant Progression Free Survival at 2 Years
Progression-free survival defined as the number of participants without evidence of progression or death after 2 years from stem cell transplant. (NCT00505921)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Campath-1H | 15 |
Median Time to Disease Progression
median days from transplant to relapse/progression (NCT00992446)
Timeframe: time post ASCT to progression
| Intervention | years (Median) |
|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | 1.05 |
Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant
Number of patients on maintenance therapy post-transplant who experienced grade 3 or higher toxicity per NCI-Common Terminology Criteria for Adverse Events, version 3. The first three months of bortezomib and vorinostat therapy will be used as the time period to evaluate toxicity for stopping rules of the study. Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy). (NCT00992446)
Timeframe: 3 months after start of maintenance therapy
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | 19 |
Event-free Survival
Number of patients alive without disease progression/relapse (NCT00992446)
Timeframe: 6.64 Years Post-Transplant
| Intervention | Participants (Count of Participants) |
|---|
| Alive without disease porgression | alive with disease progression |
|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | 14 | 5 |
Overall Survival
Number of patients alive who received maintenance therapy (NCT00992446)
Timeframe: 6.64 Years Post-Transplant
| Intervention | participants (Number) |
|---|
| Alive | Dead |
|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | 16 | 3 |
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity
(NCT00906945)
Timeframe: 6 hours after plerixafor
| Intervention | fold change in CXCR4 clone 1D9 (Mean) |
|---|
| Phase I and Phase II Participants | 0.9 |
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity
(NCT00906945)
Timeframe: 6 hours after plerixafor
| Intervention | fold change in CXCR4 clone 1D9 (Mean) |
|---|
| Phase I and Phase II Participants | 8.0 |
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count
(NCT00906945)
Timeframe: 6 hours after plerixafor
| Intervention | fold change in AML blast count (Mean) |
|---|
| Phase I and Phase II Participants | 9.4 |
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells
(NCT00906945)
Timeframe: 6 hours after plerixafor
| Intervention | fold change in white blood cells (Mean) |
|---|
| Phase I and Phase II Participants | 4.6 |
Overall Survival
Overall survival: Defined as the date of first dose of study drug to the date of death from any cause. (NCT00906945)
Timeframe: Median follow-up was 34.6 months
| Intervention | days (Median) |
|---|
| Phase I and Phase II Participants | 227 |
Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC
(NCT00906945)
Timeframe: Completion of Phase I enrollment (17 months)
| Intervention | mcg/kg/day (Number) |
|---|
| Phase I (Includes Levels 1-5) | 750 |
Phase II: Complete Response Rate (CR+CRi)
"Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1,000/mm3, platelet count > 100,000/mm3.~Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1,000/mm3 or thrombocytopenia <100,000/mm3." (NCT00906945)
Timeframe: 45 days
| Intervention | percentage of participants (Number) |
|---|
| Phase II (MTD) | 30 |
Relapse Free-survival Rate
(NCT00906945)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Phase I and Phase II Participants | 75 |
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
-Neutrophil recovery is defined as absolute neutrophil count (ANC) >= 500/mm^3 (NCT00906945)
Timeframe: Up to 62 days after treatment
| Intervention | days (Median) |
|---|
| Phase I and Phase II Participants | 38 |
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
-Neutrophil recovery is defined as absolute neutrophil count >= 1000/mm^3 (NCT00906945)
Timeframe: Up to 62 days after treatment
| Intervention | days (Median) |
|---|
| Phase I and Phase II Participants | 40 |
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
-Platelet recovery is defined as platelets >= 100,000/mm3 (NCT00906945)
Timeframe: Up to 62 days after treatment
| Intervention | days (Median) |
|---|
| Phase I and Phase II Participants | 32 |
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
-Platelet recovery is defined as platelets >= 50,000/mm^3 (NCT00906945)
Timeframe: Up to 62 days after treatment
| Intervention | days (Median) |
|---|
| Phase I and Phase II Participants | 32 |
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
(NCT00906945)
Timeframe: 30 days following end of treatment
| Intervention | number of events (Number) |
|---|
| Anemia | Febrile neutropenia | Abdominal pain | Constipation | Diarrhea | Gastroesophageal reflux disease | Mucositis oral | Nausea | Vomiting | Chills | Edema-limbs | Fatigue | Fever | Non-cardiac chest pain | Pain | Bacteremia | Lung infection | Sepsis | Activated partial thromboplastin time prolonged | Alanine aminotransferase increased | Alkaline phosphatase increased | Aspartate aminotransferase increased | Blood bilirubin increased | INR increased | Neutrophil count decreased | Platelet count decreased | White blood cell count decreased | Anorexia | Hypoalbuminemia | Hypocalcemia | Hypokalemia | Hypomagnesemia | Hyponatremia | Bone pain | Dizziness | Headache | Paresthesia | Insomnia | Proteinuria | Cough | Dyspnea | Pneumonitis | Rash maculo-papular | Hypotension |
|---|
| Grade 1 | 0 | 0 | 6 | 5 | 7 | 1 | 2 | 21 | 12 | 5 | 5 | 9 | 6 | 1 | 2 | 0 | 0 | 0 | 5 | 3 | 3 | 4 | 2 | 7 | 0 | 0 | 0 | 4 | 3 | 2 | 5 | 7 | 4 | 4 | 4 | 7 | 4 | 5 | 3 | 3 | 3 | 1 | 3 | 4 |
,| Grade 2 | 4 | 0 | 0 | 2 | 6 | 5 | 3 | 3 | 0 | 0 | 1 | 2 | 4 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 2 | 6 | 11 | 2 | 0 | 0 | 2 | 1 | 6 | 1 | 2 | 1 | 2 | 3 | 3 | 3 | 4 |
,| Grade 3 | 9 | 20 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 4 | 5 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
,| Grade 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 15 | 16 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Grade 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Number of Participants Who Experienced Dose Limiting Toxicities (DLT)
Dose-limiting toxicities were defined as events related to onvansertib that were considered an adverse reaction or suspected adverse reaction during the first cycle of therapy and that fulfilled one of the following: Hematologic (persistent pancytopenia resistant to current standards of care that continues for ≥42 days and is not related to leukemic infiltration or another cause unrelated to study therapy) or Non-Hematologic (any Grade 3 abnormalities that persist >7 days without decreasing in severity despite standards of care, are clinically significant, or that are Grade 4 and symptomatic). (NCT03303339)
Timeframe: Up to Day 28 of Cycle 1
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 0 |
| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 0 |
| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 0 |
| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 0 |
| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 0 |
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 0 |
| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 0 |
| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 0 |
| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 0 |
| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 0 |
| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 2 |
Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
ECOG performance status was determined using 6-point scale from 0-5, with 0 meaning a participant was fully active/able to carry on all pre-disease activities without restriction and 5 meaning the participant was deceased. (NCT03303339)
Timeframe: Baseline and end of study (approximately up to up to 27 months)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1b: Onvansertib + Low-dose Cytarabine | 11 |
| Phase 1b: Onvansertib + Decitabine | 14 |
| Phase 2: Onvansertib + Decitabine | 22 |
Phase 2: Duration of Response (DOR)
Duration of Response (DOR) is the time (in months) from the first response of CR, CRi or PR until recurrence of or progression of disease (or death). MLF State is also included as a response when calculating DOR. Responding subjects without death or progression will be censored at the date of their last evaluable disease assessment. (NCT03303339)
Timeframe: Up to 27 months
| Intervention | months (Median) |
|---|
| Phase 2: Onvansertib + Decitabine | 5.2 |
Phase 2: Event-free Survival (EFS)
EFS is defined as the time from enrollment until disease progression or death from any cause and reported as the proportion of participants event free at 12 months. (NCT03303339)
Timeframe: 12 Months
| Intervention | Proportion of Participants (Number) |
|---|
| Phase 2: Onvansertib + Decitabine | 0.1 |
Phase 2: Number of Participants Who Achieved a Complete Response (CR)
"Complete Response also includes Complete Response with Incomplete Blood Count Recovery (CRi). Complete response is defined by the following criteria:~Morphologic leukemia-free state plus:~Subject is independent of transfusions~Absolute neutrophil count of >1000/mm3~Platelets of ≥100,000/mm3~Complete response with incomplete blood count recovery meets all criteria for CR except for either neutropenia (ANC <1000/mm3) or thrombocytopenia (<100,000/mm3) but must include transfusion independence." (NCT03303339)
Timeframe: Up to 27 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2: Onvansertib + Decitabine | 3 |
Phase 2: Number of Participants Who Achieved a Morphologic Leukemia-free (MLF) State
Defined as bone marrow (BM) <5% blasts in an aspirate with spicules and no blasts with Auer rods or persistence of extramedullary disease. (NCT03303339)
Timeframe: Up to 27 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2: Onvansertib + Decitabine | 1 |
Phase 2: Number of Participants With Partial Response (PR)
PR criteria includes all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate and a normalization of blood counts. (NCT03303339)
Timeframe: Up to 27 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2: Onvansertib + Decitabine | 0 |
Phase 2: Overall Survival (OS)
OS is defined as the time from enrollment until death from any cause and reported as the proportion of participants alive at 12 months. (NCT03303339)
Timeframe: 12 Months
| Intervention | Proportion of Participants (Number) |
|---|
| Phase 2: Onvansertib + Decitabine | 0.2 |
Number of Participants With Adverse Events (AEs)
Any clinically significant change in electrocardiogram (ECG), physical examination findings, body weight, vital signs, and laboratory parameters were recorded as Adverse Events. (NCT03303339)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 27 months)
| Intervention | Participants (Count of Participants) |
|---|
| Any Adverse Events | Any Serious Adverse Events | Any Treatment-Related Serious Adverse Events |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 4 | 2 | 0 |
,| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 3 | 2 | 0 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 3 | 3 | 0 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 3 | 3 | 1 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 3 | 3 | 1 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 3 | 1 | 0 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 4 | 4 | 0 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 3 | 2 | 1 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 3 | 2 | 1 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 5 | 3 | 0 |
,| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 6 | 5 | 3 |
,| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | 32 | 27 | 5 |
Pharmacokinetic Parameter: Area Under the Curve Over the First 24 Hours AUC(0-24) for Onvansertib
(NCT03303339)
Timeframe: Cycle 1: Days 1 and 5
| Intervention | h*ng/mL (Geometric Least Squares Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5 |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 1099.43 | 1868.69 |
,| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 1197.93 | 1868.69 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 2789.81 | 3626.44 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 772.68 | 3626.44 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 3257.57 | 5343.01 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 2534.22 | 5343.01 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 4084.18 | 7415.04 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 2761.11 | 7415.04 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 9599.19 | 19470.17 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 5386.69 | 19470.17 |
,| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 9087.77 | 12981.17 |
,| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | 6280.28 | 11767.29 |
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) for Onvansertib
(NCT03303339)
Timeframe: Cycle 1: Days 1 and 5
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5 |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 80.15 | 146.10 |
,| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 92.57 | 139.22 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 129.18 | 197.67 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 69.56 | 103.27 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 309.86 | 398.38 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 251.16 | 298.63 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 410.42 | 496.24 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 256.11 | 339.52 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 724.76 | 955.59 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 626.18 | 857.29 |
,| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 737.21 | 1137.16 |
,| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | 515.63 | 861.86 |
Pharmacokinetic Parameter: Plasma Terminal Elimination Half-life (t1/2) for Onvansertib
(NCT03303339)
Timeframe: Cycle 1: Days 1 and 5
| Intervention | Hours (Geometric Least Squares Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5 |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 16.960 | 13.282 |
,| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 11.294 | 16.413 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 13.795 | 9.082 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 7.993 | 12.561 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 9.394 | 10.713 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 12.197 | 12.246 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 11.389 | 16.337 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 11.747 | 7.321 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 12.917 | 44.018 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 7.309 | 14.484 |
,| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 12.633 | 12.378 |
,| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | 11.904 | 14.060 |
Pharmacokinetic Parameter: Time to Reach the Maximum Observed Plasma Concentration (Tmax) for Onvansertib
(NCT03303339)
Timeframe: Cycle 1: Days 1 and 5
| Intervention | Hours (Geometric Least Squares Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5 |
|---|
| Phase 1b: Onvansertib 12 mg/m^2 + Decitabine | 3.102 | 2.438 |
,| Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine | 1.961 | 1.844 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Decitabine | 2.365 | 1.583 |
,| Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine | 2.548 | 2.892 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Decitabine | 1.288 | 3.145 |
,| Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine | 2.301 | 2.267 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Decitabine | 1.373 | 3.161 |
,| Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine | 1.384 | 1.474 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Decitabine | 2.893 | 3.161 |
,| Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine | 2.071 | 2.148 |
,| Phase 1b: Onvansertib 90 mg/m^2 + Decitabine | 2.435 | 3.189 |
,| Phase 2: Onvansertib 60 mg/m^2 + Decitabine | 2.725 | 2.665 |
Median of Serum Complement CD20 Levels
Median serum C20 MFI (mean fluorescence intensity) (NCT01527149)
Timeframe: Baseline
| Intervention | mean fluorescence intensity (Median) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 186.8 |
Median Overall Survival (OS)
Estimated distributions obtained using the Kaplan-Meier method. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. (NCT01527149)
Timeframe: From baseline through study completion, an average of 5 years
| Intervention | months (Median) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 56.0 |
Median Progression-free Survival (PFS)
Estimated distributions obtained using the Kaplan-Meier method. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. (NCT01527149)
Timeframe: From baseline through study completion, an average of 5 years
| Intervention | months (Median) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 45.5 |
Number of Participants With at Least One Serious Adverse Event
Evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. (NCT01527149)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 19 |
Percentage of Participants With Autologous Stem Cell Transplantation
Estimated using simple relative frequencies. The corresponding 95% confidence intervals will be computed using the method proposed in Clopper and Pearson. (NCT01527149)
Timeframe: Up to 6 weeks after the last dose of ofatumumab-chemotherapy, an average of 4 month
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 73 |
Proportion of Patients Experiencing a Complete Response
"Evaluated according to the International Working Group Response criteria as reported by Cheson et al. and the revised Cheson criteria.~Complete response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Typically FDG-avid lymphoma: in patients with PET scan positive before therapy, a posttreatment residual mass of any size is permitted as long as it is PET negative. Variably FDG-avid lymphomas/FDG avidity unknown: in patients with a negative pretreatment PET scan, all lymph nodes and nodal masses must have regressed on CT to normal size (1.5 cm in their greatest transverse diameter for nodes 1.5 cm before therapy). Previously involved nodes that were 1.1 cm to 1.5 cm in their long axis and more than 1)" (NCT01527149)
Timeframe: 22 weeks
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | .62 |
Proportion of Patients Who Experience Complete Remission as Assessed by HSFCM
Established when all CR criteria are met and negative flow cytometry examination of peripheral blood and bone marrow biopsy/aspiration collected at baseline, before courses 3 and 5, within 3 weeks after course 6, on day 100 (if HDC-ASCT eligible), and then every 6 months for 3 years. (NCT01527149)
Timeframe: Up to 3 years
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | .84 |
Time-to-tumor Progression (TTP) at 3 Years
Estimated percentage of patients that progressed at 3 years. Time to Progression distributions obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. (NCT01527149)
Timeframe: From baseline until objective tumor progression, as assessed up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | 76 |
Change From Baseline in Percentage of Cells Positive for Ki67
Mean change from baseline in Percentage of Cells Positive for Ki67 by patient response. (NCT01527149)
Timeframe: Baseline and up to 3 years
| Intervention | percentage of cells positive for Ki-67 (Mean) |
|---|
| Not CR | CR |
|---|
| Treatment (Monoclonal Antibody and Combination Chemotherapy) | -2.5 | NA |
Number of Biomarker-positive Participants With Clinical Responses
"Biomarkers: FLT3-ITD positive, NPM1 positive, CEBPA. A good CR is defined as <5% blasts in the marrow by morphologic evaluation along with the absence of any MRD by flow cytometry or cytogenetics and recovery of blood counts (platelets >100,00 and absolute neutrophil count >1,000) by day 35 after induction. Cheson AML Response Criteria is used for Morphologic Leukemia Free State, Morphologic Complete Remission, Cytogenetic Complete Remission (CRc), Molecular Complete Remission (CRm), Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR), Treatment Failure, Recurrence (Progressive Disease)." (NCT01831232)
Timeframe: 38 days after dosing
| Intervention | participants with clinical responses (Number) |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 0 |
Number of Participants With Good Complete Remission (CR)
"A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used.~Definition of Good CR: Conventional criteria for CR (absolute neutrophil count > 1,000/uL, platelet count > 100,000/uL, marrow with <5% morphologic blasts) and additionally the requirements that marrow Minimal Residual Disease (MRD) - detected by 10-color flow cytometry or conventional cytogenetic evaluation - be absent and that the above blood counts be obtained." (NCT01831232)
Timeframe: 35 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 12 |
Number of Participants With TRM.
"A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used.~TRM: Treatment Related Mortality" (NCT01831232)
Timeframe: 28 days
| Intervention | participants (Number) |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 2 |
Overall Survival
Amount of time a patient lives after treatment with IAP (NCT01831232)
Timeframe: 1 year after treatment with IAP
| Intervention | percentage of patients surviving (Number) |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 53.5 |
Progression Free Survival (PFS)
(NCT01831232)
Timeframe: 1 year after treatment with IAP
| Intervention | percentage of patients with PFS (Number) |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 52.6 |
Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR)
Complete remission (CR) - includes patients with good CR and CR with minimal residual disease (MRD); remission with incomplete blood count recovery (CRi), partial remission (PR) (NCT01831232)
Timeframe: 35 days
| Intervention | Participants (Count of Participants) |
|---|
| CR | CRi | PR |
|---|
| Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) | 15 | 2 | 0 |
Disease-free Survival in Patients Undergoing Autologous Stem Cell Transplant
(NCT00774046)
Timeframe: Up to 883 days
| Intervention | Days (Median) |
|---|
| All Patients | 367 |
Feasibility of Stem Cell Collection
Feasibility is the ability to cryopreserve >=2.0 x 10^6 CD34+ cells/kg (NCT00774046)
Timeframe: 1-5 days from initiation of stem cell collection
| Intervention | percentage of participants (Number) |
|---|
| All Patients | 70 |
Numbers of Stem Cells Collected
(NCT00774046)
Timeframe: 1-5 days from initiation of stem cell collection
| Intervention | 10^6 CD34+ cells/kg (Median) |
|---|
| All Patients | 4.50 |
Overall Survival in Patients Undergoing Autologous Stem Cell Transplant
(NCT00774046)
Timeframe: Up to 817 days
| Intervention | Days (Median) |
|---|
| All Patients | 294 |
Overall Survival
(NCT00774046)
Timeframe: Up to 2000 days
| Intervention | Days (Median) |
|---|
| All Patients | 399 |
Relapse-free Survival
Relapse is defined as bone marrow blasts >5% if the patient had achieved a complete remission, or the recurrence of any clonal cytogenetic abnormality. (NCT00774046)
Timeframe: Up to 2000 days
| Intervention | Days (Median) |
|---|
| All Patients | 415 |
Response to Induction Chemotherapy (CR or PR)
Complete remission (CR): <5% bone marrow blasts with recovery of peripheral blood counts; complete cytogenetic remission, the disappearance of any pre-existing cytogenetic abnormality Partial remission (PR): >5% bone marrow blasts, but less than the pre-treatment blast percentage within the bone marrow Resistant disease (RD): no significant cytoreduction in bone marrow leukemic cells from pre-treatment levels Not evaluable (NE): patients who died during induction chemotherapy or who withdrew from follow-up before assessment could be made (NCT00774046)
Timeframe: Day 28-40
| Intervention | percentage of participants (Number) |
|---|
| All Patients | 81.2 |
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
To evaluate the side effects of giving Azacytidine before and during chemotherapy using the standard drugs Fludarabine, Cytarabine, IT Cytarabine (AML patients) and IT methotrexate (ALL patients) (NCT01861002)
Timeframe: From Day 1 to Day 42 (Cycle 1)
| Intervention | Participants (Count of Participants) |
|---|
| # of patients with DLT | # of patients without DLT | # of patients not evaluable |
|---|
| Dose 75 mg/m2/Day Azacytidine Diagnosed With ALL | 0 | 2 | 0 |
,| Dose 75 mg/m2/Day Azacytidine Diagnosed With AML | 0 | 12 | 1 |
5-Year Disease-Free Survival by Bone Marrow Day 18 Status
Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI. (NCT00400946)
Timeframe: Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.
| Intervention | probability (Number) |
|---|
| M1 Day 18 Bone Marrow Status | .89 |
| M2/M3 Day 18 Bone Marrow Status | .78 |
| Hypocellular Day 18 Bone Marrow Status | .88 |
5-year Disease-Free Survival by CNS Directed Treatment Group
Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI. (NCT00400946)
Timeframe: Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.
| Intervention | probability (Number) |
|---|
| CNS-1 | .89 |
| CNS-2 | .89 |
| CNS-3 | 1.00 |
| Traumatic Tap With Blasts | .84 |
| Traumatic Tap Without Blasts | .87 |
5-Year Disease-Free Survival by MRD Day 32 Status
Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI. (NCT00400946)
Timeframe: Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.
| Intervention | probability (Number) |
|---|
| Low Day 32 MRD Level | .79 |
| High Day 32 MRD Level | .90 |
5-Year Disease-Free Survival
Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI. (NCT00400946)
Timeframe: Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.
| Intervention | probability (Number) |
|---|
| Intramuscular Native E Coli L-asparaginase (IM-EC) | .89 |
| Intravenous PEG-asparaginase (IV-PEG) | .90 |
Asparaginase-Related Toxicity Rate
Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), symptomatic pancreatitis (grade 2 or worse), thrombotic or bleeding complications requiring intervention (grade 2 or worse) with treatment attribution of possibly, probably or definite based on CTCAEv3. (NCT00400946)
Timeframe: 30-week post-induction asparaginase treatment period
| Intervention | percentage of participants (Number) |
|---|
| Intramuscular Native E Coli L-asparaginase (IM-EC) | 26 |
| Intravenous PEG-asparaginase (IV-PEG) | 28 |
Induction Infection Toxicity Rate
Infection toxicity rate is defined as the percentage of patients who experience bacterial or fungal infection of grade 3 or higher with treatment attribution of possibly, probably or definite based on CTCAEv3 during remission induction phase of combination chemotherapy. (NCT00400946)
Timeframe: Assessed daily during remission induction days 4-32.
| Intervention | percentage of participants (Number) |
|---|
| Overall | 26 |
Post-Induction Therapeutic Nadir Serum Asparaginase Activity Rate
Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. Post-Induction therapeutic NSAA rate is defined as the percentage of patients achieving a NSAA level above 0.1 IU/mL ever during post-induction therapy. (NCT00400946)
Timeframe: Samples for nadir serum asparaginase activity analyses were obtained before doses administered at weeks 5, 11, 17, 23 and 29 of post-induction asparaginase treatment.
| Intervention | percentage of participants (Number) |
|---|
| Intramuscular Native E Coli L-asparaginase (IM-EC) | 71 |
| Intravenous PEG-asparaginase (IV-PEG) | 99 |
Induction Serum Asparaginase Activity Level
Serum asparaginase activity (NSAA) levels were estimated based on established methods. (NCT00400946)
Timeframe: Samples for serum asparaginase activity analyses were obtained days 4, 11, 18 and 25 post one-dose of IV-PEG on day 7 of the induction phase.
| Intervention | IU/mL (Median) |
|---|
| Day 4 NSAA Level | Day 11 NSAA Level | Day 18 NSAA Level | Day 25 NSAA Level |
|---|
| Overall | .694 | .505 | .211 | .048 |
Induction Therapeutic Nadir Serum Asparaginase Activity Rate
Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. Induction therapeutic NSAA rate is defined as the percentage of patients achieving a NSAA level above 0.1 IU/mL at a given timepoint. (NCT00400946)
Timeframe: Samples for serum asparaginase activity analyses were obtained days 4, 11, 18 and 25 post one-dose of IV-PEG on day 7 of the induction phase.
| Intervention | percentage of participants (Number) |
|---|
| Day 4 NSAA Rate | Day 11 NSAA Rate | Day 18 NSAA Rate | Day 25 NSAA Rate |
|---|
| Overall | 97 | 96 | 87 | 12 |
Post-Induction Nadir Serum Asparaginase Activity Level
Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. (NCT00400946)
Timeframe: Samples for nadir serum asparaginase activity analyses were obtained before doses administered at weeks 5, 11, 17, 23 and 29 of post-induction asparaginase treatment.
| Intervention | IU/mL (Mean) |
|---|
| Week 5 NSAA Level | Week 11 NSAA Level | Week 17 NSAA Level | Week 23 NSAA Level | Week 29 NSAA Level |
|---|
| Intramuscular Native E Coli L-asparaginase (IM-EC) | 0.129 | 0.143 | 0.159 | 0.180 | 0.123 |
,| Intravenous PEG-asparaginase (IV-PEG) | 0.726 | 0.773 | 0.787 | 0.757 | 0.806 |
Event-Free Survival
Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse. (NCT03488225)
Timeframe: Start of treatment up to 2 years
| Intervention | Months (Median) |
|---|
| Treatment (Hyper-CVAD, Inotuzumab Ozogamicin) | 24 |
Number of Participants With Minimal Residual Disease (MRD) Negativity
MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle. (NCT03488225)
Timeframe: Start of treatment up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Hyper-CVAD, Inotuzumab Ozogamicin) | 4 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT03488225)
Timeframe: Start of treatment up to 2 years
| Intervention | Months (Median) |
|---|
| Treatment (Hyper-CVAD, Inotuzumab Ozogamicin) | 24 |
Participants to Achieve Complete Remission (CR):
Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts /= 100X10^9/L and complete resolution of all sites of extramedullary disease. (NCT03488225)
Timeframe: Start of treatment up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Hyper-CVAD, Inotuzumab Ozogamicin) | 4 |
Number of Participants With Adverse Events
For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting. (NCT03488225)
Timeframe: Start of treatment up to 30 days after last dose received.
| Intervention | Participants (Count of Participants) |
|---|
| Neutropenic Fever | Peripheral Sensory Neuropathy | Allergic Reaction | Muscle Weakness |
|---|
| Treatment (Hyper-CVAD, Inotuzumab Ozogamicin) | 2 | 1 | 1 | 1 |
Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to First Course of Azacitidine
Will calculate the percentage of CpG site methylation for all patients before the first course of azacitidine. Mean and standard deviation will be reported. (NCT02828358)
Timeframe: Week 6, Day 1 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy)
| Intervention | Percentage of CpG methylation (Mean) |
|---|
| KMT2A-Rearranged | 78.17 |
Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to Second Course of Azacitidine
Will calculate the percentage of CpG site methylation for all patients before the second course of azacitidine. Mean and standard deviation will be reported. (NCT02828358)
Timeframe: Week 13, Day 1 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy)
| Intervention | Percentage of CpG methylation (Mean) |
|---|
| KMT2A-Rearranged | 76.5 |
Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of First Course of Azacitidine
Will calculate the percentage of CpG site methylation for all patients after the first course of azacitidine. Mean and standard deviation will be reported. (NCT02828358)
Timeframe: Week 6, Day 5 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy)
| Intervention | Percentage of CpG methylation (Mean) |
|---|
| KMT2A-Rearranged | 75.54 |
Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of Second Course of Azacitidine
Will calculate the percentage of CpG site methylation for all patients after the second course of azacitidine. Mean and standard deviation will be reported. (NCT02828358)
Timeframe: Week 13, Day 5 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy)
| Intervention | Percentage of CpG methylation (Mean) |
|---|
| KMT2A-Rearranged | 74.52 |
Tolerability of Azacitidine in Combination With Interfant-06 Standard Chemotherapy in Evaluable Infant Patients With Newly Diagnosed ALL With KMT2A Gene Rearrangement (KMT2A-R). KMT2A Gene Rearrangement (KMT2A-R)
Proportion of KMT2A-Rearranged patients treated with azacitidine with Dose Limiting Toxicities (DLTs) from the first course of azacitidine administration up to fourth course of azacitidine administration. (NCT02828358)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| KMT2A-Rearranged | 6.45 |
Number of Participants Who Experienced Dose-limiting Toxicity (DLT)
Defined as induction mortality (death occurring on or before day 60), grade 3 or 4 non-hematologic toxicity, or dose limiting hematologic toxicity at least possibly related to the study drug occurring during the first 28 days from the start of therapy. Estimated for each arm with 95% confidence intervals. Fisher's exact test will be used to compare the toxicity rate between the two dose levels. (NCT02286726)
Timeframe: Up to day 60
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lower-dose (50 Units/m^2) CPX-351) | 5 |
| Arm II (Intermediate-dose (75 Units/m^2) CPX-351) | 3 |
| Arm III (Standard-dose (100 Units/m^2) CPX-351) | 3 |
Number of Participants With a Response
Response is defined as Complete response (CR) or CR with incomplete blood count recovery (CRi) rate: Complete Remission (CR) is Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 10^9/L (1000/μL); platelet count >100 x 10^9/L (100,000/μL). Complete Response with incomplete blood count recovery (CRi) is All CR criteria except for residual neutropenia (<1.0 x 10^9/L [1000/μL]) and/or thrombocytopenia (<100 x 10^9/L [100,000/μL]). (NCT02286726)
Timeframe: Up to 8 weeks (after induction therapy)
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Complete Response with incomplete blood count recovery (CRi) |
|---|
| Arm I (Lower-dose (50 Units/m^2) CPX-351) | 3 | 0 |
,| Arm II (Intermediate-dose (75 Units/m^2) CPX-351) | 6 | 3 |
,| Arm III (Standard-dose (100 Units/m^2) CPX-351) | 7 | 0 |
Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
Described via means and standard deviations in available Arm C relapse samples (NCT00557193)
Timeframe: At relapse (up to 3 years)
| Intervention | qPCR fold expression ratio (Mean) |
|---|
| Arm C (Safety/Efficacy Dose Level 2) | 5.73 |
Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
Described via mean and standard deviation by group. (NCT00557193)
Timeframe: Sampled at the start of induction
| Intervention | qPCR fold expression ratio (Mean) |
|---|
| Arm A (Standard Risk MLL-G) | 1.25 |
| Arm B (IR/HR MLL-R Chemotherapy) | 7.85 |
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) | 5.83 |
Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts
Described via means and standard deviations in samples which have acquired resistance to lestaurtinib (NCT00557193)
Timeframe: At relapse (up to 3 years)
| Intervention | Proportion of cells that are viable (Mean) |
|---|
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) | 0.69 |
Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts
Described via means and standard deviations in samples which have primary resistance to lestaurtinib (NCT00557193)
Timeframe: Sampled at the start of induction
| Intervention | Proportion of cells that are viable (Median) |
|---|
| Arm A (Standard Risk MLL-G) | 0.75 |
| Arm B (IR/HR MLL-R Chemotherapy) | 0.48 |
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) | 0.47 |
Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT)
Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients. (NCT00557193)
Timeframe: Up to 12 weeks from start of induction
| Intervention | Participants (Count of Participants) |
|---|
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 1) | 0 |
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib-Dose Level 2) | 1 |
Percent Probability for Event-free Survival (EFS) for Patients on Arm A
EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. (NCT00557193)
Timeframe: From start of post-induction therapy for up to 10 years
| Intervention | percentage probability (Number) |
|---|
| Arm A (Standard Risk MLL-G) | 86.67 |
Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2)
EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. (NCT00557193)
Timeframe: From start of post-induction therapy for up to 10 years
| Intervention | percentage probability (Number) |
|---|
| Arm C (Safety/Efficacy Dose Level 2) | 35.82 |
Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2
Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B. (NCT00557193)
Timeframe: From start of post-induction therapy for up to 10 years.
| Intervention | percent probability (Number) |
|---|
| Arm B (IR/HR MLL-R Chemotherapy) | 38.89 |
| Arm C (IR/HR MLL-R Chemotherapy and Lestaurtinib) | 35.82 |
Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm
Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status. (NCT00557193)
Timeframe: 3 Years from end of Induction)
| Intervention | percent probability (Number) |
|---|
| Arm A (MRD Negative) | 86.05 |
| Arm A (MRD Positive) | 87.5 |
| Arm B (MRD Negative) | 47.37 |
| Arm B (MRD Positive) | 22.73 |
| Arm C (MRD Negative) | 51.85 |
| Arm C (MRD Positive) | 27.03 |
Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy
Summarized with mean and standard deviation for those with available data in Arm C (NCT00557193)
Timeframe: Sampled between weeks 6-12 from start of induction
| Intervention | Activity percentage (Mean) |
|---|
| Arm C (Safety/Efficacy Dose Level 2) | 69.00 |
Dose Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) During the First Cycle of Induction Treatment
Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML (NCT03850535)
Timeframe: Cycle 1 of induction treatment (1 cycle is 28 days)
| Intervention | Participants (Number) |
|---|
| Dose-Escalation Cohort 1 | 2 |
| Dose Escalation Cohort 2 | 4 |
| Dose Escalation Cohort 3 | 0 |
| Post Consolidation Cohort | 0 |
Number of Participants With at Least One Adverse Event
Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML. (NCT03850535)
Timeframe: From Baseline until 28 days after the final dose of study drug (up to 2 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Dose-Escalation Cohort 1 | 4 |
| Dose Escalation Cohort 2 | 9 |
| Dose Escalation Cohort 3 | 6 |
| Post Consolidation Cohort | 4 |
Number of Participants With Grade ≥3 Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Sponsor's decision to prematurely terminate the study was made at the end of the Phase 1. The planned Phase 2 was not initiated. This decision was not based on safety concerns, but rather due to the overall company strategy about the adult AML (NCT03850535)
Timeframe: From Baseline until 28 days after the final dose of study drug (up to 2 years)
| Intervention | Participants (Number) |
|---|
| Dose-Escalation Cohort 1 | 4 |
| Dose Escalation Cohort 2 | 9 |
| Dose Escalation Cohort 3 | 5 |
| Post Consolidation Cohort | 4 |
Complete Response Rate
The complete response rate will be defined as the total number of patients who have defined complete response using study regimen (intensive induction therapy/progressive chemotherapy/stem cell rescue), divided by the number of patients entered in the trial using response-evaluable patients. (NCT00632827)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment Plan | 14 |
Median Time to Response
The time to response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) in months. (NCT00632827)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Treatment Plan | 3.0 |
Overall Survival Rate
Overall Survival will be defined the percentage of participants alive at median follow up of 25 months. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. The analysis is expected to occur up to 60 months after the first patient is entered the trial. (NCT00632827)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment Plan | 75 |
Progression Free Survival
Progression-Free Survival will be defined the percentage of participants alive and progression-free at median follow up of 25 months. Patients will be routinely followed for disease progression and those who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who did not progress or die will be censored at the day of their last treatment assessment. Patients who have not received study regimen or did not have on-study treatment assessments will be censored on the day they entered the trial. Patients who receive chemotherapy for reasons other than documented progression of disease or clinical progression without documented progression will be censored on the earliest date of subsequent therapy (NCT00632827)
Timeframe: Up to 3 years
| Intervention | percentage of partcipants (Number) |
|---|
| Treatment Plan | 65 |
Median Time to Progression
Time to progression (TTP) is defined as the time from treatment after OVA until documented lymphoma progression or receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy) or death due to lymphoma. Patients are to be censored at the time of last followup or death due to another cause (NCT01555541)
Timeframe: Up to 48 months
| Intervention | months (Median) |
|---|
| Treatment | 13.2 |
Number of Participants With Successful Neutrophil Engraftments
Neutrophil engraftment is defined as the first day of 3 consecutive days with absolute neutrophil count of >500 cells/microlitre (uL). Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter (NCT01555541)
Timeframe: Up to 24 months after ASCT
| Intervention | participants (Number) |
|---|
| Treatment | 12 |
Number of Participants With Successful Platelet Engraftments
Platelet engraftment is defined as the first of three consecutive measurements for which the platelet count was > 20,000/uL, and must be at least 24 hours following the last platelet transfusion. Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months after ASCT (NCT01555541)
Timeframe: Up to 24 months after ASCT
| Intervention | participants (Number) |
|---|
| Treatment | 12 |
Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization
CR will be calculated based on the PET/CT scan following 2 cycles of salvage therapy using the revised International Working Group (IWG) Criteria for a lymphoma response. This includes: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, Post-treatment residual mass of any size is permitted as long as it is PET-, Spleen and/or liver, if enlarged before therapy based on physical exam or CT scan, should not be palpable on physical exam and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, If bone marrow was involved by lymphoma before treatment, infiltrate must have cleared on repeat bone marrow biopsy. Biopsy sample must be adequate (with goal of > 20 mm unilateral core). If sample is indeterminate by morphology, it should be negative by immunohistochemistry. A sample that is negative by immunohistochemistry but demonstrates small population of clonal l (NCT01555541)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 10 |
Number of Patients Achieving Mobilization-adjusted Complete Response (maCR)
Number of patients achieving maCR to the treatment upon successful stem cell mobilization, defined as at least 2 x10^6 cluster of differentiation 34 (CD34)+cells/Kg of actual body weight. Patients who require use of plerixafor or an autologous bone marrow harvest are considered mobilization failures and will be treated as non-responders. (NCT01555541)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 10 |
Number of Patients Who Advance From Partial Response (PR) to Complete (CR)
Fluorodeoxyglucose-positron emission tomography (FDG-PET) conversion rate was used determined the number of participants who improved following OVA Treatment. (NCT01555541)
Timeframe: Up to 5 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 2 |
Number of Patients Who Received OVA and Then Met Criteria to Proceed to ASCT and Achieved a CR/Partial Response (PR) Post-ASCT
Determination of CR or PR must meet the revised International Working Group (IWG) Criteria for lymphoma response (NCT01555541)
Timeframe: Up to 5 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 11 |
Overall Survival Rate (OS)
The percentage of participants in the study still alive at time of censoring. The time frame is defined as the time from day 0 of OVA treatment until death as a result of any cause. Patients will be censored at the time of last followup (NCT01555541)
Timeframe: Up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment | 59 |
Progression Free Survival Rate
The percentage of participants in the study still alive at time of censoring. The time frame defined as the time from day 0 of OVA treatment until lymphoma progression, receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy), or death as a result of any cause. Patients will be censored at the time of median follow-up. (NCT01555541)
Timeframe: Up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment | 47 |
Overall Response Rate (ORR)
Percentage of participants with complete response following treatment out of all participants in that particular treatment group. Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count > 1.0 x10^9/L and platelet count >100x10^9/L, and normal bone marrow differential (< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of > 20 x 10^9/L and < 100 x 10^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of > 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures. (NCT00067028)
Timeframe: Up to 6 years
| Intervention | Percentage of Participants (Number) |
|---|
| Clofarabine + Ara-C | 36 |
| Clofarabine + Idarubicin | 44 |
| Clofarabine + Idarubicin + Ara-C | 24 |
Participants With a Response
Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count > 1.0 x10^9/L and platelet count >100x10^9/L, and normal bone marrow differential (< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of > 20 x 10^9/L and < 100 x 10^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of > 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures. (NCT00067028)
Timeframe: Up to 6 years
| Intervention | participants (Number) |
|---|
| CR | CRp | PR |
|---|
| Clofarabine + Ara-C | 4 | 2 | 0 |
,| Clofarabine + Idarubicin | 9 | 5 | 1 |
,| Clofarabine + Idarubicin + Ara-C | 16 | 7 | 1 |
Overall Remission Rate (CR+CRp)
Overall Remission Rate for the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy. (NCT01804101)
Timeframe: Up to day 28
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lower-dose CPX-351) | 10 |
| Arm II (Higher Dose COX-351) | 1 |
Treatment-related Mortality Rate. (TRM)
Estimate whether the 32 units/m2 or the 64 units/m2 or both dose levels of CPX-351 are likely to improve treatment-related mortality (TRM) rate while keeping the CR rate constant in patients with untreated high-risk MDS or non-APL AML at high risk of TRM. (NCT01804101)
Timeframe: Up to 1 month after completion of study treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Lower-dose Liposomal Cytarabine-daunorubicin CPX-351) | 6 |
| Arm II (Closed to Accrual Effective 4/21/14) | 2 |
Event-free Survival
The Kaplan-Meier method will be used to estimate the event-free survival distribution. (NCT01035463)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| All Phase I Participants | 84 |
| All Phase II Participants | 87 |
Maximum Tolerated Dose of Lenalidomide (Phase I)
The Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 3 out of 6 subjects experience dose limiting toxicities during cycle 1. Dose limiting toxicities graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCT01035463)
Timeframe: Cycle 1, 28 days
| Intervention | milligrams PO daily (Number) |
|---|
| Treatment (Stem Cell Transplantation) | 10 |
Overall Survival
The Kaplan-Meier method will be used to estimate the overall survival distribution. This outcome only reports data as it pertains to overall survival at one year. All-cause mortality includes survival for follow up for all subjects on the study. (NCT01035463)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| All Phase I Participants | 100 |
| All Phase II Participants | 95 |
2 Year Event Free Survival
Percentage of patients who were event free at 2 years. The 2-year event free rate was estimated using the Kaplan Meier method. An event is defined as death, progression or treatment failure. (NCT00039130)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Rituximab With High Intensity Chemotherapy | 78 |
2 Year Overall Survival
Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method. (NCT00039130)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Rituximab With High Intensity Chemotherapy | 80 |
Complete Response Rate
Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease. (NCT00039130)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Rituximab With High Intensity Chemotherapy | 83 |
Number of Participants With Response
Patient response defined by: Death, Resistant to Therapy [no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses], or Relapse. (NCT00382590)
Timeframe: Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end
| Intervention | Participants (Number) |
|---|
| Death | Resistant to Therapy | Relapse |
|---|
| 5-Aza + VPA | 0 | 4 | 0 |
,| Ara-C | 0 | 5 | 0 |
Disease-free Survival (DFS)
DFS defined as time from transplantation to disease relapse, disease progression, death during remission, or last follow-up. Evaluation at 3 months and 6 months after transplantation, then every 6 months for 3 years, and then once a year up to 5 years from the transplant date. (NCT00472056)
Timeframe: Up to 5 years from transplant date.
| Intervention | months (Mean) |
|---|
| Standard Dose Rituximab | 11.33 |
| High Dose Rituximab | 9.635 |
Number of Patients That Achieved Complete Response to ABT-751
Complete response (CR) is the occurrence of all of the following on approximately Day 29: less than 5% leukemic blasts in the bone marrow aspirate with no evidence of leukemic blasts in the CSF or peripheral blood and recovery of peripheral blood counts of an Absolute neutrophil count (ANC) > 750/μL and Platelet count > 75,000 μL. (NCT00439296)
Timeframe: Day 29 of Course 1
| Intervention | Participants (Count of Participants) |
|---|
| # of patients not achieving complete response | # of patients who achieved complete response |
|---|
| Dose Level 0 | 1 | 3 |
,| Dose Level 1 | 4 | 1 |
Number of Patients That Experienced Dose Limiting Toxicity From ABT-751
"ABT-751 was given daily for 21 days for a period of 28 day course in combination with dexamethasone, PEG-asparaginase, and doxorubicin. The occurrence of a dose limiting toxicity (DLT) was evaluated at the end of the 28 day course.~DLT will be defined as any of the following events that are deemed by the investigator as probably or definitely attributable to ABT-751. Toxicity grade follows the CTCAE criteria, version 3.0. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).~Grade 3 or 4 Ileus~Grade 3 or 4 Constipation~Grade 3 or 4 Gastrointestinal obstruction, any location~Grade 3 or 4 Sensory Neuropathy~Grade 3 or 4 Motor Neuropathy~Grade 3 or 4 Neuropathic pain lasting longer than 24 hours despite medical intervention~Grade 3 or 4 Hypoxia in the absence of anemia or infection~Grade 4 Alanine aminotransferase (ALT) which does not return to" (NCT00439296)
Timeframe: Each dose level is evaluated
| Intervention | Participants (Count of Participants) |
|---|
| # of patients with DLT | # of patients without DLT |
|---|
| Dose Level 0 | 0 | 4 |
,| Dose Level 1 | 2 | 3 |
Number of Patients With Occurrence of Toxic Death
The occurrence of toxic death at anytime that is definitely, probably or possibly related to the treatment. (NCT00439296)
Timeframe: From the first dose of study therapy until 30 days after last therapy dose. Last dose protocol therapy is on day 21.
| Intervention | Participants (Count of Participants) |
|---|
| # of patients that experienced toxic death | # of patients that did not experience toxic death |
|---|
| Dose Level 0 | 0 | 4 |
,| Dose Level 1 | 0 | 5 |
Number of Participants With Complete Remission
Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery) according to International Working Group (IWG) criteria. (NCT00569010)
Timeframe: 6 weeks
| Intervention | participants (Number) |
|---|
| Low-Dose Ara-C + AZA-Level 0 | 0 |
| Low-Dose Ara-C + AZA-Level 1 | 0 |
| High-Dose Ara-C + AZA-Level 0 | 0 |
| High-Dose Ara-C + AZA-Level 1 | 2 |
Aplasia Rate
Bone marrow aplasia was defined as <20% cellularity and 5% blasts in the bone marrow aspiration evaluation. (NCT00788892)
Timeframe: Day 14 (1st Induction)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: CPX-351 | 55 |
| Arm B: Cytarabine + Daunorubicin | 15 |
Event Free Survival
Event-free survival begins from randomization to the date persistent disease is documented or date of relapse after CR, or death, whichever comes first. (NCT00788892)
Timeframe: Up to 1 year from randomization
| Intervention | days (Median) |
|---|
| Arm A: CPX-351 | 161 |
| Arm B: Cytarabine + Daunorubicin | 55 |
Number of Participants With Complete Remission
Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of >1000/µL and peripheral blood platelets of >100,000/µL in the absence of bone marrow blasts. (NCT00788892)
Timeframe: Within 6 weeks of the last induction treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: CPX-351 | 41 |
| Arm B: Cytarabine + Daunorubicin | 20 |
Overall Survival Rate at 1 Year
Survival defined as the time from randomization to death. (NCT00788892)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Arm A: CPX-351 | 39 |
| Arm B: Cytarabine + Daunorubicin | 18 |
Rate of Stem Cell Transplant
The rate of patients who underwent stem cell transplant. (NCT00788892)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: CPX-351 | 13 |
| Arm B: Cytarabine + Daunorubicin | 10 |
Remission Duration/Time to Remission
"Remission Duration was assessed from the time measurement criteria for CR were met until the first date that disease relapse was objectively documented or the subject died.~Time to remission was measured from the date of randomization to the time measurement criteria for CR were first met." (NCT00788892)
Timeframe: Following achievement of CR over the study period
| Intervention | days (Median) |
|---|
| Remission Duration | Time to Remission |
|---|
| Arm A: CPX-351 | 275 | 49 |
,| Arm B: Cytarabine + Daunorubicin | 235 | 40 |
Disease Free Survival
Median disease-free survival (NCT00839982)
Timeframe: Up to 5 years
| Intervention | median months (Median) |
|---|
| Treatment (Chemotherapy) | 7.4 |
Maximum Tolerated Dose
We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine. (NCT00839982)
Timeframe: up to 5 years
| Intervention | mg/day (Number) |
|---|
| Treatment (Chemotherapy) | 20 |
Number of Patients With Dose Limiting Toxicity
Dose limiting toxicity (DLT) consists of grade 3-4 non-hematologic toxicity at least possibly related to study drug. Exceptions include neutropenic fever; drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin recovering to < grade 2 by 7 days. Prolonged grade 2 myelosuppression lasting longer than 49 days in patients who don't proceed to additional cytotoxic therapy is considered a DLT. The MTD or recommended phase II dose is the highest dose level at which no more than 1 patient out of 6 experiences DLT. (NCT00839982)
Timeframe: Outcomes by day 30
| Intervention | Participants (Count of Participants) |
|---|
| Dose Level 1 | 0 |
| Dose Level 2 | 4 |
| Dose Level 3 | 2 |
| Dose Level 4 | 2 |
Overall Survival
Median overall survival (NCT00839982)
Timeframe: Up to 5 years
| Intervention | median months (Median) |
|---|
| Treatment (Chemotherapy) | 6.8 |
Occurrence of a Dose-Limiting Toxicity
The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. (NCT00928200)
Timeframe: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm | 0 |
Event-Free Survival (EFS)
Number of patients surviving without relapsed/progressive disease (NCT01008462)
Timeframe: 1 Year post-autograft
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Autologous HCT, Donor HCT) | 9 |
Number of Patients Who Engrafted
Number of patients with donor engraftment. (NCT01008462)
Timeframe: Day 84 post-allograft
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Autologous HCT, Donor HCT) | 13 |
Number of Patients Who Had Infections
Number of patients who had infections. (NCT01008462)
Timeframe: 1 Year post-autograft
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Autologous HCT, Donor HCT) | 16 |
Number of Patients With Relapsed/Progressive Disease
"Relapse/Progression defined as:~Nodes, liver, and/or spleen ≥50% increased or new by physical exam / imaging studies.~Circulating lymphocytes ≥50% increased by morphology and/or flow cytometry. Richter's transformation by lymph node biopsy ." (NCT01008462)
Timeframe: 1 year post-autograft
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Autologous HCT, Donor HCT) | 6 |
Overall Survival
Number of patients surviving one year post-autograft (NCT01008462)
Timeframe: 1 year post-autograft
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Autologous HCT, Donor HCT) | 10 |
Non-relapse Mortality (NRM)
Number of patients with non-relapse mortalities. (NCT01008462)
Timeframe: 200 days and 1 Year post-allograft
| Intervention | Participants (Count of Participants) |
|---|
| 200 days | 1 Year |
|---|
| Treatment (Autologous HCT, Donor HCT) | 0 | 1 |
Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease
"aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999).~GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death~CGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD." (NCT01008462)
Timeframe: 1 year post-allograft,
| Intervention | Participants (Count of Participants) |
|---|
| Acute Graft-versus-Host-Disease | Chronic extensive Graft-versus-Host-Disease |
|---|
| Treatment (Autologous HCT, Donor HCT) | 8 | 1 |
Complete Response in the Absence of Platelet Recovery
"Complete response in the absence of platelet recovery is defined as:~- Bone marrow (<5% blasts) with adequate bone marrow cellularity, no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts except for platelets (neutrophil count =1,000/µL)" (NCT01184898)
Timeframe: Within one week of peripheral count recovery but no later than day 42
| Intervention | participants (Number) |
|---|
| Sirolimus and MEC | 2 |
Complete Response
"Complete response is defined as:~Peripheral Blood Counts -Neutrophil count >1 x 109/L.~Platelet count ≥ 100 x 109/L.~Reduced hemoglobin concentration or hematocrit has no bearing on remission status.~Leukemic blasts must not be present in the peripheral blood.~Cellularity of bone marrow biopsy must be > 20% with maturation of all cell lines with < 5% blasts and no Auer rods.~Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present" (NCT01184898)
Timeframe: Within one week of peripheral count recovery but no later than day 42
| Intervention | participants (Number) |
|---|
| Sirolimus and MEC | 11 |
Partial Response
"Partial response is defined as:~Requires that all of the criteria for complete remission be satisfied except that the bone marrow may contain ≥ 5% blasts but < 25% blasts.~A marrow with <5% blasts that contain Auer rods will also be considered a PR" (NCT01184898)
Timeframe: Within one week of peripheral count recovery but no later than day 42
| Intervention | participants (Number) |
|---|
| Sirolimus and MEC | 3 |
Association Between the Magnitude of mTOR Target Inhibition Post-treatment in Leukemic Blasts and Clinical Response in Patients With High Risk AML Treated With Sirolimus MEC
"Percent change compared between response groups (responder vs nonresponder).~This outcome measure only includes patients who survived to outcome assessment." (NCT01184898)
Timeframe: From pre- to post-treatment
| Intervention | percentage change in leukemic blasts (Mean) |
|---|
| Responders (17 pts) | Nonresponders (10 pts) |
|---|
| Sirolimus and MEC | 69 | -36 |
4-year Event Free Survival
Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR. (NCT01363128)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Hyper-CVAD, Ofatumumab) | 41 |
4-Year Overall Survival
Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years. (NCT01363128)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Hyper-CVAD, Ofatumumab) | 47 |
Number of Participants With Complete Remission (CR)
Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR. (NCT01363128)
Timeframe: Up to 8 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Hyper-CVAD, Ofatumumab) | 68 |
Maximal Tolerated Dose (MTD) of Ruxolitinib in Combination With Chemotherapy Defined as the Highest Dose Level at Which no More Than 1 Out of 6 Patients Experience a Dose Limiting Toxicity (Phase I)
The method of Thall, Simon and Estey will be used for toxicity monitoring for this study. The severity of the toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 whenever possible. Safety data will be summarized by category, severity and frequency. (NCT02420717)
Timeframe: 42 days
| Intervention | Milligrams (mg) (Number) |
|---|
| Phase I Ruxolitinib 15mg | 25 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT02420717)
Timeframe: Up to 4 years 7 months
| Intervention | Months (Median) |
|---|
| Phase I Ruxolitinib 15mg | 4.8 |
| Phase I Ruxolitinib 20mg | 5.4 |
| Phase I Ruxolitinib 25mg | 38.5 |
Participants With Complete Response (Complete Response [CR]/CR With Incomplete Marrow Recovery [CRi]) (Phase II)
Complete Response (CR) is disappearance of all clinical and/or radiologic evidence of disease, Neutrophil count ≥ 1.0 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Normal bone marrow differential (≤ 5% blasts), No extra-medullary leukemia. Complete Remission with Incomplete Blood Count Recovery (CRi) is CR except for ANC < 1.0 x 10^9/L and/or platelets < 100 x 10^9/L. (NCT02420717)
Timeframe: 42 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Ruxolitinib 15mg | 0 |
| Phase I Ruxolitinib 20mg | 1 |
| Phase I Ruxolitinib 25mg | 0 |
Progression-free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse. (NCT02420717)
Timeframe: Up to 4 years 7 months
| Intervention | Months (Median) |
|---|
| Phase I Ruxolitinib 15mg | 2.3 |
| Phase I Ruxolitinib 20mg | 1.8 |
| Phase I Ruxolitinib 25mg | 1.9 |
Duration of Relapse-free Survival (for Patients Achieving CR or CRp)
Categorized according to criteria recommended by International Working Groups. (NCT01729845)
Timeframe: Up to 5 years
| Intervention | Days (Median) |
|---|
| Dose Level 2: 7-Days of Decitabine-MEC | 150 |
Overall Survival
Survival measured as of day of last contact. Categorized according to criteria recommended by International Working Groups. (NCT01729845)
Timeframe: Up to 5 years
| Intervention | days (Median) |
|---|
| Dose Level 2: 7-Days of Decitabine-MEC | 564 |
Remission Rate Including CR and CRp
"Complete remission (CR) and Complete remission with incomplete platelet recovery (CRp) categorized according to criteria recommended by International Working Groups:~Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly; hemoglobin level at least 110 g/L, platelet count at least 100x10^9/L, and absolute neutrophil count at least 1.0 x10^9/L. In addition, all 3 blood counts should be no higher than the upper normal limit; Normal leukocyte differential; Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1." (NCT01729845)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Dose Level 2: 7-Days of Decitabine-MEC | 11 |
Most Efficacious and Tolerated Dosage of Decitabine (Period 1)
MTD (most tolerated dose) of decitabine, measured in number of dose limiting toxicities. MTD defined as the highest dose in which the incidence of dose limiting toxicity is < 33%, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) (NCT01729845)
Timeframe: through day 45
| Intervention | Incidents (Number) |
|---|
| Dose-limiting toxiticies | Complete Remission | Complete Remission, incomplete PLT recovery | Complete Remission, incomplete blood count recover | Morphologic leukemia-free state | Resistant Disease | Death (among those who received MEC) |
|---|
| Dose Level 1: 5-Days of Decitabine-MEC | 0 | 1 | 2 | 0 | 0 | 1 | 2 |
,| Dose Level 2: 7-Days of Decitabine-MEC | 0 | 5 | 1 | 1 | 0 | 3 | 1 |
,| Dose Level 3: 10-Days of Decitabine-MEC | 0 | 3 | 2 | 0 | 3 | 4 | 0 |
3-year Event Free Survival (EFS)
We will use the Kaplan-Meier method to describe event-free survival. EFS will be defined as the time from enrollment to death, relapse, or refractory disease with event-free subjects' time censored at the date of last follow-up. (NCT02433483)
Timeframe: 3 years after enrollment of the last participant
| Intervention | Percentage of participants (Number) |
|---|
| Myeloid Malignancies | 0 |
3-year Overall Survival (OS)
We will use the Kaplan-Meier method to describe overall survival. Overall survival will be defined as the time from enrollment to death, with living subjects' time censored at the date of last follow-up (NCT02433483)
Timeframe: 3 years after enrollment of the last participant
| Intervention | Percentage of participants (Number) |
|---|
| Myeloid Malignancies | 0 |
Median Time to Neutrophil Recovery
The time to neutrophil recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of neutrophils, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events. (NCT02433483)
Timeframe: From start of therapy to completion of therapy (approximately 1 year)
| Intervention | Days (Median) |
|---|
| Myeloid Malignancies | 14.5 |
Number of Participants by Stratum Who Complete 2 Cycles of Therapy
If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as >5% donor chimerism at the time of count recovery (ANC > 0.3 x 10^9/L and platelet count > 30 x 10^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability. (NCT02433483)
Timeframe: At the end of therapy cycle 2 (approximately 2-3 months)
| Intervention | Participants (Count of Participants) |
|---|
| Myeloid Malignancies | 0 |
Proportion of Participants Who Experience Therapeutic Success
"All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as:~Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy.~Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy.~In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy." (NCT02433483)
Timeframe: At the end of therapy cycle 2 (approximately 2-3 months)
| Intervention | proportion (Number) |
|---|
| Myeloid Malignancies | 0 |
Time to Platelet Recovery
"The time to platelet recovery will be summarized using descriptive statistics. If there are no deaths prior to recovery of platelets, nonparametric confidence intervals for the median time to recovery will be computed by inverting the sign test. Otherwise, we will compute cumulative incidence curves to describe the time to platelet and neutrophil recovery while adjusting for competing events.~Due to the small number of patients enrolled, the data is presented by patient." (NCT02433483)
Timeframe: From start of therapy to completion of therapy (approximately 1 year)
| Intervention | days (Number) |
|---|
| Myeloid Malignancies | 15 |
1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)
"Children's Oncology Group (COG) Stem Cell Committee Consensus Guidelines for Establishing Organ Stage and Overall Grade of Acute Graft Versus Host Disease (GVHD) were used. Overall clinical grade was based on the highest stage obtained:~Grade 0: no stage 1-4 of any organ~Grade I: stage 1-2 skin and no liver or gut involvement~Grade II: stage 3 skin, or stage 1 liver involvement, or stage 1 GI~Grade III: stage 0-3 skin, with stage 2-3 liver, or stage 2-3 GI~Grade IV: stage 4 skin, liver or GI involvement" (NCT02433483)
Timeframe: From start of therapy through completion of therapy (approximately 1 year)
| Intervention | Participants (Count of Participants) |
|---|
| Stage 0 | Stage I | Stage II | Stage III | Stage IV |
|---|
| Myeloid Malignancies | 0 | 0 | 0 | 2 | 0 |
Percent Donor Chimerism
Percent donor chimerism in blood and bone marrow. (NCT02433483)
Timeframe: At weeks 1, 2, 3, and 4 after infusion of HPC-A
| Intervention | Percentage of donor chimerism (Mean) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 |
|---|
| Myeloid Malignancies | 79.5 | 99 | 99.5 | 100 |
Complete Response Duration
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of 1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease. Response date to loss of response or last follow up. Remission duration will be measured by the estimated median remission duration computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative remission duration drops below 50%, if present. If not present then median remission duration is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis.. (NCT01319981)
Timeframe: Up to 7 years, 8 months
| Intervention | Months (Median) |
|---|
| Hyper-CMAD + Rituximab | NA |
| Hyper-CMAD | NA |
Number of Patients With Complete Remission at One Year
The complete remission (CR) is the total number of patients who are in CR at one year divided by the total number of patients who received at least one dose of HCVAD with liposomal vincristine. CR was defined as the presence of 1x10^9/L neutrophils, >100x10^9/L platelets in the perpherial blood, and no extramedullary disease. (NCT01319981)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Hyper-CMAD + Rituximab | 12 |
| Hyper-CMAD | 13 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. (NCT01319981)
Timeframe: Up to 7 years, 8 months
| Intervention | Months (Median) |
|---|
| Hyper-CMAD + Rituximab | NA |
| Hyper-CMAD | NA |
Complete Response (CR)
"Complete response (CR) was determined the number of participants who achieved CR by Day 42 after induction treatment. The outcome is reported as the total number of participants without dispersion.~• CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence." (NCT02019069)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 2 |
Complete Response With Incomplete Count Recovery (CRi)
"Complete response (CR) with incomplete count recovery (CRi) was determined as the number of participants who achieved CRi after induction therapy. The outcome is reported as the total number or participants without dispersion.~CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.~CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL." (NCT02019069)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 1 |
Duration of Remission (DOR) Following Induction With CPX-351
"Duration of remission (DOR) was assessed as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until documented lost of response, relapse, or death. The outcome is reported as the median with full range.~CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.~CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.~For patients remaining alive, duration of remission (DOR) is reported as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until the most recent assessment." (NCT02019069)
Timeframe: Up to 1 year
| Intervention | days (Median) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 185 |
Early Induction Mortality (Day 30 After 1st Induction)
Early induction mortality was assessed as the number of participants who died within 30 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion. (NCT02019069)
Timeframe: 30 days
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 2 |
Mortality at Day 60 After 1st Induction
Mortality at Day 60 after 1st induction was assessed as the number of participants who died within 60 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion. (NCT02019069)
Timeframe: 60 days
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 3 |
Overall Survival (OS)
Overall survival (OS) was assessed as the number of participants remaining alive 12 months, starting from date of entry into trial. The outcome is reported as the number of participants (without dispersion). (NCT02019069)
Timeframe: At 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 1 |
Participants Experiencing of Serious Adverse Events
Serious adverse events per participant were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the number of participants that experienced any defined SAE, a number without dispersion. (NCT02019069)
Timeframe: Up to 4 weeks after completion of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 5 |
Response Rate (RR)
"The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion.~CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.~CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL." (NCT02019069)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 3 |
Serious Adverse Events
Serious adverse events were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the total number of the defined SAEs, a number without dispersion. (NCT02019069)
Timeframe: Up to 4 weeks after completion of treatment
| Intervention | Adverse events (Number) |
|---|
| Liposomal Cytarabine-daunorubicin CPX-351 | 8 |
Number of Participants With 1 Year Overall Survival
(NCT00345865)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| NHL With Irradiation | 139 |
| HL Without Irradiation | 144 |
| NHL - HIV Infected With Irradiation | 1 |
| NHL - HIV Infected Without Irradiation | 5 |
| NHL Without Radiation and Cyclophosphamide | 128 |
Number of Participants With 1 Year Progression Free Survival
"Progression is defined using the Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.The definition is as follows:~At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy." (NCT00345865)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| NHL With Irradiation | 112 |
| HL Without Irradiation | 102 |
| NHL - HIV Infected With Irradiation | 1 |
| NHL - HIV Infected Without Irradiation | 2 |
| NHL Without Radiation and Cyclophosphamide | 116 |
Number of Participants With 2 Years Overall Survival
(NCT00345865)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| NHL With Irradiation | 124 |
| HL Without Irradiation | 140 |
| NHL - HIV Infected With Irradiation | 1 |
| NHL - HIV Infected Without Irradiation | 4 |
| NHL Without Radiation and Cyclophosphamide | 121 |
Number of Participants With 2 Years Progression Free Survival
"Progression is determined using Response Criteria for Non-Hodgkin's Lymphoma given by NCI Sponsored International Working Group.~Definition is as follows:~At least a 50% increase from nadir of any previously identified abnormal node. Appearance of any new lesion during or at the end of therapy." (NCT00345865)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| NHL With Irradiation | 96 |
| HL Without Irradiation | 91 |
| NHL - HIV Infected With Irradiation | 1 |
| NHL - HIV Infected Without Irradiation | 1 |
| NHL Without Radiation and Cyclophosphamide | 106 |
Number of Participants With Hematopoietic Recovery After Transplantation
return to ANC (absolute neutrophil count) more than 500 cells/milliliter. (NCT00345865)
Timeframe: Day 42
| Intervention | Participants (Count of Participants) |
|---|
| NHL With Irradiation | 171 |
| HL Without Irradiation | 147 |
| NHL - HIV Infected With Irradiation | 2 |
| NHL - HIV Infected Without Irradiation | 5 |
| NHL Without Radiation and Cyclophosphamide | 145 |
Number of Participants Who Survived
Number of Participants Who Survived at day 180. (NCT03019640)
Timeframe: From the time of transplant, assessed up to day 180
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, NK Infusion, Stem Cell Transplant) | 16 |
Treatment-related Mortality Within 30 Days (TRM30)
Participants that had Treatment-related mortality within 30 days. (NCT03019640)
Timeframe: Up to 30 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, NK Infusion, Stem Cell Transplant) | 0 |
Maximum Tolerated Dose (MTD)
MTD is dose level where grade 3-4 sorafenib-attributable toxicity in <2 of 6 participants. Dose-Limiting Toxicity graded according to the NCI Common Toxicity Criteria version 3.0. (NCT00542971)
Timeframe: Twice a week for first two 28 day cycles
| Intervention | milligrams/twice a day (BID) (Number) |
|---|
| Sorafenib + Idarubicin + Ara-C | 400 |
Number of Participants With Complete Response
Complete response was defined by the presence of < 5% blasts in the bone marrow (BM) with > 1 x 10^9/L platelets in the peripheral blood (PB). (NCT00542971)
Timeframe: Baseline to 2 years or disease progression.
| Intervention | Participants (Number) |
|---|
| Complete Response | No Complete Response |
|---|
| Sorafenib + Idarubicin + Ara-C | 54 | 21 |
Complete Response Rate
Complete response rate is defined as the percentage of patients who achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) at the end of induction therapy. (NCT00558519)
Timeframe: Up to 8 years post-registration
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Pediatric Regimen) | 89 |
Disease-free Survival
DFS was defined as time from bone marrow response in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease. (NCT00558519)
Timeframe: Up to 8 years post-registration
| Intervention | months (Median) |
|---|
| Treatment (Pediatric Regimen) | 81.7 |
Event-free Survival
EFS was defined as time from registration in this study to the earliest occurrence of any of the following: failure to achieve bone marrow response (defined using the M bone marrow criteria for acute lymphoblastic leukemia (ALL); if M0 to M1 status (blast cells ,5%) was achieved by the end of induction or extended induction, the patient was considered a responder) by day 60, death, relapse at any site, or development of second malignant disease. (NCT00558519)
Timeframe: Up to 8 years post-registration
| Intervention | months (Median) |
|---|
| Treatment (Pediatric Regimen) | 78.1 |
Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)
The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below. (NCT00558519)
Timeframe: Up to 10 years post-registration
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Pediatric Regimen) | 286 |
Overall Survival
OS was defined from registration to death resulting from any cause. (NCT00558519)
Timeframe: Up to 8 years post-registration
| Intervention | months (Median) |
|---|
| Treatment (Pediatric Regimen) | NA |
Maximum Total Tolerated Dose (MTD) of Daily Combination Fludarabine 30 mg/m^2 and Cytarabine 500 mg/m^2 Among 3 Dose Levels (Dose Level 1: 2 Days, Dose Level 2: 3 Days or Dose Level 3: 4 Days)
Maximum dose levels for Phase I determined among three possible dose levels of Fludarabine and Cytarabine in combination with fixed doses of Oxaliplatin and Rituximab. Fludarabine and Cytarabine Dose Level 1: Days 2-3 (2 Days); Dose Level 2: Days 2-4 (3 Days); and Dose 3: Days 2-5 (4 Days). MTD is dose level at which less than 2/3 or 2/6 participants experience dose limiting toxicities (DLTs). The number of days of fludarabine and cytarabine administration increased simultaneously. Participants received a subsequent cycle of treatment with 1 additional day of fludarabine and cytarabine treatment no less than 4 weeks from the initiation of the previous cycle if no drug-related grade 3 or 4 non-hematologic life-threatening adverse events, and drug-related non-hematologic toxicity resolved to baseline or < grade 2. A maximum of 6 cycles were administered. (NCT00472849)
Timeframe: Up to 36 weeks (6 cycles each 4-6 weeks)
| Intervention | mg/m^2 (Number) |
|---|
| Fludarabine MTD (Total 3 Day Dose) | Cytarabine MTD (Total 3 Day Dose) |
|---|
| OFAR (Phase I) | 90 | 1500 |
Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission
Overall Response includes Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) in high-risk, previously untreated participants with Chronic Lymphocytic Leukemia treated with CFAR using National Cancer Institute - Working Group response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)>1,500/uL, Platelets >100,000uL, Hemoglobin (untransfused) >11.0g/dL, Lymphocytes <4,000/uL and Bone Marrow Aspirate biopsy <30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes >/= 50% decrease,Liver/spleen >/= 50% decrease, symptoms not applicable, PMN >1,500/uL or >50% improvement from baseline, Platelets 100,000uL or >/=50% decrease improvement from baseline, Hemoglobin (untransfused) >11.0g/dL or >50% improvement from baseline, Lymphocytes >50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with <30% lymphocytes with residual disease on biopsy. (NCT00472849)
Timeframe: Up to 36 weeks (6 cycles each 4-6 weeks)
| Intervention | participants (Number) |
|---|
| Complete Remission | Partial Remission | Nodular Partial Remission |
|---|
| OFAR MTD (Phase II) | 3 | 27 | 9 |
Complete Response Rate to 1.3mg/m^2 of Bortezomib With Mitoxantrone and Etoposide in Phase II
"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.~The percentage of participants that experienced complete response will be reported." (NCT00410423)
Timeframe: Up to 7 years
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 - Bortezomib 1.3mg/m^2 | 27 |
Number of Participants With Dose Limiting Toxicity in Phase I
Dose limiting toxicity (DLT) is defined as grade-3 toxicity definitely related to bortezomib or grade-4 toxicity probably or definitely related to bortezomib. (NCT00410423)
Timeframe: 30-90 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1 - Bortezomib 0.7mg/m^2 | 0 |
| Phase 1 - Bortezomib 1.0 mg/m^2 | 0 |
| Phase 1 - Bortezomib 1.3mg/m^2 | 0 |
Disease-free Survival
Number of patients who were free of disease and alive at 1 year. (NCT00609739)
Timeframe: 1 year
| Intervention | Participants (Number) |
|---|
| Cytarabine + Mitoxantrone | 0 |
Patients Who Relapsed
Number of patients whose disease relapsed. (NCT00609739)
Timeframe: 1 Year
| Intervention | participants (Number) |
|---|
| Cytarabine + Mitoxantrone | 1 |
Patients With Graft-Versus-Host-Disease
Number of patients who exhibited acute and/or chronic graft-versus-host disease. (NCT00609739)
Timeframe: Up to 30 Days Post Study Treatment
| Intervention | participants (Number) |
|---|
| Cytarabine + Mitoxantrone | 1 |
Patients With Regimen-Related Toxicity
Number of patients with adverse events related to treatment. (NCT00609739)
Timeframe: Up to 30 Days Post Study Treatment
| Intervention | participants (Number) |
|---|
| Cytarabine + Mitoxantrone | 0 |
Median Percentage of Treg Cells at 1 Year Post Transplant
The investigative intent is to determine the changes in numbers and function of the regulatory cell population using the best methods to measure this cell population. The frequency of T cells will be summarized at baseline and each time point of follow-up. (NCT00578461)
Timeframe: 1 Year
| Intervention | percentage of total CD4+ cells (Median) |
|---|
| Stem Cell Transplant | 4.1 |
Median Percentage of Treg Cells at 1 Year Post Transplant
To define the biologic recovery and behavior of T regulatory cells for patients undergoing stem cell transplantation as specified in this protocol (NCT00578539)
Timeframe: 1 year
| Intervention | percentage of total CD4+ cells (Median) |
|---|
| Stem Cell Transplant | 6.9 |
Disease-free Survival
Disease-free survival is defined as the length of time after treatment ends that the participant survives without any signs or symptoms of that cancer. (NCT00593645)
Timeframe: 5 years from time of restaging
| Intervention | participants (Number) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 0 |
Median Time to Progression
Time to progression is defined as the length of time from the start of treatment until the disease starts to get worse or spread to other parts of the body. (NCT00593645)
Timeframe: 5 years from time of restaging
| Intervention | days (Median) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 152 |
Overall Survival
(NCT00593645)
Timeframe: 5 years from time of restaging
| Intervention | days (Median) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 237 |
Rate of Acute Graft-versus-host Disease (GVHD)
Acute GVHD occurs within 100 days of transplant. (NCT00593645)
Timeframe: Up to 100 days after transplant
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 0 |
Rate of Chronic Graft-versus-host Disease (GVHD)
(NCT00593645)
Timeframe: 100 days-1 year after transplant
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 0 |
Engraftment as Measured by Percent Donor Chimerism
(NCT00593645)
Timeframe: Day +30
| Intervention | participants (Number) |
|---|
| Not done | 50% donor (bone marrow) | 100% donor (bone marrow) | 23.5% donor (FISH) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 2 | 1 | 1 | 1 |
Engraftment as Measured by Percent Donor Chimerism
(NCT00593645)
Timeframe: Day +40-+60
| Intervention | participants (Number) |
|---|
| 60% donor (bone marrow) | 70% donor (bone marrow) | 75% donor (bone marrow) | 100% donor (peripheral blood) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 1 | 1 | 1 | 1 |
Engraftment as Measured by Percent Donor Chimerism
(NCT00593645)
Timeframe: Day +80-+90
| Intervention | participants (Number) |
|---|
| 0% donor | 33% donor - myeloid (peripheral blood) | 67% donor (bone marrow) | 100% donor (bone marrow) |
|---|
| Arm 1: Non-myeloablative Conditioning Regimen | 1 | 1 | 1 | 1 |
Inhibition of NF-kB Target Transcripts and/or Inhibition of Drug Efflux in at Least 50% of Patients
The clinical trial will be based on a sequential monitoring so that we will have a 90% confidence that choline magnesium trisalicylate (CMT) based modulation of NF-kB transcriptional targets and/or drug efflux occurs in at least 50% of patients. (NCT02144675)
Timeframe: 24 hours
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Choline Magnesium Trisalicylate and Chemotherapy) | 13 |
| Arm II (Chemotherapy) | 14 |
3-Year Event-Free Survival (EFS)
3-year EFS was calculated based on the participants with a complete response (CR). Study regimen considered successful if it exhibits a 3-year EFS rate greater than 60% and response rate no less than 90% with Grade III-IV infectious toxicity rate in induction no more than 33%. (NCT00866749)
Timeframe: 3 Years
| Intervention | Participants (Count of Participants) |
|---|
| Augmented BFM Therapy | 68 |
Overall Survival
Overall Survival defined: Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT00866749)
Timeframe: Up to 12 years
| Intervention | Months (Median) |
|---|
| Augmented BFM Therapy | 121 |
Participants With a Complete Response (CR)
Complete Response defined as: Bone Marrow blasts /= 100 and an Absolute Neutrophil Count (ANC) >/= 1000 (NCT00866749)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Augmented BFM Therapy | 108 |
Participants Achieving Negative Minimal Residual Disease (MRD)
To evaluate the prognostic significance of minimal residual disease (MRD) in bone marrow samples of participants who achieved a complete response (CR) at the end of induction (day 29) and at the end of consolidation (day 84) in this group of patients. (NCT00866749)
Timeframe: up to 3 months
| Intervention | participants (Number) |
|---|
| Participants with CR and MRD negative on Day 29 | Participants with CR and MRD negative on day 84 |
|---|
| Augmented BFM Therapy | 60 | 87 |
Acute Graft Versus Host Disease Among Patients Who Received Early Transplant
Acute graft versus host disease (graded II, III, or IV) among patients who received early allogeneic HCT on study. (NCT02756572)
Timeframe: At day 100
| Intervention | Participants (Count of Participants) |
|---|
| Received Allogeneic HCT on Study | 0 |
Demonstrate the Feasibility of Collecting Resource Utilization Data for Trial Participants
The amount of days of hospitalization (the major driver of costs within the first year) will be collected for resource utilization. (NCT02756572)
Timeframe: Within the first year of induction chemotherapy on study
| Intervention | days (Median) |
|---|
| Treatment (Chemotherapy, HCT) | 49 |
Event-free Survival (EFS) Among Patients Who Received Early Transplant
Event-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. Events included death, relapse, and grade 3-4 acute graft vs host disease. (NCT02756572)
Timeframe: Up to 100 days post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 91 |
Event-free Survival (EFS) Among Patients Who Received Early Transplant
Event-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. Events included death, relapse, and grade 3-4 acute graft vs host disease. (NCT02756572)
Timeframe: Up to 6 months post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 82 |
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - AGE
Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of age. (NCT02756572)
Timeframe: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
| Intervention | years (Median) |
|---|
| Received Allogeneic HCT on Study | 55 |
| Did Not Receive Allogeneic HCT on Study | 57 |
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - TREATMENT RELATED MORTALITY
"Patients who receive early transplant will be compared to those that don't using the Wilcoxon rank sum test for the quantitative variable of treatment-related mortality (TRM). This outcome measure is intended to report a predicted TRM score assessed at the time of feasibility evaluation. The TRM score is used to measure treatment-related mortality, or likelihood of death within 28 days of initiation of induction chemotherapy for patients with AML. The score is normalized from 0 to 100, so that a score of 0 demonstrates the patient has a very low likelihood of TRM and a score of 100 a very high likelihood of death. A calculation is used to predict TRM using age, performance status, if they have secondary AML, albumin, creatinine, platelet count, white blood cell count, and peripheral blood blast percentage. The higher the TRM score, the higher the risk of TRM. Calculator and table of relationship between TRM score and TRM probability found here: https://trmcalculator.fredhutch.org/." (NCT02756572)
Timeframe: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
| Intervention | units on a scale (Median) |
|---|
| Received Allogeneic HCT on Study | 2.15 |
| Did Not Receive Allogeneic HCT on Study | 3.045 |
Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant
Overall survival among patients who did not receive early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 100 days after induction day 1
| Intervention | Percentage of participants (Number) |
|---|
| Did Not Receive Allogeneic HCT on Study | 75 |
Overall Survival (OS) Among Patients Who Did Not Receive Early Transplant
Overall survival among patients who did not receive early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 6 months after induction day 1
| Intervention | Percentage of participants (Number) |
|---|
| Did Not Receive Allogeneic HCT on Study | 62 |
Overall Survival (OS) Among Patients Who Received Early Transplant.
Overall survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 100 days post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 91 |
Overall Survival (OS) Among Patients Who Received Early Transplant.
Overall survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 6 months post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 82 |
Relapse-free Survival (RFS) Among Patients Who Received Early Transplant
Relapse-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 100 days post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 91 |
Relapse-free Survival (RFS) Among Patients Who Received Early Transplant
Relapse-free survival among patients who received early allogeneic HCT on study as estimated with the Kaplan-Meier method. (NCT02756572)
Timeframe: Up to 6 months post-transplant
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 82 |
Treatment Related Mortality Among Patients Who Received Early Transplant vs Patients Who Did Not Receive Early Transplant
Treatment related mortality calculated among patients who received early allogeneic HCT on study vs patients who did not receive early transplant on study. (NCT02756572)
Timeframe: At day 100
| Intervention | Percentage of participants (Number) |
|---|
| Received Allogeneic HCT on Study | 9 |
| Did Not Receive Allogeneic HCT on Study | 23.8 |
Demonstrate the Feasibility of Collecting Patient-reported Outcomes for Trial Participants
The amount of returned patient-reported outcome questionnaires will be summarized for each collection timepoint using percent collection from surviving patients for PRO timepoints. (NCT02756572)
Timeframe: Up to 12 months post-HCT
| Intervention | Participants (Count of Participants) |
|---|
| Enrollment PROs returned | Post G-CLAM PROs returned | Pre-HCT PROs returned | 6 months post-HCT PROs returned | 12 months post-HCT PROs returned |
|---|
| Treatment (Chemotherapy, HCT) | 27 | 23 | 8 | 4 | 3 |
Factors That Distinguish Patients Who Received Early Transplant From Those Who Did Not - GENDER
Patients who receive early transplant will be compared to those that don't using the Fisher's exact test for the categorical variables of gender. (NCT02756572)
Timeframe: From time of subject's study enrollment to time of subject's feasibility success assessment (i.e. when subject received transplant within 60 days or when it was determined subject would not proceed with transplant on study)
| Intervention | Participants (Count of Participants) |
|---|
| Female | Male |
|---|
| Did Not Receive Allogeneic HCT on Study | 10 | 11 |
,| Received Allogeneic HCT on Study | 8 | 1 |
Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Enrollment and Incidence of Early Transplant
Success will be defined as enrollment of at least 30 patients with transplants occurring in 15 of these 30 (50%) within 60 days of enrollment or start of induction chemotherapy with G-CLAM, whichever is earlier. (NCT02756572)
Timeframe: Up to 60 days after start of chemotherapy
| Intervention | Participants (Count of Participants) |
|---|
| Received allogeneic HCT on study within 60 days (feasibility success) | Did not receive allogeneic HCT on study within 60 days (feasibility failure) |
|---|
| Treatment (Chemotherapy, HCT) | 9 | 21 |
Feasibility of Early Allogeneic Hematopoietic Cell Transplant Assessed by Relapsed-free Survival 6 Months After Transplant
Success will be defined as observing a 40% of higher 6-month relapse-free survival among patients who received early transplant on study. (NCT02756572)
Timeframe: 6 months after early allogeneic HCT on study
| Intervention | Participants (Count of Participants) |
|---|
| No relapse within 6 months post-HCT (feasibility success) | Relapse within 6 months post-HCT (feasibility failure) |
|---|
| Received Early Allogeneic HCT on Study | 6 | 2 |
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 28
"Complete Remission (CR), defined as <5% blasts in bone marrow with hematologic recovery (ANC>1000/ul and platelets >100,000/ml).~CRi, defined as complete remission with insufficient hematologic recovery (ANC<1000/ul or platelets<100,000/ul).~CRp, defined as complete remission but platelets <100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria.~Morphologic leukemia-free state (MLFS), defined as <5% blasts in bone marrow with no hematologic recovery.~Relapse, defined as >5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease." (NCT02756572)
Timeframe: Approximately 28 days after early allogeneic HCT
| Intervention | Participants (Count of Participants) |
|---|
| CR with MRD | CR without MRD | CRi with MRD | CRi without MRD | MLFS with MRD | MLFS without MRD | Relapse |
|---|
| Received Allogeneic HCT on Study | 0 | 7 | 0 | 1 | 0 | 0 | 0 |
Response Assessments After Early Allogeneic Hematopoietic Cell Transplant, Day 84
"Complete Remission (CR), defined as <5% blasts in bone marrow with hematologic recovery (ANC>1000/ul and platelets >100,000/ml).~CRi, defined as complete remission with insufficient hematologic recovery (ANC<1000/ul or platelets<100,000/ul).~CRp, defined as complete remission but platelets <100,000/ul. Minimal residual disease (MRD), defined as any detectable disease by flow cytometry, cytogenetics, FISH or PCR in a patient otherwise fulfilling remission criteria.~Morphologic leukemia-free state (MLFS), defined as <5% blasts in bone marrow with no hematologic recovery.~Relapse, defined as >5% blasts in bone marrow, flow cytometry, or manual differential; OR treatment for active relapsed disease." (NCT02756572)
Timeframe: Approximately 84 days after early allogeneic HCT
| Intervention | Participants (Count of Participants) |
|---|
| CR with MRD | CR without MRD | CRi with MRD | CRi without MRD | MLFS with MRD | MLFS without MRD | Relapse |
|---|
| Received Allogeneic HCT on Study | 0 | 4 | 0 | 2 | 0 | 0 | 2 |
Phase I - Dose Level With Best Kinetics of Platelet Count Recovery
To describe the kinetics of platelet count recovery in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy who will be receiving eltrombopag. This is assessed graphically by plotting platelet count vs. days relative to start of cytarabine for each patient. (NCT01656252)
Timeframe: 13 months
| Intervention | mg (Number) |
|---|
| Phase I- Cytarabine & Eltrombopag | 150 |
Phase I- Optimal Tolerated Dose of Eltrombopag
To determine the safety, tolerability and optimal dose of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy. The optimal dose was based on rules involving observation of Dose Limiting Toxicity (DLT events), defined as a CTCAE Version 4 non-hematologic adverse event of grade 3 or higher occurring within 30 days of the last dose of eltrombopag judged by the investigator to be at least possibly related to eltrombopag administration. (NCT01656252)
Timeframe: 13 months
| Intervention | mg (Number) |
|---|
| Phase I- Cytarabine & Eltrombopag | 300 |
Response Rate(CR/CRi) Rate
For descriptive purposes, the CR/CRi (complete response/Complete response with incomplete blood count recovery) rate will be reported at the end of the study separately for Arm A and Arm B. Responses are following definitions consistent with those published by Dohner H, Estey EH, Amadori S, et al. CR is defined as Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blasts in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. CRi: All CR criteria except for residual neutropenia (ANC < 1000/μL) (NCT01870596)
Timeframe: Up to 3 years
| Intervention | participants (Number) |
|---|
| Arm A (Cytarabine, Chk1 Inhibitor SCH 900776) | 6 |
| Arm B (Cytarabine) | 9 |
Measure Patient Response to High-dose Cytarabine Followed by Clofarabine in Adult Patients With Relapsed or Refractory AML
Response to the therapy is measured by a defined improvement in Neutrophil and platlet counts, along with improved cellularity of bone marrow biopsy (>20% with maturation of all cell lines), <5% blasts, auer rods must not be detectable and extramedullary leukemia or soft tissue involvment must not be present. (NCT01656031)
Timeframe: 5 weeks
| Intervention | participants (Number) |
|---|
| High-Dose Cytarabine and Clofarabine | 17 |
Disease-free Survival
Number of participants who survived and were disease-free at 5 years (NCT00602225)
Timeframe: At five years after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC) | 11 |
Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0
(NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC) | 2 |
Efficacy
Number of Patients Surviving at Five Years (NCT00602225)
Timeframe: At five years after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC) | 12 |
Maximum Tolerated Dose of Clofarabine
(NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | mg/m^2 of clofarabine (Number) |
|---|
| Arm I: Filgrastim + Clofarabine + Cytarabine (GCLAC) | 25 |
Overall Survival
(NCT00602225)
Timeframe: At five years after the last dose of clofarabine
| Intervention | months (Median) |
|---|
| Arm I | 9 |
Response Rates by Cytogenetic Risk Category and Clofarabine Dose
Number of participants under each Cytogenetic Risk Category and Clofarabine dose who achieve CR (Complete Remission = less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) or CRp (Complete Remission, but with a platelet count of less than 100,000/microL). (NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Favorable Risk + 25 mg/m^2 achieve CR | Intermediate Risk + 15 mg/m^2 achieve CR | Intermediate Risk + 20 mg/m^2 achieve CR | Intermediate Risk + 25 mg/m^2 achieve CR | Intermediate Risk + 25 mg/m^2 achieve CRp | Unfavorable Risk + 15 mg/m^2 achieve CR | Unfavorable Risk + 20 mg/m^2 achieve CR | Unfavorable Risk + 25 mg/m^2 achieve CR | Unfavorable Risk + 25 mg/mg^2 achieve CRp |
|---|
| Arm I | 2 | 2 | 3 | 5 | 4 | 2 | 1 | 6 | 3 |
Response Rates by Cytogenetic Risk Category
Number of participants who achieved Complete Remission (less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) under each cytogenetic risk category. (NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Favorable risk Complete Remission | Intermediate risk Complete remission | Unfavorable risk Complete remission |
|---|
| Arm I | 3 | 10 | 9 |
Response Rates by Duration First Complete Remission (CR1)
Number of participants whose first Complete Remission lasted 0, 1-6, 6-12, or greater than 12 months. Only those participant who had a first CR are included in this data. (NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Duration CR1 (months): 0 | Duration CR1 (months): 1-6 | Duration CR1 (months): 6-12 | Duration CR1 (months): greater than 12 |
|---|
| Arm I | 12 | 4 | 2 | 3 |
Response Rates by Salvage Number
Number of participants in each Salvage number category who achieved a Complete Remission. Salvage number refers to whether treatment with GCLAC on this study was the pariticipant's first salvage regimen (1), second salvage regimen (2), or third or greater salvage regimen (3 or greater). (NCT00602225)
Timeframe: 45 days after the last dose of clofarabine
| Intervention | Participants (Count of Participants) |
|---|
| Salvage number 1 | Salvage number 2 | Salvage number 3 or greater |
|---|
| Arm I | 16 | 5 | 0 |
Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as a disappearance of all target lesions, after Induction. (NCT02668653)
Timeframe: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
| Intervention | Participants (Count of Participants) |
|---|
| Quizartinib | 147 |
| Placebo | 150 |
Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as a disappearance of all target lesions, or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle. (NCT02668653)
Timeframe: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
| Intervention | Participants (Count of Participants) |
|---|
| Quizartinib | 192 |
| Placebo | 176 |
Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure [TF]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: >1000 neutrophils, >100,000 platelets, <5% blasts, and other [defined as absence of extramedullary disease [EMD], blasts with rods, and leukemic blasts]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as ≥5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation. (NCT02668653)
Timeframe: Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment
| Intervention | months (Median) |
|---|
| Quizartinib | 0.03 |
| Placebo | 0.71 |
Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Overall survival is defined as the time from randomization until death from any cause. (NCT02668653)
Timeframe: Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment
| Intervention | months (Median) |
|---|
| Quizartinib | 31.9 |
| Placebo | 15.1 |
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related. (NCT02668653)
Timeframe: Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Gastrointestinal disorders | Diarrhoea | Nausea | Vomiting | Stomatitis | Constipation | Abdominal pain | Dyspepsia | Abdominal pain upper | Infections and infestations | Pneumonia | Sepsis | General disorders and administration site disorders | Pyrexia | Oedema peripheral | Fatigue | Blood and lymphatic system disorders | Febrile neutropenia | Neutropenia | Thrombocytopenia | Anaemia | Metabolism and nutrition disorders | Hypokalaemia | Decreased appetite | Hypomagnesaemia | Hypophosphataemia | Hypocalcaemia | Skin and subcutaneous tissue disorders | Rash | Pruritus | Investigations | Alanine aminotransferase increased | Electrocardiogram QT prolonged | Aspartate aminotransferase increased | Neutrophil count decreased | Respiratory, thoracic, and mediastinal disorders | Cough | Epistaxis | Oropharyngeal pain | Nervous system disorders | Headache | Musculoskeletal and connective tissue disorders | Arthralgia | Back pain | Vascular disorders | Hypertension | Psychiatric disorders | Insomnia |
|---|
| Placebo | 265 | 209 | 94 | 84 | 53 | 56 | 69 | 38 | 23 | 25 | 188 | 41 | 28 | 173 | 109 | 37 | 23 | 143 | 113 | 27 | 30 | 19 | 153 | 96 | 36 | 30 | 24 | 29 | 158 | 66 | 40 | 105 | 27 | 11 | 19 | 12 | 115 | 44 | 29 | 18 | 97 | 53 | 108 | 35 | 28 | 70 | 33 | 50 | 30 |
,| Quizartinib | 264 | 215 | 98 | 90 | 65 | 57 | 56 | 46 | 30 | 29 | 204 | 39 | 15 | 177 | 112 | 30 | 29 | 168 | 117 | 54 | 30 | 29 | 165 | 93 | 46 | 30 | 27 | 26 | 152 | 69 | 35 | 140 | 42 | 36 | 28 | 27 | 123 | 50 | 40 | 27 | 103 | 73 | 91 | 29 | 19 | 71 | 29 | 57 | 37 |
Maximum Tolerated Dose of Dasatinib (Phase I)
Maximum tolerated dose of dasatinib, 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) (NCT01876953)
Timeframe: From the first dose of Dasatinib through the DLT observation period (Day +28)
| Intervention | mg/m2 (Number) |
|---|
| Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | 100 |
CRi Defined as Meeting All Criteria for a Morphologic CR But ANC Remains Less Than 1,000/μL and/or Platelet Count Less Than 100,000/μL
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 0 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
CRiMRD+ Defined as Meeting All Criteria for a CRi But With Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 1 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
CRMRD- Defined as Morphologic CR Without Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 2 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
CRMRD+ Defined as a Morphologic CR But With Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 0 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
Cytogenetic Response Defined as no Detectable Cytogenetic Abnormality in a Subsequent BM Specimen After Induction or Re-induction
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 3 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
Duration of Moderate Neutropenia Defined as an ANC Less Than 1000
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | days (Mean) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 67 |
Duration of Severe Neutropenia Defined as an ANC Less Than 500
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | days (Mean) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 65 |
Duration of Thrombocytopenia Defined as Platelet Count Less Than 100,000
(NCT01607645)
Timeframe: Assessed for up to 5 years
| Intervention | days (Mean) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 51 |
Resistant Disease Defined as Patient Survives at Least 14 Days After Completion of the Last Dose of Induction or Re-induction But Has Persistent Leukemia in Peripheral Blood (PB) or BM
(NCT01607645)
Timeframe: Assessed for up to 90 days
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 1 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 3 |
Severe Prolonged Aplasia
(NCT01607645)
Timeframe: Assessed for up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 0 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
TRM With Each Course of Decitabine-priming, Idarubicin, and Cytarabine
(NCT01607645)
Timeframe: Assessed for up to Day 30
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 0 |
| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 |
Frequency and Severity of Grade 3, 4, and 5 Toxicities With Each Course of Decitabine-priming, Idarubicin, and Cytarabine According to NCI Common Terminology Criteria for Adverse Events Version (CTCAE) 4.0
(NCT01607645)
Timeframe: Assessed for up to 3 months after completion study treatment
| Intervention | Participants (Count of Participants) |
|---|
| CYCLE 1 : Infection Grade 3 | CYCLE 1 : Infection Grade 4 | CYCLE 1 : Hepatobiliary Grade 3 | CYCLE 1 : Blood and Lymphatic Grade 3 | CYCLE 1 : Gastrointenstinal Grade 3 | CYCLE 2 : Infection Grade 3 | CYCLE 2 : Infection Grade 4 | CYCLE 2 : Hepatobiliary Grade 3 | CYCLE 2 : Blood and Lymphatic Grade 3 | CYCLE 2 : Gastrointenstinal Grade 3 |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 1 |
,| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants Who Achieved Morphologic CR
Morphologic complete remission (CR): Absolute Neutrophil Count (ANC)≥1,000/uL, platelet count ≥100,000/uL, <5% Bone Marrow (BM) blasts, no Auer rods (cytoplasmic inclusions which result from an abnormal fusion of the primary (azurophilic) granules), no morphologic dysplasia, and no evidence of extramedullary disease (NCT01607645)
Timeframe: Participants were monitored up until the point when they went off study following completion of the treatment (3 months)
| Intervention | participants (Number) |
|---|
| CR | CRi-MRD (Minimal Residual Disease) | Refractory |
|---|
| Arm I (Decitabine Day -4 to Day 0), Idarubicin, Cytarabine) | 2 | 1 | 1 |
,| Arm II (Decitabine (Day -9 to Day -5), Idarubicin, Cytarabine) | 0 | 0 | 3 |
3-year Event-free Survival Rates in Patients With Relapsed ALL
Estimate the 3-year event-free survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy. (NCT01700946)
Timeframe: 3 years of follow-up since the on-study date
| Intervention | percentage of participants (Number) |
|---|
| STANDARD RISK | 83.3 |
| HIGH RISK | 55.7 |
| All Patients Enrolled on the Study | 67.83 |
3-year Overall Survival Rate of Patients With Relapsed ALL
Estimate the 3-year survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy. (NCT01700946)
Timeframe: 3 years of follow-up since the on-study date
| Intervention | percentage of participants (Number) |
|---|
| STANDARD RISK | 94.4 |
| HIGH RISK | 55.5 |
| All Patients Enrolled on the Study | 72.63 |
Mean of CD20 Expression Levels
To estimate mean levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block I of remission induction therapy for relapsed precursor B-cell ALL. (NCT01700946)
Timeframe: Baseline and at the end of Block I (approximately 5 weeks after the on-study date)
| Intervention | percentage of CD20 Antigen (Mean) |
|---|
| At Baseline | At Block I |
|---|
| All Patients Enrolled on the Study | 36.23 | 19.43 |
,| HIGH RISK | 39.82 | 20.10 |
,| STANDARD RISK | 31.10 | 18.54 |
Median CD20 Expression Levels
To estimate median levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block I of remission induction therapy for relapsed precursor B-cell ALL. (NCT01700946)
Timeframe: Baseline and at the end of Block I (approximately 5 weeks after the on-study date)
| Intervention | percentage of CD20 Antigen (Median) |
|---|
| At Baseline | At Block 1 |
|---|
| All Patients Enrolled on the Study | 22.0 | 15.58 |
,| HIGH RISK | 23.13 | 19.58 |
,| STANDARD RISK | 16.40 | 11.83 |
Cycle 2: Daunorubicin Dose-normalized Plasma: AUC(0-24)
Cycle 2 Daunorubicin AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 10.315 |
| Placebo QD | 8.1146 |
Cycle 2: Daunorubicin Dose-normalized Plasma: Cmax
Cycle 2 Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)
| Intervention | (ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 11.141 |
| Placebo QD | 3.8905 |
Cycle 2: Daunorubicinol Dose-normalized Plasma: AUC(0-24)
Cycle 2 Daunorubicinol AUC(0-24). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 34.067 |
| Placebo QD | 30.820 |
Cycle 2: Daunorubicinol Dose-normalized Plasma: Cmax
Cycle 2 Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 2 Day 1 to Day 2 (0 to 24 post-dose)
| Intervention | (ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 4.0200 |
| Placebo QD | 1.9868 |
Daunorubicin Dose-normalized Plasma: AUC(0-∞)
Daunorubicin AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 8.0807 |
| Placebo QD | 8.7880 |
Daunorubicin Dose-normalized Plasma: AUC(0-t)
Daunorubicin AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 7.9523 |
| Placebo QD | 8.6723 |
Daunorubicin Dose-normalized Plasma: AUC(24-∞)
Daunorubicin AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 0.87496 |
| Placebo QD | 0.72315 |
Daunorubicin Dose-normalized Plasma: AUC(24-t)
Daunorubicin AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 0.76524 |
| Placebo QD | 0.59660 |
Daunorubicin Dose-normalized Plasma: Cmax
Daunorubicin Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 5.1527 |
| Placebo QD | 6.4113 |
Daunorubicinol Dose-normalized Plasma: AUC(0-∞)
Daunorubicinol AUC(0-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 63.997 |
| Placebo QD | 62.835 |
Daunorubicinol Dose-normalized Plasma: AUC(0-t)
daunorubicinol AUC(0-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 62.463 |
| Placebo QD | 61.608 |
Daunorubicinol Dose-normalized Plasma: AUC(24-∞)
Daunorubicinol AUC(24-∞). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 24.537 |
| Placebo QD | 23.039 |
Daunorubicinol Dose-normalized Plasma: AUC(24-t)
Daunorubicinol AUC(24-t). PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 4 to Day 9 (24 to 144 hrs post-dose)
| Intervention | (h*ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 22.963 |
| Placebo QD | 21.821 |
Daunorubicinol Dose-normalized Plasma: Cmax
Daunorubicinol Cmax. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | (ug/ml)/(mg/m2) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 3.5770 |
| Placebo QD | 3.3640 |
Maximum Duration (Days) of Platelet Transfusion Independence
Maximum time period (in days) during which the patient did not receive any platelet transfusion (NCT01890746)
Timeframe: At differnt time points from start of treatment and up to end of study year 2 assessment
| Intervention | Days (Median) |
|---|
| Eltrombopag (ELQ) QD | 29.0 |
| Placebo QD | 29.5 |
Number of Participants Who Achieved Platelet Count Recovery by Day 21
Number of participants with platelet counts 20 Gi/L for 3 consecutive days, unaided by transfusions, in patients with < 20 Gi/L after chemotherapy. (NCT01890746)
Timeframe: By Day 21
| Intervention | Count of participants (Number) |
|---|
| Eltrombopag (ELQ) QD | 4 |
| Placebo QD | 7 |
Number of Participants With Liver Events.
The number of participants with liver enzyme (ALT, AST, ALP, Total bilirubin) abnormalities while receiving study treatment in each arm are presented. (NCT01890746)
Timeframe: 8 weeks
| Intervention | Participants (Number) |
|---|
| Eltrombopag (ELQ) QD | 2 |
| Placebo QD | 6 |
Number of Platelet Transfusions Per Week Within Cycles
This was the average number of platelet transfusions per week within cycles. (NCT01890746)
Timeframe: Post-Base line up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Platelet transfusions per week (Median) |
|---|
| Eltrombopag (ELQ) QD | 1.5 |
| Placebo QD | 1.4 |
Overall Survival (OS)
Overall survival defined as the time form randomization until the date of death due to any cause. (NCT01890746)
Timeframe: From randomization to end of 2-year follow-up
| Intervention | Count of participants (Number) |
|---|
| Eltrombopag (ELQ) QD | 39 |
| Placebo QD | 30 |
Percentage of Patients Who Achieved Platelet Transfusion Independence ≥ 28 Days
Percentage of patients who achieved platelet transfusion independence ≥ 28 days. (NCT01890746)
Timeframe: From start of treatment and up to end of study year 2 assessment
| Intervention | Percentage of participants (Number) |
|---|
| Eltrombopag (ELQ) QD | 55 |
| Placebo QD | 53 |
Plasma Pharmacokinetics (PK) Parameter of Daunorubicin: Half-life (t1/2)
Daunorubicin half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | hour (h) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 15.754 |
| Placebo QD | 13.709 |
Plasma Pharmacokinetics (PK) Parameter of Daunorubicinol: Half-life (t1/2)
Daunorubicinol half-life. PK analyses used actual relative time and actual dosing information in mg/m2. All parameter values were divided by daunorubicin dose in mg/m2 except t1/2. (NCT01890746)
Timeframe: Cycle 1 Day 3 to Day 9 (0 to 144 hrs post-dose)
| Intervention | hour (h) (Geometric Mean) |
|---|
| Eltrombopag (ELQ) QD | 22.735 |
| Placebo QD | 21.603 |
Time to Neutrophil Engraftment
Time to absolute neutrophil count (ANC) >= 0.5 Gi/L for 3 consecutive days in participants with ANC < 0.5 Gi/L after chemotherapy (NCT01890746)
Timeframe: At different time points from last dose of chemotherapy up to end of study year 2 assessment
| Intervention | Months (Median) |
|---|
| Eltrombopag (ELQ) QD | NA |
| Placebo QD | NA |
Time to Platelet Count Recovery >=20 Gi/L
Time to Platelet counts >= 20 Gi/L for 3 consecutive days, unaided by transfusions in patients with < 20 Gi/L after chemotherapy. For this endpoint, the event required platelet count to be >= 20 Gi/L for 3 consecutive days. Hematology was assessed daily during hospital stay but only weekly after hospital discharge and thus, platelet count was not always available for 3 consecutive days to confirm the achievement of platelet count recovery. (NCT01890746)
Timeframe: From last dose of chemotherapy to up to end of study year 2 assessment
| Intervention | Months (Median) |
|---|
| Eltrombopag (ELQ) QD | NA |
| Placebo QD | NA |
Time to Platelet Recovery >=100 Gi/L
Time to platelet counts >= 100 Gi/L unaided by transfusions in participants with < 100 Gi/L after chemotherapy. (NCT01890746)
Timeframe: From last dose of chemotherapy to up to end of study year 2 assessment
| Intervention | Months (Median) |
|---|
| Eltrombopag (ELQ) QD | 0.69 |
| Placebo QD | 0.69 |
Change From Baseline in the Left Ventricular Ejection Fraction (LVEF).
LVEF is a measurement of the percentage of blood leaving heart each time it contracts. LVEF was assessed by an echocardiogram (ECHO) or Multiple Gated Acquisition scan (MUGA). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the Day 42 value minus the Baseline value. (NCT01890746)
Timeframe: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | LVEF percent (Mean) |
|---|
| chnge from baseline (BL) to end of study | change from BL to worse post-BL case |
|---|
| Eltrombopag (ELQ) QD | -2.5 | -4.1 |
,| Placebo QD | -4.3 | -5.7 |
Incidence of Hemorrhagic Events
Incidence of bleeding events using WHO bleeding grade (G0=No bleeding, G1=Petechiae, G2=Mild blood loss, G3=Gross blood loss, G4=Debilitating blood loss) by week and cycle (NCT01890746)
Timeframe: Baseline, weekly within induction and re-induction cycles, end of therapy
| Intervention | Participants (Number) |
|---|
| C1D7 - GRADE 0 | C1D7 - GRADE 1 | C1D7 - GRADE 2 | C1D7 - GRADE 3 | C1D14 - GRADE 0 | C1D14 - GRADE 1 | C1D14 - GRADE 2 | C1D14 - GRADE 3 | C1D21 - GRADE 0 | C1D21 - GRADE 1 | C1D21 - GRADE 2 | C1D21 - GRADE 3 | C1D28 - GRADE 0 | C1D28 - GRADE 1 | C1D28 - GRADE 2 | C1D28 - GRADE 3 | C1D35 - GRADE 0 | C1D35 - GRADE 1 | C1D35 - GRADE 2 | C1D35 - GRADE 3 | C2D1 - GRADE 0 | C2D1 - GRADE 1 | C2D1 - GRADE 2 | C2D1 - GRADE 3 | C2D7 - GRADE 0 | C2D7 - GRADE 1 | C2D7 - GRADE 2 | C2D7 - GRADE 3 | C2D14 - GRADE 0 | C2D14 - GRADE 1 | C2D14 - GRADE 2 | C2D14 - GRADE 3 | C2D21 - GRADE 0 | C2D21 - GRADE 1 | C2D21 - GRADE 2 | C2D21 - GRADE 3 | C2D28 - GRADE 0 | C2D28 - GRADE 1 | C2D28 - GRADE 2 | C2D28 - GRADE 3 | C2D35 - GRADE 0 | C2D35 - GRADE 1 | C2D35 - GRADE 2 | C2D35 - GRADE 3 | Remission visit GRADE 0 | Remission visit GRADE 1 | Remission visit GRADE 2 | Remission visit GRADE 3 |
|---|
| Eltrombopag (ELQ) QD | 58 | 9 | 5 | 1 | 42 | 16 | 5 | 1 | 36 | 13 | 3 | 0 | 31 | 4 | 2 | 0 | 12 | 2 | 0 | 0 | 8 | 1 | 1 | 0 | 9 | 0 | 1 | 0 | 8 | 0 | 0 | 0 | 7 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 56 | 2 | 3 | 1 |
Incidence of Hemorrhagic Events
Incidence of bleeding events using WHO bleeding grade (G0=No bleeding, G1=Petechiae, G2=Mild blood loss, G3=Gross blood loss, G4=Debilitating blood loss) by week and cycle (NCT01890746)
Timeframe: Baseline, weekly within induction and re-induction cycles, end of therapy
| Intervention | Participants (Number) |
|---|
| C1D7 - GRADE 0 | C1D7 - GRADE 1 | C1D7 - GRADE 2 | C1D7 - GRADE 3 | C1D14 - GRADE 0 | C1D14 - GRADE 1 | C1D14 - GRADE 2 | C1D14 - GRADE 3 | C1D21 - GRADE 0 | C1D21 - GRADE 1 | C1D21 - GRADE 2 | C1D21 - GRADE 3 | C1D28 - GRADE 0 | C1D28 - GRADE 1 | C1D28 - GRADE 2 | C1D28 - GRADE 3 | C1D35 - GRADE 0 | C1D35 - GRADE 1 | C1D35 - GRADE 2 | C1D35 - GRADE 3 | C1D42 - GRADE 0 | C1D42 - GRADE 1 | C1D42 - GRADE 2 | C1D42 - GRADE 3 | C2D1 - GRADE 0 | C2D1 - GRADE 1 | C2D1 - GRADE 2 | C2D1 - GRADE 3 | C2D7 - GRADE 0 | C2D7 - GRADE 1 | C2D7 - GRADE 2 | C2D7 - GRADE 3 | C2D14 - GRADE 0 | C2D14 - GRADE 1 | C2D14 - GRADE 2 | C2D14 - GRADE 3 | C2D21 - GRADE 0 | C2D21 - GRADE 1 | C2D21 - GRADE 2 | C2D21 - GRADE 3 | C2D28 - GRADE 0 | C2D28 - GRADE 1 | C2D28 - GRADE 2 | C2D28 - GRADE 3 | C2D35 - GRADE 0 | C2D35 - GRADE 1 | C2D35 - GRADE 2 | C2D35 - GRADE 3 | C2D42 - GRADE 0 | C2D42 - GRADE 1 | C2D42 - GRADE 2 | C2D42 - GRADE 3 | Remission visit GRADE 0 | Remission visit GRADE 1 | Remission visit GRADE 2 | Remission visit GRADE 3 |
|---|
| Placebo QD | 47 | 16 | 6 | 0 | 43 | 13 | 6 | 0 | 43 | 7 | 1 | 1 | 25 | 3 | 0 | 0 | 11 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 8 | 4 | 0 | 0 | 8 | 3 | 0 | 0 | 7 | 3 | 0 | 0 | 7 | 2 | 0 | 0 | 7 | 1 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 58 | 4 | 0 | 0 |
Number of Participants Who Required Medical Resource Utilization
Medical Resource Utilization pertained to unscheduled hospitalizations, unscheduled office visits, unscheduled laboratory tests, and unscheduled procedures. (NCT01890746)
Timeframe: At screening and from start of treatment to end of therapy/remission assessment visit (Day 42 of the latest chemotherapy cycle)
| Intervention | Count of participants (Number) |
|---|
| In-patient hospitalizations/ admissions? | Diagnostic imaging procedures performed? | Health care resources use or emergency visits? | Out-patient lab tests performed? |
|---|
| Eltrombopag (ELQ) QD | 3 | 3 | 8 | 6 |
,| Placebo QD | 4 | 4 | 6 | 6 |
Number of Participants With Any Adverse Events (AE) and Any Serious Adverse Events (SAE) as a Measure of Safety and Tolerability.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function. (NCT01890746)
Timeframe: From the time the first dose of study treatment was administered until 30 days following discontinuation of investigational product regardless of initiation of a new cancer therapy or transfer to hospice
| Intervention | Participants (Number) |
|---|
| Any AE | Any SAE |
|---|
| Eltrombopag (ELQ) QD | 72 | 24 |
,| Placebo QD | 66 | 14 |
Number of Participants With Worst-case Changes From Baseline in Electrocardiogram (ECG) Values
The number of participants with worst case post-baseline changes (normal, abnormal - not clinically significant [NCS], abnormal - clinically significant [NS]) in ECG QT prolonged values are presented. The protocol does not define the criteria for normal, abnormal-NCS and abnormal CS ECG. The outcome was based solely on the investigator interpretation of ECG tracings. (NCT01890746)
Timeframe: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Participants (Number) |
|---|
| Normal | Abnormal - NCS | Abnormal - CS |
|---|
| Eltrombopag (ELQ) QD | 34 | 23 | 2 |
,| Placebo QD | 33 | 29 | 1 |
Number of Participants With Worst-case Changes From Baseline in the Eastern Cooperative Oncology Group (ECOG) Performance Status
The number of participants with worst case post-baseline changes (improved, no change, deteriorated) are presented. (NCT01890746)
Timeframe: Baseline and Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Participants (Number) |
|---|
| Deteriorated | Improved | No Change |
|---|
| Eltrombopag (ELQ) QD | 36 | 0 | 37 |
,| Placebo QD | 36 | 1 | 34 |
Number of Participants With Worst-case Grade Changes From Baseline in the Clinical Chemistry Parameters
The number of participants with a maximum post-baseline grade increase of Grade 3 or Grade 4 from their baseline grade are presented. Clinical Clinical Chemistry parameters included only lab tests that are gradable by CTCAE v4.0. (NCT01890746)
Timeframe: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Participants (Number) |
|---|
| Alanine Aminotransferase, G3 | Albumin, G3 | Aspartate Aminotransferase, G3 | Bilirubin, G3 | Bilirubin, G4 | Calcium Low, G3 | Creatinine, G3 | Creatinine, G4 | Glucose High, G3 | Glucose High, G4 | Magnesium Low, G3 | Magnesium High, G3 | Phosphate, G3 | Phosphate, G4 | Potassium Low, G3 | Potassium Low, G4 | Potassium High, G3 | Potassium High, G4 | Sodium Low, G3 | Urate, G4 |
|---|
| Eltrombopag (ELQ) QD | 1 | 6 | 0 | 1 | 0 | 0 | 0 | 1 | 6 | 0 | 0 | 3 | 10 | 1 | 8 | 0 | 4 | 1 | 3 | 3 |
,| Placebo QD | 5 | 4 | 1 | 4 | 1 | 1 | 1 | 0 | 3 | 1 | 1 | 0 | 19 | 0 | 10 | 2 | 0 | 1 | 4 | 0 |
Number of Participants With Worst-case Grade Changes From Baseline in the Hematology Parameters
The number of participants with a maximum post-baseline grade increase of Grade 3 (G3) or Grade 4 (G4) from their baseline grade are presented. Hematology parameters included only lab tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. (NCT01890746)
Timeframe: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Participants (Number) |
|---|
| Hemoglobin Low, G3 | Leukocytes, G3 | Leukocytes, G4 | Lymphocytes Low, G3 | Lymphocytes Low, G4 | Neutrophils, G4 | Platelets, G3 | Platelets, G4 |
|---|
| Eltrombopag (ELQ) QD | 53 | 10 | 9 | 31 | 35 | 44 | 1 | 63 |
,| Placebo QD | 46 | 10 | 5 | 26 | 38 | 39 | 0 | 56 |
Percentage of Participants With Disease Response Rate and Type of Response
"Disease response as assessed by the investigator using the AML International Working Group Response Assessment at the end of therapy/remission assessment visit; Complete remission (CR): defined as transfusion independence, blood count recovery (Abs. neutrophil count > 1.0 Gi/L and Platelet count > 100.0 Gi/L), no leukemic blast in peripheral blood, Bone Marrow (BM) blasts < 5%, maturation of all cell lines, Auer rods not detectable, and no extramedullary disease.~Partial remission (PR): defined as CR except that for BM blasts where a decrease of at least 50% of BM blasts to 5-25% in BM aspirate is sufficient or BM blasts < 5% with Auer rods present.~Overall response (OR) = CR + PR." (NCT01890746)
Timeframe: Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Overall response | Complete Remission (CR) | Partial Remission (PR) |
|---|
| Eltrombopag (ELQ) QD | 70 | 65 | 5 |
,| Placebo QD | 73 | 70 | 3 |
Summary of Absolute Neutrophil Counts (ANC)
Absolute neutrophil counts over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | Gi/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 |
|---|
| Eltrombopag (ELQ) QD | 0.8 | 0.8 | 0.6 | 0.6 | 0.4 | 0.3 | 0.2 | 0.1 | 0.1 | 0.0 | 0.0 | 0.6 | 4.3 | 2.2 | 0.1 | 0.1 | 0.2 | 0.3 | 0.2 | 0.1 | 0.0 | 0.0 |
Summary of Absolute Neutrophil Counts (ANC)
Absolute neutrophil counts over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | Gi/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C1D42 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 |
|---|
| Placebo QD | 0.5 | 0.6 | 0.5 | 0.4 | 0.2 | 0.2 | 0.1 | 0.1 | 0.0 | 0.0 | 0.0 | 0.3 | 2.7 | 1.7 | 3.1 | 0.0 | 0.2 | 0.5 | 0.5 | 0.1 | 0.1 | 0.1 | 0.0 |
Summary of Hemoglobin
Hemoglobin level over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | g/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 | C2D21 | C2D28 | C2D35 |
|---|
| Eltrombopag (ELQ) QD | 87.6 | 88.0 | 88.0 | 86.0 | 83.0 | 84.0 | 86.0 | 85.0 | 85.3 | 84.5 | 85.0 | 88.0 | 99.0 | 99.0 | 94.5 | 88.5 | 86.5 | 89.0 | 88.0 | 84.0 | 84.5 | 77.5 | 86.0 | 89.0 | 104.0 |
Summary of Hemoglobin
Hemoglobin level over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | g/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C1D42 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 | C2D21 | C2D28 | C2D35 | C2D42 |
|---|
| Placebo QD | 87.0 | 86.0 | 83.0 | 82.0 | 81.5 | 83.0 | 82.0 | 83.0 | 84.0 | 81.5 | 84.0 | 88.0 | 98.0 | 94.0 | 98.0 | 82.5 | 86.5 | 80.0 | 86.5 | 84.0 | 85.0 | 83.0 | 87.0 | 91.0 | 80.0 | 87.0 | 90.5 |
Summary of Platelet Counts Over Time
Platelet counts over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | Gi/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 | C2D21 | C2D28 | C2D35 |
|---|
| Eltrombopag (ELQ) QD | 51.5 | 52.0 | 43.5 | 35.5 | 36.5 | 33.0 | 32.0 | 27.0 | 24.0 | 20.5 | 16.5 | 39.0 | 484.5 | 547.0 | 31.0 | 26.0 | 25.5 | 32.0 | 37.0 | 27.0 | 24.0 | 10.5 | 27.0 | 68.0 | 515.0 |
Summary of Platelet Counts Over Time
Platelet counts over time (NCT01890746)
Timeframe: Baseline, daily then weekly within cycle up to 42 days after last chemotherapy dose, end of therapy /remission assessment visit
| Intervention | Gi/L (Median) |
|---|
| Baseline | C1D1 | C1D2 | C1D3 | C1D4 | C1D5 | C1D6 | C1D7 | C1D8 | C1D9 | C1D14 | C1D21 | C1D28 | C1D35 | C1D42 | C2D1 | C2D2 | C2D3 | C2D4 | C2D5 | C2D6 | C2D7 | C2D14 | C2D21 | C2D28 | C2D35 | C2D42 |
|---|
| Placebo QD | 50.0 | 48.5 | 42.0 | 37.0 | 29.0 | 29.0 | 30.0 | 27.0 | 22.0 | 19.0 | 18.0 | 25.0 | 121.0 | 181.0 | 304.0 | 30.5 | 28.5 | 29.0 | 35.5 | 22.0 | 33.0 | 28.5 | 16.0 | 38.0 | 173.0 | 272.0 | 147.5 |
Worst-case Change From Baseline in Pulse Rate Values
The worst-case post Baseline high and low changes in pulse rate values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline is defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value. (NCT01890746)
Timeframe: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Beats/minute (Mean) |
|---|
| High | Low |
|---|
| Eltrombopag (ELQ) QD | 18.48 | -10.36 |
,| Placebo QD | 17.73 | -11.24 |
Worst-case Post Baseline Change in Blood Pressure Values From Baseline
The worst-case post Baseline high changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the visit value minus the Baseline value. (NCT01890746)
Timeframe: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | millimeter of mercury (mmHg) (Mean) |
|---|
| SBP | DBP |
|---|
| Eltrombopag (ELQ) QD | 14.59 | 9.38 |
,| Placebo QD | 14.34 | 12.61 |
Worst-case Post Baseline Change in Temperature Values From Baseline
The worst-case post Baseline high and low changes in temperature values from Baseline are presented. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Post Baseline was defined as the highest and lowest non-missing post Baseline value respectively. Change from Baseline was calculated as the post Baseline value minus the Baseline value. (NCT01890746)
Timeframe: Baseline and up to Day 42 of the latest chemotherapy cycle (Up to 8 weeks)
| Intervention | Degrees Celsius (Mean) |
|---|
| High | Low |
|---|
| Eltrombopag (ELQ) QD | 0.62 | -0.44 |
,| Placebo QD | 0.77 | -0.63 |
100-Day Treatment-Related Mortality
The cumulative incidence was estimated after taking into account the competing risk of relapse post-ASCT. (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) to death due to any couse, assessed up to 5 years
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 0.9 |
2-Year Cumulative Incidence of Progression
The cumulative incidence was estimated after taking into account the competing risk of early death. (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) to date of first observation of progressive disease or relapsed disease, assessed up to 5 years
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 28 |
2-Year Overall Survival
Overall survival (OS) was measured from peripheral stem cell infusion to death from any cause. It 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.] (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) to death due to any cause, assessed up to 5 years
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 89 |
2-Year Progression-Free Survival
Progression-free survival (PFS) was defined as time from peripheral stem cell infusion 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.] (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) to first observation of progressive disease or death due to any cause, whichever comes first, assessed up to 5 years
| Intervention | Percentage of Participants (%) (Number) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 71 |
Number of Patients With Active Disease at ASCT Achieving CR/PR by Day 100 After ASCT
Responses are assessed using the Revised Criteria for Malignant Lymphoma Response Definitions for Clinical Trials (Cheson et al. 2007). Complete Response (CR) defined as disappearance of all evidence of disease. Partial Response (PR) defined as regression of measurable disease and no new sites. (NCT00695409)
Timeframe: Up to Day 100 post-ASCT
| Intervention | Participants (Count of Participants) |
|---|
| Patients With Active Disease at ASCT | 53 |
Number of Patients With RIT/ZBEAM Developing Therapy Induced MDS and AML
Patient receiving the full treatment of RIT/ZBEAM developed therapy induced MDS or AML. (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) to onset of therapy induced MDS/AML, assessed up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 0 |
Time to Neutrophil Recovery
Neutrophil recovery was defined as the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL. (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) till the first of 3 consecutive days of an absolute neutrophil count ≥ 500/µL.)
| Intervention | Days (Median) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 10 |
Time to Platelet Recovery
Platelet recovery was defined as the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions. (NCT00695409)
Timeframe: From peripheral stem cell infusion (Day0 ASCT) till the first of 7 consecutive days with a platelet count ≥ 20,000/µL with no transfusions
| Intervention | Days (Median) |
|---|
| Treatment (RIT, ZBEAM, ASCT) | 12 |
2-yr Overall Survival
Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up. (NCT00084838)
Timeframe: Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months.
| Intervention | probability (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Modified IRS | 0.70 |
Grade 3-4 Allergy/Immunology
All Grade 3-4 Allergy/Immunology events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 1 |
Grade 3-4 Auditory/Hearing Events
All Grade 3-4 Auditory/Hearing events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 8 |
Grade 3-4 Blood/Bone Marrow Events
"All Grade 3-4 Blood/Bone Marrow events based on CTCAEv2 as reported on case report forms.~Arm Name" (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 564 |
Grade 3-4 Cardiovascular Events
All Grade 3-4 Cardiovascular events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 6 |
Grade 3-4 Constitutional Events
All Grade 3-4 Constitutional events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 22 |
Grade 3-4 Dermatology Events
All Grade 3-4 Dermatology events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 3 |
Grade 3-4 Gastrointestinal Events
All Grade 3-4 Gastrointestinal events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 139 |
Grade 3-4 Hemorrhage Events
All Grade 3-4 Hemorrhage events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 1 |
Grade 3-4 Hepatic Events
All Grade 3-4 Hepatic events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 8 |
Grade 3-4 Infection/Febrile Neutropenia Events
All Grade 3-4 Infection/Febrile Neutropenia events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 49 |
Grade 3-4 Metabolic/Laboratory Events
All Grade 3-4 Metabolic/Laboratory events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 128 |
Grade 3-4 Muscloskeletal Events
All Grade 3-4 Muscloskeletal events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 8 |
Grade 3-4 Neurology Events
All Grade 3-4 Neurology events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 45 |
Grade 3-4 Pain Events
All Grade 3-4 Pain events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 31 |
Grade 3-4 Pulmonary Events
All Grade 3-4 Pulmonary events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 4 |
Grade 3-4 Renal/Genitourinary Events
All Grade 3-4 Renal/Genitourinary events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 4 |
Grade 3/4 Events
All Grade 3-4 events based on CTCAEv2 as reported on case report forms. (NCT00084838)
Timeframe: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy.
| Intervention | adverse events (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Mod IRS III) | 1021 |
Pre-Radiation Therapy Chemotherapeutic Response
"Response pre-RT/post-CT was defined as follows with overall response defined as achieving PR or CR.~Complete Response (CR): Complete resolution of all initially demonstrable tumor on MRI or CT evaluation w/o appearance of any new areas of disease; negative CSF cytology. Partial Response (PR): >/= 50% decrease in the sum of the products of the maximum perpendicular diameters of the tumor (sum LD) relative to baseline w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Stable Disease (SD): <50% decrease in the sum LD w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Progressive Disease (PD): >/= 25% increase in the sum LD relative to baseline, or the appearance of any new areas of disease or appearance of positive cytology after two consecutive negative samples." (NCT00084838)
Timeframe: Assessed at study entry and pre-RT/post-CT at week 7.
| Intervention | proportion of evaluable patients (Number) |
|---|
| Multi-agent Intrathecal and Systemic CT With RT (Modified IRS | 0.58 |
Complete Response Rate
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/cu mm and a platelet count of 100,000/cu mm, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. These criteria are taken from Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-474 (NCT01349972)
Timeframe: 3 years
| Intervention | participants (Number) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 76 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 24 |
Disease-free Survival
Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated. Disease-free survival Overall survival was defined from date of randomization to death or last known follow-up. Event free survival was defined as date of randomization to the first occurrence of persistent AML after 1 cycle of induction, relapse or death. Patients were censored for event free survival if they had received non-protocol therapy or a stem cell transplant. (NCT01349972)
Timeframe: Time from randomization until death from any cause or relapse or recurrence, assessed up to 2 years
| Intervention | years (Median) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 1.46 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 1.85 |
Incidence of Toxicities, Characterized by Number of Events by Treatment and Grade
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. (NCT01349972)
Timeframe: Up to 14 days after completion of study treatment
| Intervention | Number of events (Number) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 156 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 77 |
Number of Patients With Minimal Residual Disease
Comparisons of the treatments with respect to MRD will be based on the number of patients with MRD at day 14 after the start of treatment. (NCT01349972)
Timeframe: From study start to 14 days after the start of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 26 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 24 |
Overall Survival
Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated. (NCT01349972)
Timeframe: 4 years
| Intervention | years (Median) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 1.46 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 1.850 |
Progression-free Survival
Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated. (NCT01349972)
Timeframe: 4 years
| Intervention | years (Median) |
|---|
| Arm I (Alvocidib, Cytarabine, Mitoxantrone Hydrochloride) | 0.81 |
| Arm II (Cytarabine, Daunorubicin Hydrochloride) | 0.28 |
Number of Participants Experiencing Dose Limiting Toxicities (DLTs) at the Maximum Tolerated Dose (MTD) for Decitabine When Given Together With G-CLAM Toxicities (DLTs) (Phase I)
"Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is < 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included~any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection)~any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days)~lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia" (NCT02921061)
Timeframe: Up to 49 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 3 |
Number of Participants Who Achieved Remission (Complete Remission [CR]/CR With Incomplete Peripheral Blood Count Recovery [CRi])
(NCT02921061)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 13 |
Number of Participants With Event-free Survival
(NCT02921061)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 8 |
Number of Participants With Minimal Residual Disease Negative (MRDneg) Complete Remission (Phase II)
Compared to historical controls of filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) alone. A Simon Minimax two-stage design will be used. (NCT02921061)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 13 |
Number of Participants With Overall Survival
(NCT02921061)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 9 |
Number of Participants With Relapse-free Survival
(NCT02921061)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine 20 mg/m2 and G-CLAM) | 8 |
AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
(NCT01546038)
Timeframe: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 17210 |
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
| Intervention | pg/mL (Median) |
|---|
| Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) | 2275.00 |
| Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder) | 3275.00 |
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose)
| Intervention | pg/mL (Median) |
|---|
| Phase 2 Fit (Biomarker, Responder) | 323.00 |
| Phase 2 Fit (Biomarker, Non-Responder) | 362.00 |
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2). (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose)
| Intervention | Normalized expression units (Median) |
|---|
| Phase 2 Fit (Biomarker, Responder) | 10.9 |
| Phase 2 Fit (Biomarker, Non-Responder) | 14.80 |
Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
(NCT01546038)
Timeframe: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
| Intervention | ng/mL (Geometric Mean) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 1252 |
Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin. (NCT01546038)
Timeframe: Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started
| Intervention | Participants (Number) |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 0 |
| Phase 1B: Glasdegib 200 mg + LDAC | 0 |
| Phase 1B: Glasdegib 100 mg + Decitabine | 0 |
| Phase 1B: Glasdegib 200 mg + Decitabine | 0 |
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 1 |
| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 0 |
Overall Survival (OS) at Phase 1B
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose. (NCT01546038)
Timeframe: First dose to Follow-up (4 years)
| Intervention | Months (Median) |
|---|
| Phase 1B: Glasdegib + LDAC | 4.4 |
| Phase 1B: Glasdegib + Decitabine | 11.5 |
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 37.8 |
Overall Survival (OS) at Phase 2 Unfit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant. (NCT01546038)
Timeframe: Randomization to Follow-up (4 years)
| Intervention | Months (Median) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 8.8 |
| Phase 2 Unfit: LDAC Alone | 4.9 |
Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines. (NCT01546038)
Timeframe: 4 years
| Intervention | Percentage of participants (Number) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 18.2 |
| Phase 2 Unfit: LDAC Alone | 2.3 |
Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL). (NCT01546038)
Timeframe: 4 years
| Intervention | Percentage of participants (Number) |
|---|
| Phase 1B: Glasdegib + LDAC | 8.7 |
| Phase 1B: Glasdegib + Decitabine | 28.6 |
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 54.5 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3. (NCT01546038)
Timeframe: Induction Cycle 1/Day 3, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) | 2510.00 |
| Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder) | 3260.00 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in. (NCT01546038)
Timeframe: Induction Cycle 1/Lead-in, 1 Hour Post dose
| Intervention | ng/mL (Median) |
|---|
| Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) | 8.90 |
| Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder) | 10.50 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Induction Cycle 1/Day 10, 1 Hour Post dose
| Intervention | pg/mL (Mean) |
|---|
| Phase 2 Fit (Biomarker, Responder) | 1.20 |
| Phase 2 Fit (Biomarker, Non-Responder) | 6.60 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Induction Cycle 1/Day 3, 1 Hour Post dose
| Intervention | pg/mL (Mean) |
|---|
| Phase 2 Fit (Biomarker, Responder) | 3.20 |
| Phase 2 Fit (Biomarker, Non-Responder) | 10.90 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | pg/mL (Median) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 0.00 |
| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 9.40 |
Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
(NCT01546038)
Timeframe: Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10
| Intervention | ng/mL (Geometric Mean) |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 308.7 |
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose); Cycle 1/Day 1, 1 Hour Post dose
| Intervention | ratio (Median) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 1.60 |
| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 0.50 |
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3. (NCT01546038)
Timeframe: Induction Cycle 1/Day 3, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 20000 |
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here. (NCT01546038)
Timeframe: Cycle 1/Day 1, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 483.00 |
Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
(NCT01546038)
Timeframe: Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
| Intervention | Hours (Median) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 1.67 |
Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 15020 | 16660 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 28600 | 31400 |
Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
(NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| LDAC Cycle 1/Day 2 | LDAC Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 71.10 | 92.28 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 89.35 | 143.9 |
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| LDAC Cycle 1/Day 2 | LDAC Cycle 1/Day 10 | Ara-U Cycle 1/Day 2 | Ara-U Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 62.55 | 65.56 | 2036 | 2283 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 87.49 | 134.8 | 3050 | 3528 |
AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
(NCT01546038)
Timeframe: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Cycle 1/Day 1 | Cycle 1/Day 2 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | 133.4 | NA |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 251.5 | NA |
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported. (NCT01546038)
Timeframe: Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Cytarabine | Ara-U |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 1070 | 28420 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | NA | NA |
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Daunorubicin | Daunorubicinol |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 499.3 | 2152 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 424.9 | 2712 |
AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Induction Cycle 1/Day 3 | Induction Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 9332 | 16300 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 22840 | 26370 |
AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 2/Day 1 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | NA | 17060 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 28380 | NA |
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose)
| Intervention | pg/mL (Median) |
|---|
| BDNF | ICAM-1 (Intercellular cell adhesion molecule-1) | 6CKINE | BAFF (B-cell activating factor) | MIP-3β | Eotaxin-1 (C-C motif chemokine 11) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 2000 | 128000 | 223.50 | 704.50 | 275.00 | 169.00 |
,| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 900 | 161000 | 318.00 | 1295.00 | 414.50 | 0.00 |
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose)
| Intervention | Normalized expression units (Median) |
|---|
| FOXM1 | PTCH1 |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 0.20 | 0.20 |
,| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 0.40 | 0.10 |
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
| Intervention | ng/mL (Geometric Mean) |
|---|
| Daunorubicin | Daunorubicinol |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 275.3 | 195.4 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 341.0 | 233.4 |
Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
(NCT01546038)
Timeframe: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1/Day 1 | Cycle 1/Day 2 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | 113.4 | 127.9 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 174.2 | 121.7 |
Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
| Intervention | ng/mL (Geometric Mean) |
|---|
| Induction Cycle 1/Day 3 | Induction Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 674.2 | 1135 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 1622 | 2371 |
Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 2/Day 1 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | 1718 | 1826 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 2381 | NA |
Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
| Intervention | ng/mL (Geometric Mean) |
|---|
| LDAC Cycle 1/Day 2 | LDAC Cycle 1/Day 10 | Ara-U Cycle 1/Day 2 | Ara-U Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 58.50 | 63.01 | 379.5 | 452.2 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 100.1 | 132.5 | 569.7 | 652.0 |
Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 1074 | 1242 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 1942 | 2577 |
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first. (NCT01546038)
Timeframe: 1 year
| Intervention | Participants (Number) |
|---|
| QTcF interval increase < 30 msec | QTcF interval increase: 30 to < 60 msec | QTcF interval increase >= 60 msec | Maximum QTcF interval < 450 msec | Maximum QTcF interval: 450 to < 480 msec | Maximum QTcF interval: 480 to < 500 msec | Maximum QTcF interval >= 500 msec |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 14 | 6 | 2 | 10 | 10 | 1 | 1 |
,| Phase 1B: Glasdegib + Decitabine | 2 | 3 | 2 | 4 | 2 | 0 | 1 |
,| Phase 1B: Glasdegib + LDAC | 16 | 5 | 0 | 10 | 11 | 0 | 0 |
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first. (NCT01546038)
Timeframe: 1 year
| Intervention | Participants (Number) |
|---|
| QTcF interval increase < 30 msec | QTcF interval increase: 30 to < 60 msec | QTcF interval increase >= 60 msec | Maximum QTcF interval < 450 msec | Maximum QTcF interval: 450 to < 480 msec | Maximum QTcF interval: 480 to < 500 msec | Maximum QTcF interval >= 500 msec |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 41 | 21 | 6 | 46 | 18 | 3 | 1 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 60 | 19 | 4 | 46 | 29 | 3 | 5 |
,| Phase 2 Unfit: LDAC Alone | 12 | 4 | 1 | 8 | 4 | 3 | 2 |
Number of Participants With Disease-related Gene Mutations at Phase 1B
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
| Intervention | Participants (Number) |
|---|
| CEBPA (CCAAT/enhancer-binding protein alpha) | DNMT3A (DNA [cytosine-5]-methyltransferase 3A) | FLT3 (Fms-like tyrosine kinase 3) | FLT3-ITD (FLT3 internal tandem duplications) | IDH1 (Isocitrate dehydrogenase 1) | IDH2 (Isocitrate dehydrogenase 2) | KIT(Tyrosine-protein kinase Kit) | KRAS(Kirsten rat sarcoma 2 viral oncogene homolog) | NPM1 (Nucleophosmin) | NRAS(Neuroblastoma RAS viral oncogene homolog) | RUNX1 (Runt related transcription factor 1) | TET2 (Tet methylcytosine dioxygenase 2) | WT1 (Wilm's tumour tumor suppressor gene1) |
|---|
| Phase 1B: Glasdegib + Cytarabine/Dauno (Biomarker, Responder) | 2 | 0 | 2 | 1 | 0 | 2 | 0 | 0 | 4 | 1 | 1 | 1 | 0 |
,| Phase 1B: Glasdegib + Decitabine (Biomaker,Non-Responder) | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Phase 1B: Glasdegib + LDAC (Biomarker, Non-Responder) | 3 | 2 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 5 | 1 | 3 | 0 |
,| Phase 1B: Glasdegib+Cytarabine/Dauno(Biomarker,Non-Responder) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
| Intervention | Participants (Number) |
|---|
| CEBPA | DNMT3A | FLT3 | FLT3-ITD | IDH1 | IDH2 | KIT | KRAS | NPM1 | NRAS | RUNX1 | TET2 | WT1 |
|---|
| Phase 2 Fit (Biomarker, Responder) | 6 | 12 | 3 | 2 | 2 | 5 | 2 | 0 | 12 | 5 | 7 | 7 | 0 |
,| Phase 2 Fit (Biomarker,Non-Responder) | 3 | 6 | 2 | 1 | 1 | 4 | 1 | 1 | 3 | 1 | 7 | 5 | 1 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 3 | 2 | 1 | 1 | 5 | 2 | 1 | 0 | 2 | 1 | 10 | 7 | 1 |
,| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 5 | 13 | 4 | 2 | 5 | 10 | 2 | 2 | 3 | 4 | 18 | 8 | 2 |
,| Phase 2 Unfit: LDAC Alone (Biomarker, Non-Responder) | 3 | 6 | 0 | 2 | 2 | 5 | 1 | 2 | 1 | 3 | 7 | 8 | 1 |
,| Phase 2 Unfit: LDAC Alone (Biomarker, Responder) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| Grade 1 AEs | Grade 2 AEs | Grade 3 AEs | Grade 4 AEs | Grade 5 AEs | Missing or unknown AEs |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 0 | 3 | 8 | 10 | 1 | 0 |
,| Phase 1B: Glasdegib + Decitabine | 1 | 0 | 1 | 4 | 1 | 0 |
,| Phase 1B: Glasdegib + LDAC | 1 | 2 | 3 | 10 | 7 | 0 |
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| Grade 1 AEs | Grade 2 AEs | Grade 3 AEs | Grade 4 AEs | Grade 5 AEs | Missing or unknown AEs |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 2 | 7 | 3 | 10 | 0 | 0 |
,| Phase 1B: Glasdegib + Decitabine | 2 | 0 | 0 | 4 | 0 | 0 |
,| Phase 1B: Glasdegib + LDAC | 3 | 2 | 7 | 6 | 3 | 0 |
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| Grade 1 AEs | Grade 2 AEs | Grade 3 AEs | Grade 4 AEs | Grade 5 AEs | Missing or unknown AEs |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 0 | 1 | 11 | 52 | 5 | 0 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 2 | 4 | 15 | 39 | 24 | 0 |
,| Phase 2 Unfit: LDAC Alone | 0 | 1 | 8 | 15 | 17 | 0 |
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| Grade 1 AEs | Grade 2 AEs | Grade 3 AEs | Grade 4 AEs | Grade 5 AEs | Missing or unknown AEs |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 0 | 4 | 15 | 46 | 1 | 0 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 4 | 9 | 20 | 34 | 1 | 0 |
,| Phase 2 Unfit: LDAC Alone | 4 | 6 | 3 | 10 | 1 | 0 |
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| AEs | SAEs |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 16 | 10 |
,| Phase 1B: Glasdegib 100 mg + Decitabine | 4 | 4 |
,| Phase 1B: Glasdegib 100 mg + LDAC | 17 | 13 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 6 | 3 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 3 | 2 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 6 | 5 |
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. (NCT01546038)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| AEs | SAEs |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 69 | 35 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 84 | 68 |
,| Phase 2 Unfit: LDAC Alone | 41 | 32 |
Overall Survival (OS) at Phase 2 Fit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose. (NCT01546038)
Timeframe: First dose to Follow-up (4 years)
| Intervention | Months (Median) |
|---|
| Total participants | Participants >= 55 years old | Participants < 55 years old |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 14.9 | 14.7 | NA |
Percentage of Participants With Complete Response (CR) at Phase 2 Fit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines. (NCT01546038)
Timeframe: 4 years
| Intervention | Percentage of participants (Number) |
|---|
| Total participants | Participants >= 55 years old | Participants < 55 years old |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 42.0 | 36.7 | 77.8 |
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative). (NCT01546038)
Timeframe: 4 years
| Intervention | Percentage of participants (Number) |
|---|
| CRi | MLFS | PR | PRi | MR | SD | CRc | CRm |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 10.9 | 7.8 | 1.6 | 1.6 | 10.9 | 6.3 | 35.9 | 37.5 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 5.1 | 2.6 | 6.4 | 1.3 | 6.4 | 16.7 | 11.5 | 16.7 |
,| Phase 2 Unfit: LDAC Alone | 2.6 | 0.0 | 2.6 | 0.0 | 10.5 | 21.1 | 0.0 | 2.6 |
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones). (NCT01546038)
Timeframe: 4 years
| Intervention | Percentage of participants (Number) |
|---|
| mCR | PR | SD | CRi | Unconfirmed SD | Unconfirmed CRi | mCR (CRi not included) | CRc |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 0.0 | 0.0 | 0.0 | 20.0 | 0.0 | 0.0 | 0.0 | 60.0 |
,| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 10.0 | 0.0 | 0.0 | 10.0 | 10.0 | 10.0 | 10.0 | 10.0 |
,| Phase 2 Unfit: LDAC Alone | 0.0 | 0.0 | 33.3 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | pg/mL (Median) |
|---|
| IL-1β | IL-15 (Interleukin-15) |
|---|
| Phase 2 Fit (Biomarker, Non-Responder) | 6.70 | 600 |
,| Phase 2 Fit (Biomarker, Responder) | 9.70 | 700 |
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Cycle 1/Day 1, 1 Hour Post-dose
| Intervention | pg/mL (Median) |
|---|
| Factor VII:activated blood coagulation factor VII | IL-6 (Interleukin-6) |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC (Biomarker, Responder) | 311500 | 0.00 |
,| Phase 2 Unfit: Glasdegib 100 mg+LDAC(Biomarker, Non-Responder) | 234500 | 6.80 |
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | ratio (Median) |
|---|
| CCNE1 | MSI2 |
|---|
| Phase 2 Fit (Biomarker, Non-Responder) | 1.10 | 0.50 |
,| Phase 2 Fit (Biomarker, Responder) | 0.60 | 0.90 |
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | ratio (Median) |
|---|
| CCND2 | MSI2 | PTCH2 |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 0.80 | 0.80 | 0.70 |
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose); Induction Cycle 1/Day 3, 1 Hour Post dose
| Intervention | ratio (Median) |
|---|
| CDKN1A | SMO | PTCH2 | MYCN |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 2.40 | 4.80 | 0.60 | 0.20 |
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here. (NCT01546038)
Timeframe: Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | ratio (Median) |
|---|
| CCND2 | SMO | CCND1 |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 0.70 | 0.40 | 0.40 |
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. (NCT01546038)
Timeframe: Baseline (Induction Cycle 1/Day -3 pre-dose)
| Intervention | pg/mL (Median) |
|---|
| MMP-3 (Matrix metalloproteinase-3) | IL-8 (Interleukin-8) | BDNF (Brain-derived neurotrophic factor) | IL-5 (Interleukin-5) | VEGF (Vascular endothelial growth factor) | MCP-1 (Monocyte chemotactic protein-1) | ITAC:Interferon-inducible T-cell α chemoattractant |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 10200 | 10.7 | 1200 | 0.00 | 88.00 | 180.5 | 0.00 |
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. (NCT01546038)
Timeframe: Induction Cycle 1/Day 10, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| IL-8 | BDNF | IL-5 | VEGF | MCP-1 | ITAC |
|---|
| Phase 1B: Glasdegib + Cytarabine/Daunorubicin | 37.00 | 200 | 99.00 | 51.00 | 684.00 | 0.00 |
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here. (NCT01546038)
Timeframe: Consolidation Cycle 1/Day 1, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| MIP-1β (Macrophage Inflammatory Protein-1β) | BDNF | VEGF | IL-8 | ITAC |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 226.00 | 7000 | 232.50 | 9.90 | 41.50 |
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here. (NCT01546038)
Timeframe: Consolidation Cycle 1/Day 10, Pre-dose
| Intervention | pg/mL (Median) |
|---|
| MIP-1β | MCP-1 | MMP-3 | IL-8 | ITAC |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 239.50 | 581.00 | 12000 | 11.00 | 4.10 |
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here. (NCT01546038)
Timeframe: End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
| Intervention | pg/mL (Median) |
|---|
| MIP-1β | VEGF | MCP-1 |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 338.00 | 133.00 | 277.00 |
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here. (NCT01546038)
Timeframe: Induction Cycle 1/Day 10, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| IL-1β (Interleukin-1β) | IL-6 | Factor VII | BDNF | VEGF | MCP-1 | MMP-3 | IL-8 | IL-5 | ITAC |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 8.50 | 17.00 | 292500 | 300 | 69.00 | 594.00 | 12000 | 55.00 | 85.00 | 0.00 |
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here. (NCT01546038)
Timeframe: Induction Cycle 1/Day 3, 1 Hour Post dose
| Intervention | pg/mL (Median) |
|---|
| Factor VII(activated blood coagulation factor VII) | BDNF | MMP-3 | IL-8 | ITAC |
|---|
| Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin | 318000 | 700 | 21000 | 28.00 | 14.00 |
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm. (NCT01546038)
Timeframe: Cycle 1/Day 10, Pre-dose
| Intervention | pg/mL (Median) |
|---|
| BDNF | ITAC |
|---|
| Phase 2 Unfit: Glasdegib 100 mg + LDAC | 500 | 7.5 |
,| Phase 2 Unfit: LDAC Alone | 200 | 0.00 |
Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 1.75 | 1.34 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 4.00 | 4.00 |
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
| Intervention | Hours (Median) |
|---|
| Daunorubicin | Daunorubicinol |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 0.500 | 1.00 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 0.492 | 0.642 |
Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
(NCT01546038)
Timeframe: Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 1 | Cycle 1/Day 2 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | 0.75 | 0.58 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 0.53 | 0.53 |
Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
| Intervention | Hours (Median) |
|---|
| Induction Cycle 1/Day 3 | Induction Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin | 5.99 | 4.08 |
,| Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin | 6.00 | 1.04 |
Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
(NCT01546038)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 10 | Cycle 2/Day 1 |
|---|
| Phase 1B: Glasdegib 100 mg + Decitabine | 2.00 | 1.03 |
,| Phase 1B: Glasdegib 200 mg + Decitabine | 2.05 | NA |
Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported. (NCT01546038)
Timeframe: Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
| Intervention | Hours (Median) |
|---|
| LDAC Cycle 1/Day 2 | LDAC Cycle 1/Day 10 | Ara-U Cycle 1/Day 2 | Ara-U Cycle 1/Day 10 |
|---|
| Phase 1B: Glasdegib 100 mg + LDAC | 0.250 | 0.325 | 3.97 | 2.00 |
,| Phase 1B: Glasdegib 200 mg + LDAC | 0.250 | 0.250 | 4.00 | 1.99 |
Disease-Free Survival (DFS)
Estimate the DFS at one-year post-transplantation. The event is defined as relapse or death due to relapse. The number of participants who did not relapse up to one year post transplant is reported. (NCT01621477)
Timeframe: one year post transplant
| Intervention | participants (Number) |
|---|
| Treatment | 7 |
Event-Free Survival (EFS)
Estimate the EFS at one-year post-transplantation. The event is defined as relapse or death due to any cause. The number of participants who were alive without relapse at one year post-transplant is reported. (NCT01621477)
Timeframe: one year post transplant
| Intervention | participants (Number) |
|---|
| Treatment | 4 |
Incidence of Malignant Relapse
Estimate the incidence of malignant relapse at one year post-transplant. The number of participants with malignant relapse or progressive disease is given. Relapse was evaluated using standard WHO criteria for each disease. (NCT01621477)
Timeframe: One year post transplantation.
| Intervention | participants (Number) |
|---|
| Treatment | 10 |
Number of Participants With Transplant Related Mortality (TRM)
The number of participants who died due to TRM in the first 100 days post-transplant is given. (NCT01621477)
Timeframe: 100 days post transplant
| Intervention | participants (Number) |
|---|
| Treatment | 2 |
One-year Survival (OS)
Evaluate the number of participants alive at 1 year. The number of participants surviving to one-year post-transplantation is given. (NCT01621477)
Timeframe: One year post transplant
| Intervention | participants (Number) |
|---|
| Treatment | 7 |
Incidence and Severity of Acute Graft Versus Host Disease (GVHD)
The number of participants with acute GVHD is given, organized by grade. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe. (NCT01621477)
Timeframe: 100 days post transplant
| Intervention | participants (Number) |
|---|
| No Acute GVHD | Grade I | Grade II | Grade III | Grade IV |
|---|
| Treatment | 9 | 3 | 1 | 3 | 1 |
Incidence and Severity of Chronic Graft Versus Host Disease (GVHD)
The severity of chronic GVHD will be described. Chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of participants with chronic GVHD is given, organized by severity. (NCT01621477)
Timeframe: 100 days post transplant
| Intervention | participants (Number) |
|---|
| No Chronic GVHD | Mild | Moderate | Severe |
|---|
| Treatment | 15 | 0 | 2 | 0 |
Overall Survival
(NCT00992602)
Timeframe: Time from start of therapy until death, assessed up to 4 years
| Intervention | months (Median) |
|---|
| Treatment (Liposomal Cytarabine, High-dose Methotrexate) | 8.2 |
Survival Free of Neurological Progression, Measured in Weeks
Neurological progression defined by either clinical impression (measured by Karnofsky Performance Status), radiographical response (using Macdonald criteria), or cytologic response (measured by CSF cytology). (NCT00992602)
Timeframe: Time from start of therapy, assessed up to 4 years
| Intervention | weeks (Median) |
|---|
| Treatment (Liposomal Cytarabine, High-dose Methotrexate) | 6 |
Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients
"MRD positive is defined as > or = to 0.1% MRD MRD negative is define as < 0.1% MRD~All these analyses will be descriptive and exploratory and hypotheses generating in nature." (NCT01614197)
Timeframe: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| MRD positive | MRD negative |
|---|
| Dose Level 1 | 3 | 0 |
,| Dose Level 2 | 2 | 1 |
,| Dose Level 3 | 5 | 1 |
,| Dose Level 4 | 2 | 1 |
Maximum Tolerated Dose
The maximum tolerated dose of bismuth Bi 213 monoclonal antibody M195 following cytarabine in patients with advanced myeloid malignancies. (NCT00014495)
Timeframe: 2 years
| Intervention | mCi/kg (Number) |
|---|
| Bismuth Bi 213 Monoclonal Antibody M195 & Cytarabine | 1 |
Overall Response Rate (ORR = Complete Response (CR) + Partial Response (PR)) of Subjects
-For definitions of CR and PR please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification (NCT03623373)
Timeframe: Through completion of treatment (estimated to be 6 months)
| Intervention | Participants (Count of Participants) |
|---|
| Bendamustine/Rituximab/Acalabrutinib/Cytarabine | 10 |
Pre-transplant Complete Response Rate
-For definitions of CR, please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification (NCT03623373)
Timeframe: Through completion of treatment (estimated to be 6 months)
| Intervention | Participants (Count of Participants) |
|---|
| Bendamustine/Rituximab/Acalabrutinib/Cytarabine | 9 |
Stem Cell Mobilization Success Rate With Cytarabine and Rituximab
-Stem cell mobilization success is defined as a yield of >2x10^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis (NCT03623373)
Timeframe: Through 5 courses of apheresis (up to 5 days)
| Intervention | Participants (Count of Participants) |
|---|
| Bendamustine/Rituximab/Acalabrutinib/Cytarabine | 4 |
Safety and Tolerability of Regimen in Subjects With MCL as Measured by Treatment Related Non-hematologic Toxicity of Grade 3 or Higher
-Toxicity is measured using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (NCT03623373)
Timeframe: 30 days following completion of treatment (estimated to be 7 months)
| Intervention | Participants (Count of Participants) |
|---|
| Diarrhea | Infusion related reaction | Upper respiratory infection | Skin infection | Perirectal abscess | Peritoneal infection | Blood bilirubin increased | Ejection fraction decreased | Alanine aminotransferase increased |
|---|
| Bendamustine/Rituximab/Acalabrutinib/Cytarabine | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
The Rate of Complete Remission (CR+CRi)
CR requires: 1. peripheral blood counts: neutrophil count ≥ 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, reduced hemoglobin concentration or hematocrit has no bearing on remission status, and leukemic blasts must not be present in the peripheral blood. 2. bone marrow aspirate and biopsy: maturation of all cell lines must be present, ≤ 5% blasts, auer rods must not be detectable. 3. extramedullary leukemia, such as central nervous system (CNS) or soft tissue involvement, must not be present. CRi requires that all criteria for complete remission be satisfied except patients can have residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L). (NCT00634244)
Timeframe: Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Carboplatin+Topotecan Hydrochloride) | 0.143 |
| Arm B (Alvocidib+Cytarabine+Mitoxantrone) | 0.278 |
| Arm C (Sirolimus+Mitoxantrone+Etoposide+Cytarabine) | 0.15 |
The Rate of Treatment Failure
"The definition of treatment failure will include:~≥ 5% leukemic blasts at the time of pre-consolidation marrow~Death during/following induction chemotherapy (pre-consolidation)~Persisting marrow hypoplasia and pancytopenia for ≥ 2 months after chemotherapy~CNS or extramedullary disease at the time of pre-consolidation~Leukemia persistence after completion of induction treatment. Leukemia persistence is defined as greater than 10% residual blasts on marrow biopsy done 5-7 days after completion of induction chemotherapy" (NCT00634244)
Timeframe: Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.
| Intervention | proportion of participants (Number) |
|---|
| Arm A (Carboplatin+Topotecan Hydrochloride) | 0.86 |
| Arm B (Alvocidib+Cytarabine+Mitoxantrone) | 0.72 |
| Arm C (Sirolimus+Mitoxantrone+Etoposide+Cytarabine) | 0.84 |
Achievement of Complete Remission (CR) at Reinduction
Disease response assessed after chemotherapy from bone marrow aspirates/biopsies and complete blood count. (NCT00939653)
Timeframe: Between Days 22-36 or on Day 43 and weekly thereafter if peripheral counts haven't recovered
| Intervention | Participants (Count of Participants) |
|---|
| Enrolled Patients | 1 |
Death
Number of participants who died. (NCT00939653)
Timeframe: From the first dose of study therapy until 30 days after last therapy dose
| Intervention | Participants (Count of Participants) |
|---|
| Enrolled Patients | 4 |
Complete Remission Rate (CR + CRi)
"Morphologic complete remission (CR): neutrophil count > 1.0 x 109 /L, platelet count ≥ 100 x 109/L, < 5% bone marrow blasts by morphologic review, no Auer rods, no evidence of extramedullary disease. (No requirements for marrow cellularity, hemoglobin concentration).~Morphologic complete remission with incomplete blood count recovery (CRi): same as CR but ANC may be <1000/mcl or platelet count <100,000/mcl~Participants in the phase I portion of the study, treated at the MTD will count towards the phase II accrual goal for evaluation of the primary endpoint." (NCT02416908)
Timeframe: Median follow-up of 34 days
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Schedule A and Phase II | 18 |
Duration of Remission
-Duration of remission (DOR): Defined as the interval from the date complete remission is documented to the date of recurrence. (NCT02416908)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Phase I Schedule A and Phase II | 9.1 |
Event-free Survival
Event-free survival (EFS): Defined as the interval from the date of first dose of study drug to date of treatment failure including progressive disease, recurrence, or discontinuation for any reason (including toxicity, patient preference, initiation of new treatment without documented progression, or death due to any cause). (NCT02416908)
Timeframe: Up to 2 years (median follow-up of 307 days)
| Intervention | months (Median) |
|---|
| Phase I Schedule A and Phase II | 6.1 |
Number of Participants Who Were Able to Undergo Hematopoietic Stem Cell Transplantation
Allogeneic stem cell transplant utilization: the number of patients proceeding to allogeneic transplant within 2 months following end of study without any additional salvage therapy following study treatment. (NCT02416908)
Timeframe: Up to 2 years (median follow-up of 307 days)
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Schedule A and Phase II | 24 |
Overall Survival
Overall survival (OS): Defined as the date of first dose of study drug to the date of death from any cause. OS will be evaluated at 3 month intervals for at least 12 months and up to a maximum of 2 years. (NCT02416908)
Timeframe: Up to 2 years (median follow-up of 307 days)
| Intervention | months (Median) |
|---|
| Phase I Schedule A and Phase II | 7.8 |
Relapse-free Survival
Relapse-free survival (RFS): For patients achieving a complete remission, defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. (NCT02416908)
Timeframe: Median follow-up of 307 days
| Intervention | days (Median) |
|---|
| Phase I Schedule A and Phase II | 152 |
Time to Neutrophil Engraftment
-Time to neutrophil engraftment: Defined as the date of the first dose of study drug to the date that the absolute neutrophil count is >1,000/mm3 (NCT02416908)
Timeframe: Up to 2 years
| Intervention | days (Median) |
|---|
| Phase I Schedule A and Phase II | 28 |
Time to Platelet Engraftment
-Time to platelet engraftment: Defined as the date of the first dose of study drug to the date that the platelet count is >100,000/mm^3 in the absence of platelet transfusions. (NCT02416908)
Timeframe: 56 days
| Intervention | days (Median) |
|---|
| Phase I Schedule A and Phase II | 38 |
Safety and Tolerability of Treatment as Measured by Incidence of Grade 3-4 Adverse Events Occurring in >5% of Participants
-All adverse events will be classified using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 (NCT02416908)
Timeframe: From start of treatment until 30 days following last day of study treatment or until the start of a subsequent treatment for AML, whichever came first (41 days)
| Intervention | Participants (Count of Participants) |
|---|
| Lymphocyte count decreased | White blood cell decreased | Hypophosphatemia | Platelet count decreased | Neutrophil count decreased | Hyponatremia | Anemia | Hyperglycemia | Skin infection | Febrile neutropenia | Sepsis | Hypokalemia | Lung infection | Alanine aminotransferase increased | Oral thrush | Hypoxia | Hypertension | Diarrhea | Nausea | Edema limbs | Catheter-related infection | Hematuria | Respiratory failure |
|---|
| Phase I Schedule A and Phase II | 32 | 28 | 26 | 22 | 21 | 18 | 14 | 11 | 10 | 8 | 8 | 8 | 7 | 5 | 4 | 4 | 4 | 3 | 3 | 3 | 3 | 3 | 3 |
Number of Participants With Complete Response
Complete Response (CR) is required bone marrow blasts ≤5% and recovery of normal hematopoiesis with an absolute neutrophil count (ANC) of 1*10^9/L or more and platelet count of 100*10^9/L or more; and a complete response without platelets (CRp) is the same criteria as CR but with platelet counts from 20*10^9/L to less than 100*10^9/L. (NCT00096122)
Timeframe: 21 Day Cycle
| Intervention | Participants (Number) |
|---|
| CR | CRp |
|---|
| Idarubicin, Cytarabine + Tipifarnib | 61 | 9 |
The Rate of Major Cytogenetic Response at 6 Months
Cytogenetic response is defined in terms of the percentage of Philadelphia (Ph) chromosome. Major cytogenetic response is defined as 0-34% Ph-positive cells. (NCT00022490)
Timeframe: 6 months
| Intervention | Participants (Number) |
|---|
| Cytarabine/ Imatinib Mesylate | 5 |
2-year Disease-free Survival (DFS)
Measured from data of randomization to post-consolidation therapy until relapse from complete response or death from any cause, with observations censored at the date of last contact for patients last known to be alive without report of relapse. (NCT00085709)
Timeframe: After completing any treatment, every 6 months for 2 years, than annually for years 3-5
| Intervention | Percentage of population (Number) |
|---|
| Post-consolidation GO | 39 |
| Post-consolidation Observation | 50 |
Complete Remission
(NCT00085709)
Timeframe: After induction therapy was completed (1 or 2 months)
| Intervention | participants (Number) |
|---|
| Ara-C+Daunomycin | 203 |
| Ara-C+Daunomycin+Mylotarg | 207 |
Toxicity
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00085709)
Timeframe: For induction, daily for the first 10 days, then twice weekly until consolidation treatment. Weekly during consolidation treatment. Weekly if randomized to post-consolidation G.O.
| Intervention | Participants with a given type of AE (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT (serum glut. oxaloacetic transaminase) | Acidosis (metabolic or respiratory) | Adult respiratory distress syndrome (ARDS) | Albumin, serum-low (hypoalbuminemia) | Alkaline phosphatase | Alkalosis (metabolic or respiratory) | Allergic reaction/hypersens. (inc drug fever) | Amylase | Anorexia | Apnea | Ataxia (incoordination) | Bicarbonate, serum-low | Bilirubin (hyperbilirubinemia) | Blood/Bone Marrow-Other (Specify) | Bronchospasm, wheezing | Calcium, serum-low (hypocalcemia) | Cardiac Arrhythmia-Other (Specify) | Cardiac General-Other (Specify) | Cardiac troponin I (cTnI) | Cardiac troponin T (cTnT) | Cardiac-ischemia/infarction | Colitis | Colitis, infectious (e.g., Clostridium difficile) | Confusion | Constipation | Cough | Creatinine | DIC (disseminated intravascular coagulation) | Death not assoc with CTCAE term-Multi-organ failu | Dehydration | Diarrhea | Distention/bloating, abdominal | Dizziness | Dysphagia (difficulty swallowing) | Dyspnea (shortness of breath) | Edema, larynx | Edema: limb | Edema: viscera | Enteritis (inflammation of the small bowel) | Esophagitis | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Fever (in the absence of neutropenia) | Fistula, GI - Rectum | Fistula, GU - Vagina | Flu-like syndrome | GGT (gamma-glutamyl transpeptidase) | Glucose, serum-high (hyperglycemia) | Glucose, serum-low (hypoglycemia) | Hematoma | Hemoglobin | Hemolysis | Hemorrhage, CNS | Hemorrhage, GI - Abdomen NOS | Hemorrhage, GI - Jejunum | Hemorrhage, GI - Lower GI NOS | Hemorrhage, GI - Oral cavity | Hemorrhage, GI - Rectum | Hemorrhage, GU - Bladder | Hemorrhage, GU - Kidney | Hemorrhage, GU - Urinary NOS | Hemorrhage, GU - Uterus | Hemorrhage, GU - Vagina | Hemorrhage, pulmonary/upper respiratory - Lung | Hemorrhage, pulmonary/upper respiratory - Nose | Hemorrhage/Bleeding-Other (Specify) | Hepatobiliary/Pancreas-Other (Specify) | Hiccoughs (hiccups, singultus) | Hypertension | Hypotension | Hypoxia | Infec with Grade 3 or 4 neut - Abdomen NOS | Infec with Grade 3 or 4 neut - Anal/perianal | Infec with Grade 3 or 4 neut - Appendix | Infec with Grade 3 or 4 neut - Bladder (urin | Infec with Grade 3 or 4 neut - Blood | Infec with Grade 3 or 4 neut - Bone (osteomy | Infec with Grade 3 or 4 neut - Brain + Spina | Infec with Grade 3 or 4 neut - Bronchus | Infec with Grade 3 or 4 neut - Catheter-rela | Infec with Grade 3 or 4 neut - Cecum | Infec with Grade 3 or 4 neut - Colon | Infec with Grade 3 or 4 neut - Dental-tooth | Infec with Grade 3 or 4 neut - Heart (endoca | Infec with Grade 3 or 4 neut - Lip/perioral | Infec with Grade 3 or 4 neut - Liver | Infec with Grade 3 or 4 neut - Lung (pneumon | Infec with Grade 3 or 4 neut - Meninges (men | Infect with Grade 3 or 4 neut - Mucosa | Infec with Grade 3 or 4 neut - Nerve-periphe | Infec with Grade 3 or 4 neut - Oral cavity-g | Infec with Grade 3 or 4 neut - Pelvis NOS | Infec with Grade 3 or 4 neut- Pharynx | Infec with Grade 3 or 4 neut - Rectum | Infec with Grade 3 or 4 neut - Sinus | Infec with Grade 3 or 4 neut - Skin (celluli | Infec with Grade 3 or 4 neut - Small bowel N | Infec with Grade 3 or 4 neut - Upper airway | Infection with Grade 3 or 4 neut - Urinary tract | Infec with Grade 3 or 4 neut - Vulva | Infec with Grade 3 or 4 neut - Wound | Infec with normal ANC or Grade 1/2 neut - Blood | Infec with norm ANC or Gr 1/2 neut, Catheter-rel | Infec with norm ANC or Grade 1/2 neut - Colon | Infec with norm ANC or Gr 1/2 neutr- Dental-tooth | Infec with norm ANC or Gr 1/2 neut - Heart | Infec with norm ANC or Gr 1/2 neutrophils - Liver | Infec with norm ANC or Gr 1/2 neut-Lung (pneumoni) | Infec with norm ANC or Gr 1/2 neut - Muscle | Inf with norm ANC or Gr 1/2 neut-Oral cavity-gums | Infec with norm ANC or Gr 1/2 neut - Scrotum | Infec with norm ANC or Gr 1/2 neut-Skin | Infec with norm ANC or Gr 1/2 neut-Urinary tract | Infection with unknown ANC - Blood | Infection with unknown ANC - Catheter-related | Infection with unknown ANC - Dental-tooth | Infection with unknown ANC - Joint | Infection with unknown ANC - Liver | Infection with unknown ANC - Lung (pneumonia) | Infection with unknown ANC - Mucosa | Infection with unknown ANC - Sinus | Infection with unknown ANC - Skin (cellulitis) | Infection with unknown ANC - Urinary tract NOS | Infection with unknown ANC - Wound | Infection-Other (Specify) | Left ventricular diastolic dysfunction | Left ventricular systolic dysfunction | Leukocytes (total WBC) | Leukoencephalopathy (radiolographic findings) | Liver dysfunction/failure (clinical) | Lymphopenia | Magnesium, serum-low (hypomagnesemia) | Metabolic/Laboratory-Other (Specify) | Mood alteration - anxiety | Mood alteration - depression | Mucositis/stomatitis (clinical exam) - Esophagus | Mucositis/stomatitis (clinical exam) - Large bowel | Mucositis/stomatitis (clinical exam) - Larynx | Mucositis/stomatitis (clinical exam) - Oral cavity | Mucositis/stomatitis (clinical exam) - Pharynx | Mucositis/stomatitis (func/sympt) - Esophagus | Mucositis/stomatitis (func/sympt)- Oral cavity | Mucositis/stomatitis (func/sympt) - Pharynx | Muscle weakness (func/sym, Whole body/generalized | Nasal cavity/paranasal sinus reactions | Nausea | Necrosis, GI - Rectum | Neurology-Other (Specify) | Neuropathy: motor | Neuropathy: sensory | Neutrophils/granulocytes (ANC/AGC) | Nystagmus | Obstruction/stenosis of airway - Trachea | Ocular/Visual-Other (Specify) | Opportunistic infec assoc with Gr 2 lymphopenia | PTT (Partial thromboplastin time) | Pain - Abdomen NOS | Pain - Anus | Pain - Back | Pain - Bone | Pain - Chest/thorax NOS | Pain - Extremity-limb | Pain - Eye | Pain - Head/headache | Pain - Joint | Pain - Muscle | Pain - Oral-gums | Pain - Rectum | Pain - Throat/pharynx/larynx | Pain-Other (Specify) | Pancreatic endocrine: glucose intolerance | Perforation, GI - Colon | Pericardial effusion (non-malignant) | Pericarditis | Petechiae/purpura | Phosphate, serum-low (hypophosphatemia) | Platelets | Pleural effusion (non-malignant) | Pneumonitis/pulmonary infiltrates | Portal vein flow | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Proctitis | Pulmonary/Upper Respiratory-Other (Specify) | Rash/desquamation | Renal failure | Rigors/chills | Seroma | Serum sickness | Sodium, serum-high (hypernatremia) | Sodium, serum-low (hyponatremia) | Somnolence/depressed level of consciousness | Atrial fibrillation | Sinus tachycardia | Supraventricular arrhythmia NOS | Syncope (fainting) | Syndromes-Other (Specify) | Thrombosis/embolism (vascular access-related) | Thrombosis/thrombus/embolism | Thrombotic microangiopathy | Tumor lysis syndrome | Typhlitis (cecal inflammation) | Uric acid, serum-high (hyperuricemia) | Vasovagal episode | Ventricular arrhythmia - Ventricular fibrillation | Vision-blurred vision | Vomiting |
|---|
| Ara-C Consolidation | 22 | 17 | 2 | 2 | 3 | 2 | 0 | 0 | 1 | 2 | 1 | 2 | 0 | 4 | 2 | 0 | 3 | 1 | 0 | 0 | 3 | 4 | 1 | 4 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 4 | 1 | 3 | 0 | 10 | 0 | 1 | 0 | 0 | 0 | 22 | 183 | 16 | 0 | 0 | 1 | 4 | 15 | 0 | 1 | 144 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 4 | 12 | 0 | 0 | 2 | 4 | 6 | 0 | 4 | 0 | 4 | 47 | 1 | 0 | 1 | 13 | 1 | 2 | 3 | 0 | 0 | 1 | 22 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 9 | 1 | 0 | 6 | 1 | 0 | 6 | 4 | 1 | 0 | 1 | 0 | 9 | 0 | 0 | 1 | 0 | 0 | 7 | 1 | 0 | 2 | 1 | 2 | 1 | 0 | 3 | 0 | 0 | 4 | 1 | 2 | 151 | 1 | 0 | 50 | 1 | 4 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 2 | 0 | 7 | 1 | 1 | 2 | 1 | 193 | 0 | 1 | 0 | 0 | 1 | 3 | 1 | 1 | 4 | 2 | 1 | 1 | 8 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 6 | 226 | 3 | 5 | 0 | 0 | 19 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 4 | 2 | 1 | 4 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 5 |
,| Ara-C+Daunomycin | 11 | 11 | 0 | 0 | 10 | 2 | 1 | 0 | 0 | 13 | 0 | 0 | 0 | 11 | 1 | 0 | 7 | 0 | 2 | 1 | 0 | 1 | 6 | 10 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 19 | 0 | 0 | 1 | 6 | 1 | 0 | 0 | 0 | 3 | 25 | 196 | 8 | 0 | 0 | 0 | 0 | 12 | 0 | 1 | 87 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 5 | 0 | 1 | 3 | 1 | 2 | 0 | 2 | 1 | 1 | 25 | 0 | 1 | 1 | 6 | 0 | 2 | 2 | 1 | 0 | 1 | 27 | 0 | 2 | 0 | 3 | 0 | 1 | 1 | 3 | 3 | 1 | 0 | 6 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 3 | 1 | 1 | 0 | 0 | 2 | 0 | 1 | 3 | 1 | 1 | 4 | 0 | 1 | 96 | 0 | 1 | 23 | 1 | 5 | 0 | 1 | 1 | 1 | 1 | 11 | 2 | 2 | 9 | 2 | 1 | 0 | 13 | 0 | 1 | 0 | 0 | 110 | 1 | 0 | 1 | 2 | 0 | 5 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 9 | 130 | 1 | 1 | 0 | 2 | 15 | 1 | 0 | 9 | 6 | 0 | 0 | 0 | 0 | 15 | 0 | 1 | 0 | 0 | 3 | 0 | 1 | 4 | 1 | 2 | 4 | 0 | 0 | 0 | 1 | 5 |
,| Ara-C+Daunomycin+Mylotarg | 29 | 32 | 2 | 7 | 15 | 3 | 1 | 6 | 0 | 14 | 0 | 0 | 1 | 14 | 0 | 1 | 13 | 0 | 0 | 0 | 0 | 2 | 2 | 8 | 3 | 1 | 0 | 3 | 2 | 1 | 0 | 5 | 0 | 2 | 1 | 10 | 1 | 0 | 1 | 1 | 1 | 24 | 178 | 6 | 1 | 1 | 0 | 1 | 22 | 1 | 1 | 101 | 0 | 5 | 0 | 1 | 0 | 1 | 1 | 2 | 1 | 1 | 0 | 1 | 5 | 3 | 8 | 3 | 0 | 2 | 5 | 8 | 1 | 0 | 0 | 2 | 30 | 0 | 0 | 0 | 5 | 0 | 5 | 1 | 1 | 1 | 0 | 22 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 2 | 4 | 0 | 1 | 6 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 6 | 1 | 0 | 0 | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 1 | 4 | 1 | 0 | 4 | 0 | 1 | 106 | 0 | 4 | 21 | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 6 | 2 | 0 | 4 | 1 | 0 | 1 | 7 | 0 | 1 | 0 | 1 | 111 | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 1 | 0 | 2 | 0 | 0 | 8 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 6 | 10 | 145 | 1 | 3 | 2 | 4 | 21 | 0 | 1 | 6 | 8 | 0 | 1 | 0 | 2 | 8 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 4 | 0 | 2 | 3 | 1 | 0 | 1 | 0 | 2 |
,| Post-consolidation G.O. | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 22 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 41 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 43 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 40 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Number of Patients With Dose-Limiting Toxicity (DLT)
Treatment related toxicities that preclude proceeding to HSCT by day 56 of the treatment course. (NCT01158885)
Timeframe: Beginning with the first dose of investigational product until day 56 of treatment course, an average of 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm | 0 |
AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State
AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol·h/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 188 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 615 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | NA |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4460 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 5140 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4750 |
AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
AUC (0-inf) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 (NCT00632749)
Timeframe: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
| Intervention | ng·h/mL (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 104 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 122 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 102 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 85.4 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 65.9 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 68.1 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 62.0 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | NA |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | NA |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 71.2 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 72.7 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 75.5 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 76.9 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 76.8 |
AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State
AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol·h/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 183 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 597 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1620 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4330 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4340 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4820 |
AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
AUC (0-tz) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 (NCT00632749)
Timeframe: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
| Intervention | ng·h/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 45.0 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 66.9 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 66.8 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 71.8 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 46.6 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 42.3 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 45.9 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 33.9 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 57.0 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 60.2 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 52.5 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 52.1 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 41.3 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 51.6 |
AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol·h/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 177 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 985 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1000 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 2790 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 4400 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 5620 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 192 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1490 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 2840 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 8870 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 9770 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 14100 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 12800 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 23200 |
AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol·h/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 169 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 939 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 2010 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 2350 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 2810 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 5340 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 156 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1450 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 2730 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 8680 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 9260 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 13700 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 12100 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 21700 |
Cmax (Maximum Measured Concentration of BI 811283 in Plasma)
Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 8.03 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 64.10 |
| 30 mg BI 811283 + 20 mg Cytarabine- Treatment Schedule A | 104.00 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 153.00 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 214.00 |
| 120mg (BI 811283+ Cytarabine)- Treatment Schedule A | 272.00 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 7.06 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 66.10 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 139.00 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 499.00 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 445.00 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 631.00 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 528.00 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1130.00 |
Cmax (Maximum Measured Concentration of Cytarabine in Plasma)
Cmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 (NCT00632749)
Timeframe: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
| Intervention | ng/mL (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 53.2 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 72.6 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 49.0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 64.9 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 61.9 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 46.0 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 46.3 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 49.8 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 55.0 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 65.1 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 49.4 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 48.6 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 49.0 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 68.7 |
Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
Cmax (maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | nmol/L (Geometric Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 8.02 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 24.7 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 43.3 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 141 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 213 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 229 |
Event Free Survival (EFS)
EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first. (NCT00632749)
Timeframe: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
| Intervention | days (Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 35.0 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 122.3 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 32.0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 117.5 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 60.4 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 62.0 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 209.0 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 65.0 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 168.8 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 62.7 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 138.7 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 48.5 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 174.0 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 30.0 |
Incidence of Dose Limiting Toxicity (DLT)
Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD) (NCT00632749)
Timeframe: up to 28 days of treatment
| Intervention | participants (Number) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 2 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
Overall Survival (OS)
OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause. (NCT00632749)
Timeframe: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
| Intervention | days (Mean) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 122.8 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 212.0 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 71.3 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 236.8 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 148.7 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 86.6 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 236.8 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 137.3 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 198.2 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 339.7 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 175.7 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 73.0 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 294.7 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 48.7 |
Partial Remission
"Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria; The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment.~Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or < 5% blasts in the presence of Auer rods or abnormal morphology." (NCT00632749)
Timeframe: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
| Intervention | participants (Number) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 |
Relapse Free Survival
"Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first.~Number of patients having relapse free survival are presented." (NCT00632749)
Timeframe: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
| Intervention | participants (Number) |
|---|
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 2 |
Remission Duration
Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause. (NCT00632749)
Timeframe: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
| Intervention | days (Mean) |
|---|
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 263.0 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 28.0 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 337.0 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 455.0 |
| 240 mg BI 811283+ 20 mg Cytarabine - Treatment Schedule B | 128.0 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 15.0 |
The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine.
"The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only.~It was determined using a standard 3 + 3 design with de-escalation." (NCT00632749)
Timeframe: up to 28 days of treatment
| Intervention | mg (Number) |
|---|
| Treatment Schedule A | 100 |
| Treatment Schedule B | NA |
Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma)
tmax (time from dosing to maximum measured concentration of BI 811283 in plasma) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | hours (Median) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 24.0 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 26.0 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 25.0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 22.7 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 6.0 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 23.6 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 23.9 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 6.0 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 24.1 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 24.9 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 6.0 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 23.9 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 5.9 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 14.8 |
Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma)
Tmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 (NCT00632749)
Timeframe: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
| Intervention | hours (Median) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.50 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.50 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.92 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.83 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.48 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0.55 |
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.50 |
| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.50 |
| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.58 |
| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.50 |
| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.50 |
| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.50 |
| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.48 |
| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0.49 |
Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1 (NCT00632749)
Timeframe: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
| Intervention | hours (Median) |
|---|
| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 23.9 |
| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 24.0 |
| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 6.0 |
| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 6.0 |
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 6.0 |
| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 6.0 |
Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0)
"The severity and timing of AEs indicates how well the treatment regimen was tolerated.~Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme." (NCT00632749)
Timeframe: Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days
| Intervention | participants (Number) |
|---|
| CTCAE Grade 1 | CTCAE Grade 2 | CTCAE Grade 3 | CTCAE Grade 4 | CTCAE Grade 5 |
|---|
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 | 1 | 4 | 2 |
,| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 | 0 | 3 | 4 |
,| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 | 1 | 2 | 0 |
,| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 1 | 1 | 1 |
,| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 2 | 3 | 2 |
,| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 1 | 0 | 2 | 0 |
,| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 1 | 1 | 2 |
,| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 0 | 2 | 1 |
,| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 0 | 2 | 2 |
,| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 0 | 2 | 4 |
,| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 | 1 | 0 | 3 |
,| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 1 | 1 | 2 |
,| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 | 1 | 2 | 1 |
,| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 | 0 | 3 | 2 |
Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi])
"Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria:~The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment.~Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with < 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets > 100,000/μL.~Complete remission with incomplete blood count recovery (incomplete CR, CRi).All of the above criteria for CR had to be met, except that neutrophils < 1,000/μL or platelets < 100,000/μL in the blood." (NCT00632749)
Timeframe: Data collected up to cut-off date 20Oct2011, Up to 1239 days
| Intervention | participants (Number) |
|---|
| CR | CRi |
|---|
| 100 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 |
,| 120 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1 | 0 |
,| 15 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 |
,| 160 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 | 0 |
,| 240 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 | 0 |
,| 30 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 |
,| 300 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 |
,| 360 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 | 1 |
,| 40 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 |
,| 420 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 0 | 0 |
,| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 0 | 0 |
,| 5 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 | 0 |
,| 60 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule A | 1 | 0 |
,| 80 mg BI 811283 + 20 mg Cytarabine - Treatment Schedule B | 1 | 0 |
Event-Free Survival (EFS) at 2 Years
Comparison of the event-free survival (EFS) between treatment CIA and FLAI, where an event is defined to be resistance to treatment, relapse (after response) or death, whichever occurred first. (NCT01289457)
Timeframe: Up to 2 years or until relapse/death
| Intervention | Months (Median) |
|---|
| Group 1 CIA | 7.1 |
| Group 2 FLAI | 8.4 |
Maximum Tolerated Dose (MTD) of Clofarabine, Idarubicin, and Cytarabine
MTD is highest dose level in which <2 patients of 6 develop first cycle dose limiting toxicities (DLT). Toxicity defined as any treatment-related grade 3 or greater non-hematological toxicities. (NCT01289457)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Clofarabine + Idarubicin + Cytarabine | 15 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up. (NCT01289457)
Timeframe: up to 2 years
| Intervention | Months (Median) |
|---|
| Group 1 CIA | 14.5 |
| Group 2 FLAI | 15.1 |
Response Rates of Clofarabine, Idarubicin, and Cytarabine (CIA) Versus Fludarabine, Idarubicin, and Cytarabine (FLAI)
NCI & Myelodysplastic syndromes (MDS) International Working Group (IWG) Definitions: Complete Response (CR): Neutrophil count ≥1.0 ×10^9/L, Platelet count ≥100 ×10^9/L, Bone marrow aspirate 10% after initial response. Response assessed Day 28 of every 2-3 cycles during treatment. (NCT01289457)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 CIA | 107 |
| Group 2 FLAI | 76 |
Event Free Survival
the median time point at which a participants experienced and event or toxicity or progression (NCT00073957)
Timeframe: 12 months
| Intervention | months (Median) |
|---|
| Yttrium Y 90 Ibritumomab | 2.5 |
Best Response
This data is the best overall response achieved by patients by the 12 month period. (NCT00073957)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| CR | PR | SD | PD |
|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | 8 | 1 | 1 | 15 |
Response Rate = Complete and Partial Response at 12 Weeks.
Definition Nodal Masses Spleen, Liver Bone Marrow CR Disappearance of all evidence of disease Partial response Regression and no new sites ≥ 50% decrease in sum of the perpendicular dimension of up to 6 largest dominant masses; no increase in size of other nodes Stable disease Failure to attain CR/PR or Progressive disease or Relapsed disease : the appearance of any new lesion or the (a) FDG-avid or PET positive prior to therapy; PET positive at prior sites of disease and no new sites on CT or PET Any new lesion or increase by ≥ 50% of previously involved sites from nadir Appearance of a new lesion(s) > 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥ 50% increase in longest diameter of a previously identified node > 1 cm in short axis > 50% increase from nadir in the SPD of any previous lesions New or recurrent involvement Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy (NCT00073957)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | 5 | 3 | 2 | 15 |
Overall Survival
Overall Survival at six years after initiating protocol therapy (NCT00083551)
Timeframe: 6 Years
| Intervention | percentage of participants (Number) |
|---|
| Thalidomide | 65 |
| No Thalidomide | 58 |
Overall Survival (OS)
OS is measured from the start of on-study to the date of death or to the last date of follow-up. Measurement is determined by Kaplan-Meyer estimate. The probability of survival at 5 years after diagnosis is given. (NCT00186875)
Timeframe: 2 years after last patient completes therapy (approximately 4 years after enrollment)
| Intervention | probability (Mean) |
|---|
| Standard Risk | 0.654 |
| High Risk | 0.357 |
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111)
The prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL. MRD is considered as positive (i.e., prevalent) if its level is >=0.01%. The prevalence of MRD after Block B is defined as the proportion of MRD positives. (NCT00186875)
Timeframe: End of Block B therapy (Day 19)
| Intervention | Participants (Count of Participants) |
|---|
| Negative <0.01% | Positive ≥0.01% |
|---|
| High Risk | 2 | 10 |
,| Standard Risk | 11 | 11 |
,| TOTXV Participants | 191 | 297 |
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111)
The prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL. MRD is considered as positive (i.e., prevalent) if its level is >=0.01%. The prevalence of MRD after Block C is defined as the proportion of MRD positives. (NCT00186875)
Timeframe: End of Block Block C therapy (Day 46)
| Intervention | Participants (Count of Participants) |
|---|
| Negative <0.01% | Positive ≥0.01% |
|---|
| High Risk | 1 | 8 |
,| Standard Risk | 11 | 9 |
,| TOTXV Participants | 390 | 102 |
Response Rate
"The response rate is defined as the proportion of participants who attain morphological complete remission after the re-induction Block C, inclusive of all patients who begin re-induction. Morphological complete remission was defined as <5% blasts in bone marrow by morphology." (NCT00186875)
Timeframe: End of re-induction Block C (approximately 1 month after the start of therapy)
| Intervention | proportion of participants (Number) |
|---|
| Complete remission | Failure to reach complete remission |
|---|
| High Risk | 0.786 | 0.214 |
,| Standard Risk | 0.846 | 0.154 |
Number of Participants With Complete Response (CR)
Complete Response Criteria (CR must last for at least 4 weeks): Marrow: /= 11 g/dL (untransfused, patient not on EPO); Neutrophils >/= 1x109/L (not on myeloid growth factor); Platelets >/= 100 * 109/L (not on thrombopoietic agent); No blasts. Bone marrow aspirate and/or biopsy at the end of course 1 (day 28 +/- 7 days). The method of Thall, Simon, and Estey used to monitor response. (NCT01444742)
Timeframe: 4 weeks after first cycle
| Intervention | Participants (Count of Participants) |
|---|
| Clofarabine + Cytarabine | 19 |
Overall Survival (OS)
Overall survival defined as the time interval from study entry date to the date of death due to any cause, measured in days/months. Bayesian time-to-event model used to monitor overall survival. (NCT01444742)
Timeframe: 5 years
| Intervention | Months (Median) |
|---|
| Clofarabine + Cytarabine | 10.3 |
Disease-free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse. (NCT01692197)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| E7070 + Idarubicin + Cytarabine | 1.7 |
Duration of Response
Response date to loss of response or last follow up. (NCT01692197)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| E7070 and Idarubicin and Cytarabine | 6.7 |
Overall Response
Efficacy measured by overall response - complete response plus complete response with incomplete platelet recovery, plus partial response (Complete remission (CR) + Complete remission without platelet recovery (CRp) + Partial Remission (PR)+ marrow clearance of blast) during cycle 1. (NCT01692197)
Timeframe: 2 cycles (60 days)
| Intervention | Participants (Count of Participants) |
|---|
| E7070 and Idarubicin and Cytarabine | 11 |
Overall Survival
Time from date of treatment start until date of death due to any cause or last follow-up. (NCT01692197)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| E7070 and Idarubicin and Cytarabine | 5.1 |
Procedure or Procedure Related Adverse Events
Number of unique patients who had a procedure or treatment related (possible, probable or definite) adverse events. (graded per NCI CTC v4.0) (NCT02485353)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Vosaroxin and Cytarabine | 1 |
Rate of Complete Remission
Percentage of patients who have complete remission as defined by the International Working Group for AML: morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi or CRp) (NCT02485353)
Timeframe: 2 months
| Intervention | percentage of patients (Number) |
|---|
| Vosaroxin and Cytarabine | 0 |
Duration of Exposure of Entospletinib
(NCT02343939)
Timeframe: First dose date up to approximately 3 years
| Intervention | weeks (Median) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 8.6 |
| Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin | 7.1 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 13.7 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 15.4 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 10.1 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 13.9 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 10.1 |
| Group C Phase 1b/2 ENTO 400 mg | 4.4 |
| Group C Phase 1b ENTO 800 mg | 7.6 |
Event Free Survival (EFS)
EFS was defined as the time interval from the start of the study therapy until the date of treatment failure, acute myeloid leukemia (AML) relapse, or death from any cause, whichever occurred first. Participants who received other anti-cancer therapy (prior to the event if any) were censored. Median EFS was analyzed using Kaplan-Meier (KM) method. (NCT02343939)
Timeframe: First dose date up to approximately 38 months
| Intervention | months (Median) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | NA |
| Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin | 1.9 |
| Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin | 9.0 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 2.2 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 2.9 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 2.3 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 3.2 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 2.4 |
| Group C Phase 1b ENTO 400 mg | 1.8 |
| Group C Phase 1b ENTO 800 mg | 1.8 |
| Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) | 1.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) | 1.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) | 1.7 |
Overall Survival (OS)
OS was defined as the time interval from the start of the study therapy to death from any cause. Median OS was analyzed using KM method. (NCT02343939)
Timeframe: First dose date up to approximately 38 months
| Intervention | months (Median) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 37.1 |
| Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin | 34.1 |
| Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin | NA |
| Group B Phase 1b ENTO 200 mg + Decitabine | 3.2 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 5.3 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 6.9 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 7.3 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 6.2 |
| Group C Phase 1b ENTO 400 mg | 5.9 |
| Group C Phase 1b ENTO 800 mg | 5.6 |
| Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) | 8.2 |
| Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) | 7.9 |
| Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) | 2.2 |
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLT assessment was applicable only for Phase 1b and Phase 2 safety run-in participants. (NCT02343939)
Timeframe: Group A: Cycle 0 Day 1 to Cycle 2 Day 28; Group B: Cycle 0 Day 1 to Cycle 1 Day 28; Group C: Cycle 1 Day 1 to Cycle 1 Day 28 (Cycle length: for Cycle 0 = 14 days, for all other cycles = 28 days)
| Intervention | percentage of participants (Number) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 0 |
| Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin | 0 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 0 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 16.7 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 0 |
| Group C Phase 1b/2 ENTO 400 mg | 0 |
| Group C Phase 1b ENTO 800 mg | 16.7 |
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
(NCT02343939)
Timeframe: First dose date up to the last dose date plus 30 days (maximum: 18 months)
| Intervention | percentage of participants (Number) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 100.0 |
| Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin | 100.0 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 100.0 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 100.0 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 100.0 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 100.0 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 100.0 |
| Group C Phase 1b/2 ENTO 400 mg | 100.0 |
| Group C Phase 1b ENTO 800 mg | 100.0 |
Percentage of Participants With Composite Complete Remission at the End of Induction
Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Composite complete remission included CR, CRc, and morphologic complete remission with incomplete blood count recovery (CRi). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets. (NCT02343939)
Timeframe: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 100.0 |
| Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin | 77.8 |
| Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin | 65.9 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 40.0 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 50.0 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 25.0 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 23.5 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 14.3 |
| Group C Phase 1b ENTO 400 mg | 14.3 |
| Group C Phase 1b ENTO 800 mg | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) | 15.4 |
| Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) | 11.1 |
Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction
Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Morphologic CR included CR and cytogenetic CR (CRc). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/microliter (mcL); Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. (NCT02343939)
Timeframe: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 66.7 |
| Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin | 66.7 |
| Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin | 46.3 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 0.0 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 16.7 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 25.0 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 0.0 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 7.1 |
| Group C Phase 1b ENTO 400 mg | 0.0 |
| Group C Phase 1b ENTO 800 mg | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) | 15.4 |
| Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) | 11.1 |
Percentage of Participants With Overall Response at the End of Induction
Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Overall response included CR, CRc, CRi, and partial remission (PR). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets. PR required all of the following: ≥ 50% decrease in blasts in bone marrow aspirate to a range of 5% to 25%; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; Independent of transfusions; and A value of ≤ 5% blasts was also considered a PR if Auer rods were detected. (NCT02343939)
Timeframe: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 100.0 |
| Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin | 77.8 |
| Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin | 70.7 |
| Group B Phase 1b ENTO 200 mg + Decitabine | 40.0 |
| Group B Phase 1b ENTO 400 mg + Decitabine | 50.0 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 25.0 |
| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 23.5 |
| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 14.3 |
| Group C Phase 1b ENTO 400 mg | 14.3 |
| Group C Phase 1b ENTO 800 mg | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) | 0.0 |
| Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) | 15.4 |
| Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) | 11.1 |
Percentage of Participants Who Experienced Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. (NCT02343939)
Timeframe: First dose date up to the last dose date plus 30 days (maximum: 18 months)
| Intervention | percentage of participants (Number) |
|---|
| Any Laboratory Abnormality | Grade 3 or 4 Laboratory Abnormalities |
|---|
| Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin | 100 | 100 |
,| Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin | 100 | 98.0 |
,| Group B Phase 1b ENTO 200 mg + Decitabine | 100 | 100 |
,| Group B Phase 1b ENTO 400 mg + Decitabine | 100 | 100 |
,| Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) | 100 | 92.9 |
,| Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) | 100 | 85.7 |
,| Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) | 94.1 | 94.1 |
,| Group C Phase 1b ENTO 800 mg | 100 | 85.7 |
,| Group C Phase 1b/2 ENTO 400 mg | 100 | 82.9 |
Complete Remission Rate
Complete remission rate is defined as number of subjects with complete remission according to the IWG criteria, which is defined by presence of <5 percent of blasts in the bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count >1.0 x 109/L (1000/µL); platelet count >100 x 109/L (100,000/µL); independence of red cell transfusions. (NCT02532010)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Pacritinib and Decitiabine | 0 |
| Arm B: Pacritinib and Cytarabine | 0 |
Event-free Survival
Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause (NCT02532010)
Timeframe: Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause, assessed throughout the study period up to 2 years
| Intervention | months (Median) |
|---|
| Arm A: Pacritinib and Decitiabine | 2.5 |
| Arm B: Pacritinib and Cytarabine | 3 |
Overall Remission Rate
Overall remission rate is defined as number of subjects with complete remission (CR), Complete Remission with incomplete platelet recovery (CRp), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) according to the IWG criteria. CRi is defined as All CR criteria except for residual neutropenia (<1.0 x 109/L (1000/µL)) or thrombocytopenia (<100 x 109/L (100,000/µL)), PR is defined as relevant in the setting of phase I and II clinical trials only; all hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pretreatment bone marrow blast percentage by at least 50 percent. (NCT02532010)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Pacritinib and Decitiabine | 0 |
| Arm B: Pacritinib and Cytarabine | 0 |
Overall Survival
Survival following treatment to the date of death (NCT02532010)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Pacritinib and Decitiabine | 3 |
| Arm B: Pacritinib and Cytarabine | 3 |
Relapse-free Survival
Time from complete remission documentation to either AML relapse or death from any cause. (NCT02532010)
Timeframe: From date of complete remission until either AML relapse or death from any cause, whichever came first, assessed throughout the study period up to 2 years
| Intervention | months (Median) |
|---|
| Arm A: Pacritinib and Decitiabine | NA |
| Arm B: Pacritinib and Cytarabine | NA |
Remission Duration
Time from CR documentation to AML relapse (NCT02532010)
Timeframe: time from complete remission to AML relapse, assessed throughout the study period up to 2 years.
| Intervention | months (Median) |
|---|
| Arm A: Pacritinib and Decitiabine | NA |
| Arm B: Pacritinib and Cytarabine | NA |
Time to Complete Response
Time from entry on study until documentation of complete remission (CR) (NCT02532010)
Timeframe: From entry on study until complete remission, assessed throughout the study period up to 2 years
| Intervention | months (Median) |
|---|
| Arm A: Pacritinib and Decitiabine | NA |
| Arm B: Pacritinib and Cytarabine | NA |
Level of Methylation
the percentage of methylated DNA (NCT00882206)
Timeframe: Day 0
| Intervention | percentage of DNA (Mean) |
|---|
| Decitabine / Vorinostat | 84.98 |
Level of Methylation
the percentage of methylated DNA (NCT00882206)
Timeframe: Day 33
| Intervention | percentage of DNA (Mean) |
|---|
| Decitabine / Vorinostat | 86.1 |
Level of Methylation
the percentage of methylated DNA (NCT00882206)
Timeframe: Day 5
| Intervention | percentage of DNA (Mean) |
|---|
| Decitabine / Vorinostat | 79.82 |
Response to Treatment
Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33) (NCT00882206)
Timeframe: Day 33
| Intervention | participants (Number) |
|---|
| Decitabine / Vorinostat | 6 |
Event-free Survival (EFS)
EFS was measured from the date of randomisation to the date of progression or relapse, or death from any cause, whichever occurred first. (NCT01721876)
Timeframe: From randomization until disease progression or relapse or death from any cause, up to 1557 days.
| Intervention | Months (Median) |
|---|
| Placebo + Low-dose Cytarabine | 2.8 |
| Volasertib + Low-dose Cytarabine | 3.3 |
Objective Response (OR)
OR is the number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi), where OR was based on the best response attained during the treatment period. (NCT01721876)
Timeframe: Response assessment was performed at the end of every 2nd cycle, (i.e. at the end of Cycle 2, 4, 6, 8, etc., and at end of treatment), i.e. up to 52 months.
| Intervention | Participants (Number) |
|---|
| Placebo + Low-dose Cytarabine | 38 |
| Volasertib + Low-dose Cytarabine | 123 |
Overall Survival (OS)
OS is the key secondary endpoint and was measured from the date of randomization until death from any cause. Patients who were lost to follow-up were censored on the last date they were known to be alive. (NCT01721876)
Timeframe: From randomization until death due to any cause, up to 1557 days.
| Intervention | Months (Median) |
|---|
| Placebo + Low-dose Cytarabine | 6.5 |
| Volasertib + Low-dose Cytarabine | 5.6 |
Relapse-free Survival (RFS)
RFS was defined only for patients who achieved best overall response of CR or CRi; it was measured from the date of achievement of a remission until the date of relapse or death from any cause. Patients not known to have relapsed or died at last follow-up were censored on the date they were last examined. (NCT01721876)
Timeframe: From randomization until disease progression or relapse or death from any cause, up to 1557 days.
| Intervention | Months (Median) |
|---|
| Placebo + Low-dose Cytarabine | 18.7 |
| Volasertib + Low-dose Cytarabine | 13.1 |
Event-free Survival
Event-free survival (EFS) was defined as the time for registration to failure to achieve CR during induction, relapse or death. Participants without events were censored at date of last follow-up. The median EFS with 95% CI was estimated using the Kaplan Meier method. (NCT01253070)
Timeframe: Time from registration to death or relapse (up to 10 years)
| Intervention | months (Median) |
|---|
| ITD Mutated Participants | 8.8 |
| TKD Mutated Participants | 7.8 |
OS
OS was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method. (NCT01253070)
Timeframe: Time from registration to death (up to 10 years)
| Intervention | months (Median) |
|---|
| ITD Mutated Participants | 15 |
| TKD Mutated Participants | 16.2 |
Overall Survival (OS) Rate
Percentage of patients who were alive at 1 year. The analysis was split between patients with having a FLT3 (FMS-like tyrosine kinase-3) ITD (internal tandem duplication) or TKD (tyrosine kinase domain) mutation. The FLT3 mutation testing at baseline was performed centrally for all patients. (NCT01253070)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| ITD Mutated Participants | 62 |
| TKD Mutated Participants | 71 |
Disease-Free Survival Rate at 2-year and 5-year.
Disease-Free Survival (DFS) was calculated from the time of complete remission until relapse or death due to any cause. (NCT00038610)
Timeframe: Baseline to 2-year and 5-year
| Intervention | percentage of participants (Number) |
|---|
| 2-year DFS rate | 5-year DFS rate |
|---|
| Hyper-CVAD + Imatinib | 49 | 43 |
Overall Survival Rate at 2-year and 5-year.
Overall survival (OS) was calculated from the date of initiation of therapy until death. (NCT00038610)
Timeframe: Baseline to 2-year and 5-year
| Intervention | percentage of participants (Number) |
|---|
| 2-year OS rate | 5-year OS rate |
|---|
| Hyper-CVAD + Imatinib | 57 | 43 |
Response To Induction Therapy With Hyper-CVAD Plus Imatinib Mesylate
"Complete Remission (CR): Defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count of 1.0 × 109/L or higher and a platelet count of 100 × 109/L and no extramedullary disease.~Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts.~Molecular CR: Same as for CR with RT-PCR negativity for bcr-abl.~Induction Death: Defined as death occurring after start of therapy without meeting the definition of CR or resistant disease." (NCT00038610)
Timeframe: Baseline to 6 months
| Intervention | participants (Number) |
|---|
| Complete Remission | Partial Remission | Molecular Complete Remission | Induction Death |
|---|
| Hyper-CVAD + Imatinib | 42 | 1 | 17 | 1 |
Number of Participants With Response
"Participant responses are categorized as 'Complete Remission,' Complete Remission, No Platelet Recovery,' 'No Response.'~Complete Remission: Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x 109/L and platelet count > 100 x 109/L, and normal bone marrow differential (< 5% blasts); Complete Remission, No Platelet Recovery: Peripheral blood and bone marrow results as for CR, but with platelet counts of < 100 x 109/L.~Blood draws once a week until remission then every 2 to 8 weeks during therapy." (NCT00088218)
Timeframe: Every 2 to 8 weeks
| Intervention | Participants (Number) |
|---|
| Complete Remission | Complete Remission, No Platelet Recovery | No Response |
|---|
| Clofarabine | 5 | 0 | 11 |
,| Clofarabine Plus Ara-C | 49 | 4 | 26 |
Number of Participants Who Had an Adverse Event While on Treatment With Clofarabine Plus Cytarabine
Patients will be monitored clinically and diagnostically using measures including blood test, bone marrow aspiration and MUGA. Toxicity assessment every week using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be performed. (NCT00334074)
Timeframe: Up to five months (includes follow up period of 30 days) from the day patient received their first dose of study drug
| Intervention | participants; with adverse events (Number) |
|---|
| Clofarabine and Cytarabine | 30 |
Response Rate (Complete Response [CR] Plus Partial Response [PR]) of Clofarabine Plus Cytarabine in Patients With Relapsed/Refractory AML, Untreated MDS, CML in Blast Phase, or in Selected Untreated Patients With High Risk of Anthracycline Toxicity
"Based on International working group for diagnosis, standardization of response criteria, and treatment outcomes for reporting standards for therapeutic trials in Acute myeloid Leukemia:~Complete Response (CR) was defined as normalization of marrow blasts (< 5%), recovery of normal heamtopoiesis (absolute neutrophil count >1 X 10^9/l, platelet count ≥100 X10^9/l, and absence of peripheral blood blasts, independent of transfusions and growth factor support.~Partial response was defined as blood count recovery as for complete response with the exception of leukemic marrow blasts in the range of 6%-25% or a ≥50% decrease in bone marrow blasts.~Treatment failure was defined as a <25% change in marrow blasts within 30 days of starting therapy" (NCT00334074)
Timeframe: Proportion of confirmed responses was estimated by the number of patients who achieved a CR or PR, defined as two consecutive evaluations at least 4 weeks apart, divided by the number of eligible participants in the study.
| Intervention | participants (Number) |
|---|
| Overall Response Rate | Complete Response | Partial Response | Not Responding | Not evaluable |
|---|
| Clofarabine Plus Cytarabine | 16 | 14 | 2 | 8 | 6 |
Duration of Remission
With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. Remission is defined as less than 5% blasts in the bone marrow, no appearance of blasts in the peripheral blood, and no extramedullary disease (appearance of leukemic cells in other tissues). (NCT01101880)
Timeframe: Up to 5 years
| Intervention | weeks (Median) |
|---|
| Treatment (Chemotherapy and Colony Stimulating Factor) | 7 |
Event Free Survival
Number of patients in remission at a median follow up of 15 months. (NCT01101880)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy and Colony Stimulating Factor) | 21 |
Overall Survival
With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. (NCT01101880)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Treatment (Chemotherapy and Colony Stimulating Factor) | 24.3 |
Time to Progression
With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. (NCT01101880)
Timeframe: Up to 5 years
| Intervention | weeks (Median) |
|---|
| Treatment (Chemotherapy and Colony Stimulating Factor) | 7 |
Rates of Complete Remission and Complete Remission With Incomplete Recovery of Counts
With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. Complete remission is defined as less than 5% blast cells present in the bone marrow and count recovery (absolute neutrophil count greater than 1000/microL and platelet count greater than 100,000/microL). Complete remission with incomplete recovery of counts is defined as less than 5% blast cells present in the bone marrow without compete count recovery (absolute neutrophil count less than 1000/microL and platelet count less than 100,000/microL). (NCT01101880)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| CR achieved | CR achieved with first course of induction | CR + CRp achieved | CR achieved with no AHD | CR achieved with AHD | CR + CRp achieved with AHD | CR achieved with FLT3 positive | CR achieved with favorable risk cytogenetics | CR achieved with intermediate risk cytogenetics | CR + CRp achieved with intermediate risk cyto. | CR achieved with unfavorable risk cytogenetics | CR + CRp achieved with unfavorable risk cyto. |
|---|
| Treatment (Chemotherapy and Colony Stimulating Factor) | 38 | 33 | 41 | 23 | 15 | 18 | 7 | 4 | 26 | 27 | 8 | 10 |
Complete Response Rate
"Proportion of patients who have achieve CR or CRp after treatment.~Morphologic Complete Remission (CR): Defined as morphologic leukemia-free state, including <5% blasts in Bone Marrow aspirate with marrow spicules, no persistent extramedullary disease, ANC >1000/mm3 and platelet count >100,000/mm3.~Morphologic Complete Remission without platelet recovery (CRp): Defined as CR with the exception of platelet count < 100,000/mm3 (CRp)." (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 19 |
Number of Patients That Achieved ANC Recovery
The number of patients that achieved a neutrophil count of > 500/mm3 for 3 days within 45 of starting treatment (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 25 |
Number of Patients That Achieved Platelet Recovery
The number of patients that achieved a stable platelet count > 20,000/mm3 for 3 days within 45 days of starting treatment (NCT03118466)
Timeframe: up to 45 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 27 |
Overall Survival
Overall survival is defined as time from diagnosis of disease until date of death or censored on the last known date alive if patients are still alive. (NCT03118466)
Timeframe: Up to 3 years
| Intervention | Months (Median) |
|---|
| Lenalidomide and MEC Chemotherapy | 16 |
Treatment-related Mortality
Cumulative number of deaths not related to persistent or relapsed leukemia during treatment within 50 days of the start of treatment. (NCT03118466)
Timeframe: 50 days
| Intervention | Participants (Count of Participants) |
|---|
| Lenalidomide and MEC Chemotherapy | 2 |
Transfusion Support: Number of Red Blood Cell and Platelet Transfusions
Number of red blood cell and platelet transfusions received within the first 50 days of treatment (NCT03118466)
Timeframe: 50 days
| Intervention | Number of Transfusions (Median) |
|---|
| Platelet Transfusions | Red Blood Cell Transfusions |
|---|
| Lenalidomide and MEC Chemotherapy | 7 | 9 |
Antitumor Activity of Flotetuzumab
Number of response evaluable participants with response (CR/PR) using revised AML International Working Group criteria for response including CR: M1 bone marrow (<5% blasts), ANC at least 1000/mm3 and platelet count at least 100,000/mm3; CRp: platelet transfusion independence; CRi: without platelet transfusion independence, CRc: revision to normal karyotype; PR: decrease at least 50% in percentage of blasts to 5% to 25% in bone marrow aspirate. (NCT04158739)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Part A Dose Level 1:500 Nanograms/kg/Day | 1 |
| Part A Dose Level 2: 700 Nanograms/kg/Day | 1 |
Dose Limiting Toxicities Due to Flotetuzumab
Number and percentage of patients experiencing dose limiting toxicities during cycle 1 that are possibly, probably, or definitely due to flotetuzumab by dose level and study part. (NCT04158739)
Timeframe: Up to 29 days
| Intervention | Participants (Count of Participants) |
|---|
| Part A Dose Level 1: 500 Nanograms/kg/Day | 1 |
| Part A Dose Level 2: 700 Nanograms/kg/Day | 1 |
Maximum Concentration (C Max)
Median with Minimum and Maximum for the maximum (peak) serum concentration measured on days 3-9 post-administration by dose level and study part. (NCT04158739)
Timeframe: Up to 9 days
| Intervention | pg/ml (Median) |
|---|
| Part A Dose Level 1: 500 Nanograms/kg/Day | 108.6 |
| Part A Dose Level 2: 700 Nanograms/kg/Day | 147.6 |
Maximum Tolerated Dose or Recommended Phase 2 Dose of Flotetuzumab
Estimated maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of Flotetuzumab defined by the maximum dose at which fewer than one-third of toxicity-evaluable participants experience a DLT. RP2D was established by study committee based off the toxicity profile of DL1 (500 ng/kg/day). (NCT04158739)
Timeframe: Up to 29 days
| Intervention | nanograms/kg/day (Number) |
|---|
| Treatment (Flotetuzumab, Cytarabine) | 500 |
Duration of Disease Control Rate
Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks. (NCT02088541)
Timeframe: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
| Intervention | Days (Median) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 187.0 |
| Physician's Choice 2 (PV >=5) | 233.0 |
Duration of Response (DOR)
DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Days (Median) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 204.0 |
| Physician's Choice 2 (PV >=5) | 148.0 |
Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Days (Median) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 121.0 |
Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission or CR With Incomplete Hematologic Recovery (CRi) or Complete Remission With Incomplete Platelet Recovery (CRp)
DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Days (Median) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 175.0 |
| Physician's Choice 2 (PV >=5) | 106.0 |
Overall Survival
Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Days (Median) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 94.0 |
| Physician's Choice 2 (PV >=5) | 170.0 |
Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 5.1 |
| Physician's Choice 2 (PV >=5) | 0 |
Percentage of Participants With Disease Control Rate (DCR)
DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks. (NCT02088541)
Timeframe: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
| Intervention | Percentage of participants (Number) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 50.8 |
| Physician's Choice 2 (PV >=5) | 40.4 |
Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 11.9 |
| Physician's Choice 2 (PV >=5) | 3.5 |
Percentage of Participants With Overall Response Rate (ORR)
Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required. (NCT02088541)
Timeframe: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 13.6 |
| Physician's Choice 2 (PV >=5) | 8.8 |
Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. (NCT02088541)
Timeframe: From randomization (Day 1) up to 3 months
| Intervention | Percentage of participants (Number) |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 53.49 |
| Physician's Choice 2 (PV >=5) | 70.73 |
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state. (NCT02088541)
Timeframe: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | C2D1 | C3D1 | C4D1 | C5D1 | C6D1 | C7D1 | C8D1 | C9D1 | C10D1 | C11D1 | C12D1 | C13D1 | C14D1 | C15D1 | C16D1 | C17D1 |
|---|
| Physician's Choice 2 (PV >=5) | 63.5 | 0.8 | -5.2 | -5.0 | -2.0 | -1.4 | 4.0 | 5.0 | 5.0 | 6.3 | -5.0 | -5.0 | 10.0 | 15.0 | -10.0 | 20.0 | -5.0 |
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state. (NCT02088541)
Timeframe: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | C2D1 | C3D1 | C4D1 | C5D1 | C6D1 | C7D1 | C8D1 | C9D1 | C10D1 | C11D1 | C12D1 | C13D1 | C14D1 | C15D1 | C17D1 | C18D1 | C19D1 | C20D1 |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 67.9 | -7.5 | -13.3 | -6.1 | -0.9 | -11.2 | -3.7 | 0.1 | 4.6 | 0.7 | 0.8 | 3.3 | 6.7 | 6.7 | 3.5 | 25.0 | 25.0 | 30.0 | 35.0 |
Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit. (NCT02088541)
Timeframe: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | C2D1 | C3D1 | C4D1 | C5D1 | C6D1 | C7D1 | C8D1 | C9D1 | C10D1 | C11D1 | C12D1 | C13D1 | C14D1 | C15D1 | C16D1 | C17D1 | Final visit |
|---|
| Physician's Choice 2 (PV >=5) | 75.4 | -1.9 | -5.4 | -7.4 | 1.9 | -4.7 | -11.8 | -10.6 | -8.0 | -10.7 | -10.0 | -7.0 | -9.0 | -15.0 | -10.0 | -15.0 | -7.0 | -1.7 |
Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit. (NCT02088541)
Timeframe: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
| Intervention | Units on a scale (Mean) |
|---|
| Baseline | C2D1 | C3D1 | C4D1 | C5D1 | C6D1 | C7D1 | C8D1 | C9D1 | C10D1 | C11D1 | C12D1 | C13D1 | C14D1 | C15D1 | C17D1 | C18D1 | C19D1 | C20D1 | Final visit |
|---|
| Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) | 70.5 | 0.5 | -1.9 | -1.2 | -2.4 | -3.4 | -5.0 | -3.9 | -2.7 | 2.4 | -0.1 | -3.7 | -3.3 | -4.0 | 1.5 | -15.0 | -1.0 | -12.0 | -14.0 | 2.5 |
Early Death Rate
Early death was defined as death before the end of the first induction cycle. (NCT02249091)
Timeframe: 1 induction cycle (4 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 0 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 4 |
Event-Free Survival
Event-free survival (EFS) was calculated from the time of informed consent until death, not achieving CR/CRi or relapse after CR/CRi. (NCT02249091)
Timeframe: Time from registration to event, max 2 years
| Intervention | months (Median) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 5.6 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 4.3 |
Number of Participants With CR/CRi = Overall Reponse Rate
"Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of complete response (CR) or morphologic complete response with incomplete blood count recovery (CRi), as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:~CR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.~CRi: Same as CR, but ANC may be <1.0x10^9/L and/or Platelet count <100x10^9/L.~Patients with morphologic leukemia free-state (MLFS) were included in the group of responders. MLFS: Bone marrow blasts <5%, no Auer rods, no evidence of extramedullary disease.~The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s)." (NCT02249091)
Timeframe: 1-2 induction cycles (4 - 8 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 15 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 6 |
Number of Participants With Partial Remission (PR) = Rate of PR
"Efficacy of selinexor in combination with standard chemotherapy in patients with relapsed/refractory AML by determination of rate of partial remission(PR) as defined by the recommendations on diagnosis and management of AML in adults from an international expert panel, on behalf of the European LeukemiaNet:~PR: Absolute Neutrophil count (ANC) >1.0x10^9/L, Platelet count >100x10^9/L, at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts <5% with persistent Auer rods.~The best response after Selinexor treatment was analyzed, thus the best response after the induction cycle(s)." (NCT02249091)
Timeframe: 1-2 induction cycles (4 - 8 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 0 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 0 |
Overall Survival
Overall survival (OS) was calculated from the date of informed consent to the date of death. Patients still alive at the end of follow-up were censored at the last date of follow-up. (NCT02249091)
Timeframe: Time from registration to event, max 2 years
| Intervention | months (Median) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 12.6 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 8.0 |
Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)
Percentage of patients being transplanted after induction therapy (stem cell transplantation) (NCT02249091)
Timeframe: 1-2 induction cycles (4 - 8 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 11 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 4 |
Progression-Free Survival
"Progression-free survival (PFS) was calculated from the time of informed consent to the date of recurrence or death, whichever occurred first. Patients were censored at the date of the last follow-up visit if they were alive without relapse.~Disease progression was defined as presence of >50% increase in bone marrow blasts to a level of at least 50% and/or a doubling of the percentage of peripheral blood blasts to a level of at least 50%." (NCT02249091)
Timeframe: Time from registration to event, max 2 years
| Intervention | months (Median) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 6.3 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | 4.3 |
Relapse-Free Survival
Relapse-free survival (RFS) was calculated from the date of CR/CRi until death or relapse, whichever occurred first. Patients were censored on the date of the last follow-up if they were alive without relapse. (NCT02249091)
Timeframe: Time from registration to event, max 2 years
| Intervention | months (Median) |
|---|
| Cohort 1 / Selinexor 40 mg/m^2 in Combination With Cytarabine and Idarubicin | 10.9 |
| Cohort 2 / Selinexor 60 mg Flat Dose in Combination With Cytarabine and Idarubicin | NA |
Complete Response (CR) Rate in Patients With Relapsed or Refractory AML
"Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group (IWG) Criteria and 2010 European LeukemiaNet (EN) criteria in patients with relapsed or refractory AML with MCL-1 dependence >30% and in Stage 2 by the 2017 ELN criteria.~The study was terminated in January 2020 due to a steady and marked reduction in enrollment. Thus, the efficacy endpoints could not be analyzed. As sufficient efficacy results were not available to analyze patients based on the percentage of MCL-1 dependency the treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received the ACM vs CM regimen and their disease stages at study entry." (NCT02520011)
Timeframe: Best response after at least 1 cycle through study completion approximately 4 years
| Intervention | participants (Number) |
|---|
| Complete Remission (CR) | CR with Incomplete Neutrophil Recovery (Cri) | Partial Remission (PR) | Resistant/Relapsed Disease | Not Evaluated |
|---|
| All Stages and Cohorts (Including Randomized Stage): ACM Total | 27 | 17 | 2 | 34 | 13 |
,| Stage 1 ACM Relapsed/Refractory | 8 | 5 | 1 | 5 | 6 |
,| Stage 1 Newly Diagnosed ACM | 6 | 2 | 1 | 4 | 1 |
,| Stage 2 ACM Relapsed/Refractory | 2 | 3 | 0 | 5 | 1 |
,| Stage 2 CM Relapsed/Refractory | 6 | 0 | 0 | 5 | 0 |
,| Stages 1 and 2 ACM Relapsed/Refractory | 21 | 15 | 1 | 30 | 12 |
Response to Treatment
To determine if treatment with ACM can induce CR in patients with relapsed or refractory AML with MCL-1 dependence of >30% who failed to achieve CR following 1 cycle of CM (NCT02520011)
Timeframe: Best response after at least 1 cycle through study completion approximately 4 years
| Intervention | participants (Number) |
|---|
| Partial Remission (PR) | Not Evaluated |
|---|
| Stage 2 CM Relapsed/Refractory AML | 1 | 1 |
Evaluate Toxicity by Assessing the Adverse Events of Metformin and Cytarabine
To determine the maximum tolerated dose (MTD) by assessing the adverse events of metformin in combination with cytarabine in evaluating toxicity. Assessments will occur daily during cytarabine administration and at least twice weekly following treatment until blood count recovery. (NCT01849276)
Timeframe: Checked daily during administration of cytarabine and at least 2x weekly following therapy until desired blood counts acheived (maximum 15 days)
| Intervention | Adverse events related to treatment (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Treatment (Enzyme Inhibitor and Chemotherapy) | 4 | 6 | 2 | 0 |
Event Free Survival (EFS)
Event free survival defined as the time from treatment to relapse of leukemia or death for any reason or lost to follow-up. Study regimen considered successful if it exhibits a 3-year EFS rate greater than 65% and response rate no less than 90% with Grade III-IV infectious toxicity rate in induction no more than 33%. (NCT02419469)
Timeframe: 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Ofatumumab Plus Chemotherapy | NA |
Complete Response (CR)
"Complete response (CR) was determined the number of participants who achieved CR by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. CR is defined as:~CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.~Not CR = All statuses and conditions if less than or not as defined." (NCT01769209)
Timeframe: Day 29
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 11 |
Complete Response Without Platelet Recovery (CRp)
"Complete response without platelet recovery (CR) was determined as the number of participants who achieved CRp by Day 29 after induction treatment. The outcome is reported as the total number without dispersion. The outcome reflects only those subjects that meet all complete response (CR) criteria except platelet count; participants that meet all criteria including platelet count are not included in this outcome. CR and CRp are defined below.~CR =.No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.~CRp = Meets all criteria for CR except platelet count." (NCT01769209)
Timeframe: Day 29
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 1 |
Failure-free Survival (FFS)
"Failure-free survival (FFS) was assessed as survival without progression or the addition of another systemic therapy, at or within 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression. Progression is defined below.~Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease." (NCT01769209)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 3 |
Overall Survival (OS)
Overall survival (OS) was assessed as participants remaining alive 2 years after induction therapy. The outcome is reported as the number of participants (without dispersion). (NCT01769209)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 5 |
Progression-free Survival (PFS)
"Progression-free survival (PFS) was assessed as survival without progression at 2 years. The outcome is reported as the number (without dispersion) of the participants alive without progression.~Progression = More than 25% increase in circulating and/or bone marrow blasts, or the development of extramedullary disease." (NCT01769209)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 3 |
Response Rate (RR)
"Response Rate (RR) was determined as the sum of complete response (CR) and partial response (PR). Due to overlap, complete response rate without platelet recovery (CRp) is not included in Response Rate (RR). The outcome is reported as the total number without dispersion.~CR = No circulating blasts or extramedullary disease; trilineage hematopoiesis; absolute neutrophil count (ANC) > 1,000/microliter; platelets > 100,000/microliter; < 5% blasts in bone marrow.~CRp = Meets all criteria for CR except platelet count.~PR = Meets all criteria for CR except bone marrow contains 5 to 25% leukemia cells." (NCT01769209)
Timeframe: Day 29
| Intervention | Participants (Count of Participants) |
|---|
| Bortezomib + Chemotherapy | 11 |
Related Adverse Events (Grade 3, 4, 5)
Toxicity was assessed as related grade 3, 4, or 5 adverse events (AEs) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The outcome is reported as the total numbers of events (without dispersion) by CTCAE Body System, and whether the event was a hematologic toxicity or non-hematologic toxicity. (NCT01769209)
Timeframe: 45 days
| Intervention | Treatment-related adverse events (Number) |
|---|
| Blood and Lymphatic System Disorders | Gastrointestinal Disorders | Hepatobiliary disorders | Infections and Infestations | Investigations | Metabolism and Nutrition Disorders | Nervous System Disorders | Respiratory, Thoracic and Mediastinal Disorders | Vascular Disorders | Hematologic Toxicity | Non-hematologic Toxicity |
|---|
| Bortezomib + Chemotherapy | 109 | 9 | 2 | 17 | 78 | 49 | 1 | 1 | 2 | 63 | 52 |
Overall Survival (OS) in Participants Who Experienced Complete Response or Complete Response With Incomplete Count Recovery
(NCT01829503)
Timeframe: Up to 38 months (median follow-up = 25.4 months)
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine | 15.7 |
Overall Survival (OS) in Participants Who Experienced Complete Response, Complete Response With Incomplete Count Recovery, or Partial Response
(NCT01829503)
Timeframe: Up to 38 months (median follow-up = 25.4 months)
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine | 15.7 |
Overall Survival (OS) in Participants Who Experienced Complete Response
(NCT01829503)
Timeframe: Up to 38 months (median follow-up = 25.4 months)
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine | 18.9 |
Overall Survival (OS)
(NCT01829503)
Timeframe: Up to 38 months (median follow-up = 25.4 months)
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine | 10.8 |
Relapse-Free Survival in Participants With Complete Response or Complete Response With Incomplete Count Recovery.
(NCT01829503)
Timeframe: Up to 38 months
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine | 11.7 |
Relapse-Free Survival in Participants With Complete Response, Complete Response With Incomplete Count Recovery or Partial Response, and Received Maintenance Therapy
(NCT01829503)
Timeframe: Up to 38 months
| Intervention | months (Median) |
|---|
| Decitabine + Cytarabine + Maintenance Therapy | 11.5 |
Demographic Characteristics and Clinical Measures as Potential Predictors of Overall Survival (OS)
Median number of months of survival per individual demographic characteristics and clinical measures. (NCT01829503)
Timeframe: Up to 38 months (median follow-up = 25.4 months)
| Intervention | months (Median) |
|---|
| Age ≤ 75 years | Age > 75 years | Sex - Female | Sex - Male | ECOG status 0 | ECOG status 1 | ECOG status 2 | Charlson co-morbidity status ≤ 6 | Charlson co-morbidity status > 6 | FLT and NPM1 Status: favorable | FLT and NPM1 Status: intermediate | FLT and NPM1 Status: adverse | AML Type-Primary AML | AML Type-AML with MDS changes | AML Type-Treatment-related AML | WBC ≤ 5.25 µ/L | WBC > 5.25 µ/L | Hematocrit ≤ 27.9% | Hematocrit > 27.9% | Platelets ≤ 54.5 µ/L | Platelets > 54.5 µ/L | Albumin ≤ 3.4 gm/dL | Albumin > 3.4 gm/dL | Creatinine ≤ 0.97 mg/dL | Creatinine > 0.97 mg/dL | Bilirubin ≤ 0.8 mg/dL | Bilirubin > 0.8 mg/dL | LDH ≤ 233 IU/L | LDH > 233 IU/L | Bone marrow blasts ≤ 53.65% | Bone marrow blasts > 53.65% | Peripheral blasts ≤ 13% | Peripheral blasts > 13% |
|---|
| Decitabine + Cytarabine | 12.4 | 9.7 | 11.0 | 10.6 | 16.0 | 12.6 | 4.2 | 14.3 | 7.4 | 18.9 | 7.6 | 14.3 | 10.3 | 11.5 | 12.4 | 14.9 | 7.6 | 13.0 | 10.5 | 10.4 | 15.4 | 10.8 | 13.6 | 10.6 | 14.9 | 10.4 | 13.6 | 14.4 | 6.9 | 14.9 | 7.6 | 14.0 | 7.6 |
Functional Assessment of Cancer Therapy: Health-related Quality of Life (HRQOL) Measure
"The FACT-Leu Health-related Quality of Life (HRQOL) Measure is a 27-item FACT-G scale plus a 17-item leukemia sub-scale. The FACT-G contains uses Likert scale 0-4, with 0 =not at all and 4 =very much. The total score can be 0-108 and includes 7 items related Physical Well-being (PWB), 7 items related to Social Well-being (SWB), 6 items related to Emotional Well-being (EWB) and 7 items related to Functional Well-Being (FWB). Higher scores are better. Responses based on how patients felt in the past 7 days. FACT-Leu uses a Likert scale (0 to 4, with 0= not at all and 4= very much). The total score for the 17 items can be 0-68. Higher scores are better. The FACT-Leu total is the sum of FACT-G and FACT Leu and ranges from 0-176. Higher scores are better. FACT Trial Outcome Index is derived by adding scores on the PWB and FWB sub-scales to the leukemia sub-scales. The total for this index score is from 0-124. Higher scores are better." (NCT01829503)
Timeframe: Baseline to Post-treatment, up to 5 years
| Intervention | units on a scale (Mean) |
|---|
| Baseline FACT-LEU Subscale | Baseline FACT Trial Outcome Index | Baseline FACT-LEU Total | Baseline FACT-G Total | Baseline FACT-G - Physical Well-Being | Baseline FACT-G - Social Well-Being | Baseline FACT-G - Emotional Well-Being | Baseline FACT-G - Functional Well-Being | Post-treatment LEU Subscale | Post-treatment FACT Trial Outcome Index | Post-treatment FACT-LEU Total | Post-treatment FACT-G Total | Post-treatment FACT-G - Physical Well-Being | Post-treatment FACT-G - Social Well-Being | Post-treatment FACT-G - Emotional Well-Being | Post-treatment FACT-G - Functional Well-Being |
|---|
| Decitabine + Cytarabine + Maintenance Therapy | 52.05 | 92.90 | 135.40 | 83.57 | 22.75 | 24.73 | 17.30 | 17.16 | 51.78 | 92.50 | 137.26 | 84.23 | 23.20 | 24.72 | 18.07 | 16.62 |
Number of Participants by Best Clinical Response Experienced
The number of participants who experienced either a Complete Response, Complete Response with Incomplete Count Recovery, Partial Response, or Progressive Disease. Complete response: Less than 5% blasts in an aspirate sample of a patient who has an absolute neutrophil count of >1000µ/L and platelets >100,000µ/L; Complete response with incomplete count recovery: Complete response except for residual neutropenia (<1000µ/L) or thrombocytopenia (<100,000µ/L) Partial response: Decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate; Progressive disease: Failure to achieve complete response or partial response (NCT01829503)
Timeframe: Up to 38 months
| Intervention | Participants (Number) |
|---|
| Complete Response | Complete Response with Incomplete Count Recovery | Partial Response | Progressive Disease |
|---|
| Decitabine + Cytarabine | 20 | 6 | 6 | 7 |
Numbers of Patients (Out of 44) Experiencing Adverse Events With CTCAE Grade ≥ 3 or Adverse Events Grade ≥ 4
The number of participants (out of 44) experiencing adverse events, with CTCAE Grade ≥ 3 or Adverse Events Grade ≥ 4 (NCT01829503)
Timeframe: Up to 38 months
| Intervention | Participants (Number) |
|---|
| Adverse Events Grade ≥ 3 | Adverse Events Grade ≥ 4 |
|---|
| Decitabine + Cytarabine | 44 | 41 |
Proportion of Participants With Clinical Response (CR)
The number of participants (out of 39) who experienced Clinical Response as Complete Response, or, Complete Response + Complete Response with Incomplete Count Recovery (exact Clopper-Pearson confidence interval). (NCT01829503)
Timeframe: Up to 38 months
| Intervention | Proportion of participants (Number) |
|---|
| Complete | Complete + Complete with Incomplete Count Recovery |
|---|
| Decitabine + Cytarabine | 0.51 | 0.67 |
Proportion of Participants With Survival to Four and Eight Weeks and One Year
The proportion of all participants experiencing four and eight-week mortality, or, who were alive at one year. (NCT01829503)
Timeframe: Up to one year (4 weeks, 8 weeks, and one year)
| Intervention | Proportion of participants (Number) |
|---|
| Death Within 4 Weeks | Death Within 8 Weeks | Alive at One Year |
|---|
| Decitabine + Cytarabine | 0.023 | 0.091 | 0.48 |
Complete Clinical Response
Number of patients with newly diagnosed Acute Myeloid Leukemia who achieved Complete Response to therapy as determined by bone marrow biopsy evaluation. A CR designation required that the patient achieved a morphologic leukemia-free state and an absolute neutrophil count greater than or equal to 1.0 x 10^9/l, a platelet count greater than or equal to 100 x 10^9/l, and no evidence of extramedullary disease. (NCT01960387)
Timeframe: Between 14 and 28 days from start of study treatment
| Intervention | participants (Number) |
|---|
| Clofarabine (40mg/m^2/Day) + Cytarabine (1g/m^2/Day) | 2 |
Disease-free Survival
Percentage of patients who survive without any signs or symptoms of cancer at 1 year. (NCT01969435)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 70 |
Disease-free Survival
Percentage of patients who survive without any signs or symptoms of cancer at 2 years. (NCT01969435)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 64 |
Overall Survival (OS) Rate
(NCT01969435)
Timeframe: Median follow-up 15.4 months (range 4.7-24.6)
| Intervention | percentage of participants (Number) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 10 |
Progression-free Survival (PFS) Rate
PFS - Time from start of treatment to the time of progression or death, whichever occurs first. (NCT01969435)
Timeframe: 6 months
| Intervention | percentage of participants (Median) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 84 |
Progression-free Survival Rate (PFS)
(NCT01969435)
Timeframe: 1 year
| Intervention | percentage of participants (Median) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 70 |
Relapse Free Survival
(NCT01969435)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 0 |
Time to Engraftment (Neutrophil)
Time from the date of the transplant to the date of neutrophil engraftment. (NCT01969435)
Timeframe: Assessed up to day 30
| Intervention | days (Median) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 10 |
Time to Engraftment (Platelet)
Time from the date of transplant to the date of platelet engraftment. (NCT01969435)
Timeframe: Assessed up to day 100
| Intervention | days (Median) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 19 |
Treatment-related Mortality (TRM)
TRM is defined as death not due to progressive lymphoma prior to Day 100 after transplant (NCT01969435)
Timeframe: 100 days
| Intervention | percentage of participants (Number) |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 0 |
Efficacy as Measured by Response Rates
"The response rates according to each category of response Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) will be summarized by the proportion of patients meeting each criterion.~Evaluated using PET or CT scan and Revised Response Criteria for Malignant Lymphoma" (NCT01969435)
Timeframe: Up to Day 100
| Intervention | percentage of participants (Number) |
|---|
| Complete response | Partial response | Stable disease | Progressive disease |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 84 | 4 | 0 | 12 |
Safety and Toxicity as Measured by Treatment Related Non-hematologic Adverse Events
Adverse events will be assessed using the National Cancer Institute (NCI)-CTCAE version 4.0. Number of events, grade 2 or higher, occurring in 10% or greater of participants. Grade 2 diarrhea and Grade 2 nausea/vomiting were not recorded. (NCT01969435)
Timeframe: Day -7 through Day 30
| Intervention | participants (Number) |
|---|
| Fever neutropenia | Fever | Bacteremia | Clostridium difficile | Respiratory infection | Mucosal infection | Skin infection | Genito-urinary tract infection | Hypotension | Abdominal pain | Diarrhea | Mucositis oral | Liver enzymes increased | Bilirubin increased | Dehydration | Hyperglycemia | Hypoalbuminemia | Hypocalcemia | Hypokalemia | Hypophosphatemia | Pain | Headache | Hypoxia | Rash |
|---|
| Melphalan, Carmustine, Etoposide, Cytarabine (BEAM) | 34 | 6 | 7 | 3 | 5 | 7 | 3 | 3 | 15 | 5 | 8 | 27 | 5 | 5 | 5 | 6 | 10 | 12 | 14 | 35 | 10 | 7 | 9 | 8 |
Minimal Residual Disease Negative Complete Remission Rate in Patients With Newly Diagnosed Disease (Phase II)
Remission Rate defined as Recist Category of Complete Resposne (CR) Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size(<10 mm short axis). (NCT02044796)
Timeframe: Up to day 45 after start of second course of induction chemotherapy
| Intervention | Participants (Count of Participants) |
|---|
| Newly Diagnosed Group | 95 |
| Relapsed/Refractory | 22 |
Number of Participants With Dose Limiting Toxicities of Mitoxantrone (Phase I, Dose Level 4)
Defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33%, graded according to NCI Common Terminology Criteria for Adverse Events version 4.0 (NCT02044796)
Timeframe: Up to day 45 after start of induction chemotherapy
| Intervention | Participants (Count of Participants) |
|---|
| Newly Diagnosed Group | 1 |
| Relapsed/Refractory Group | 2 |
Overall Survival (Phase II)
Number of subjects that have survived (NCT02044796)
Timeframe: From date of randomization until the date of death from any cause, assessed up to 12 months
| Intervention | Participants (Number) |
|---|
| Phase 2 Newly Diagnosed Group 18 mg/m^2 | 66 |
| Phase 2 Relapsed/Refractory Group 16 mg/m^2 | 13 |
Remission Rate (Complete Remission and Complete Remission With Incomplete Platelet Count Recovery) of This Regimen in Patients With Relapsed/Refractory Disease (Phase II)
(NCT02044796)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2 Relapsed/Refractory Group 16 mg/m^2 | 24 |
30 Day Survival Rate
Percentage of participants who were alive 30 days after starting induction treatment. (NCT01238211)
Timeframe: 30 days
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 97 |
Complete Response Rate
Percentage of participants who achieve a CR. Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x 10^9/L and platelet count > 100 x 10^9/L, and normal bone marrow differential (< 5% blasts). (NCT01238211)
Timeframe: 60 months
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 90 |
Cumulative Incidence of Death
(NCT01238211)
Timeframe: 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 15 |
Cumulative Incidence of Relapse
(NCT01238211)
Timeframe: 60 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 10 |
Disease-free Survival
Disease free survival (DFS) is defined as the time from achievement of CR to relapse or death, whichever comes first. The 3 year DFS rate with 95% CI was estimated using the Kaplan-Meier method. (NCT01238211)
Timeframe: 3 years
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 75 |
Event-free Survival
"Event free survival (EFS) is defined as the time from registration to failure to achieve complete remission (CR), relapse after CR is attained or death, whichever comes first. The 1 year EFS rate with 95% CI was estimated using the Kaplan-Meier method,~Complete remission (CR) is defined as: disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count > 1.0 x 10^9/L and platelet count > 100 x 10^9/L, and normal bone marrow differential (< 5% blasts)." (NCT01238211)
Timeframe: 1 year
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 83 |
Overall Survival
Overall survival (OS) is defined as time from registration to death. The 3 year OS rate with 95% CI was estimated using the Kaplan-Meier method. (NCT01238211)
Timeframe: 3 years
| Intervention | percentage of patients (Number) |
|---|
| Treatment (Daunorubicin Hydrochloride, Cytarabine, Dasatinib) | 77 |
Complete Remission (CR)
Complete disappearance of all clinical evidence of disease (NCT03504410)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| CPI-613 + HD Cytarabine and Mitoxantrone | 20 |
| Control (HAM) and Control Sub-groups (MEC and FLAG) | 22 |
Overall Survival
Overall survival will be estimated. (NCT02483000)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (PRIT) | 2 |
Dosimetry of Yttrium Y 90 DOTA-biotin
Assessed using OLINDA dosimetry software. The estimated dose to normal organs and tumor sites will be described based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 DOTA-biotin. (NCT02483000)
Timeframe: Up to 7 days after infusion
| Intervention | cGy/mCi (Median) |
|---|
| Liver | Spleen | Lungs | Kidneys | Bone Marrow | Brain |
|---|
| Treatment (PRIT) | 2.5 | 3.73 | 0.229 | 11.4 | 3.75 | 0.229 |
Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Descriptive statistics on the number and percent toxicities will be calculated. (NCT02483000)
Timeframe: Up to 30 days after transplant
| Intervention | Participants (Count of Participants) |
|---|
| Serious Adverse Events | Other (Not Including Serious) Adverse Events |
|---|
| Treatment (PRIT) | 2 | 2 |
2-year Overall Survival Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL.
(NCT02535806)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment Arm | 1 |
Number of Subject With Adverse Events
Toxicities were assessed and graded according to CTCAE v 4.0. (NCT02535806)
Timeframe: 36 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment Arm | 1 |
Post-induction Level of Minimal Residual Disease Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL.
Percent of Cells Positive for Minimal residual disease measured by multiparameter flow cytometry (NCT02535806)
Timeframe: 36 days
| Intervention | Percentage of Cells Positive for MRD (Mean) |
|---|
| Treatment Arm | 0.65 |
Remission Rate Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL.
Number of patients with bone marrow blast percentage <5% after treatment (NCT02535806)
Timeframe: 36 days
| Intervention | Participants (Count of Participants) |
|---|
| Treatment Arm | 2 |
Event-Free Survival (EFS)
EFS defined as time from the treatment start till treatment failure, relapse, or death whichever comes first. Event Free Survival will be presented by median EFS, which is the time point at which the cumulative survival drops below 50%. If there is no median survival (not reached), it means the cumulative survival was more than 50%. (NCT02464657)
Timeframe: 56 days
| Intervention | Months (Median) |
|---|
| Ph 2 Nivolumab (3mg) + Idarubicin + Cytarabine | NA |
Maximum Tolerated Dose (MTD) of Nivolumab
MTD is highest dose level in which <2 patients of 6 develop first cycle dose-limiting toxicity (DLT). (NCT02464657)
Timeframe: 28 days
| Intervention | mg/kg (Number) |
|---|
| Ph 1 - Nivolumab (1mg) + Idarubicin + Cytarabine | NA |
| Ph 1 - Nivolumab (3mg) + Idarubicin + Cytarabine | 3 |
Overall Survival
Overall survival was defined as the time from the start of treatment to death or date of last follow-up. (NCT02464657)
Timeframe: Up to 2 years and 10 Months
| Intervention | Months (Median) |
|---|
| Ph 2 Nivolumab (3mg) + Idarubicin + Cytarabine | 18.54 |
Relapse Free Survival
Relapse-free survival was defined as the time from treatment response to date of relapse or death, whichever occurred first. (NCT02464657)
Timeframe: Up to 2 years and10 Months
| Intervention | Months (Median) |
|---|
| Ph 2 - Nivolumab (3mg) + Idarubicin + Cytarabine | 18.54 |
Disease-Free Survival at 2-Year Post-Transplant by Cytogenetic Risk
Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. (NCT00534469)
Timeframe: Kaplan-Meier estimate 2 years post treatment
| Intervention | Proportion of pts alive in remission (Number) |
|---|
| Unfavorable Risk Cytogenetics | 0.33 |
| Intermediate Risk Cytogenetics | 0.75 |
| Favorable Risk Cytogenetics | 0.75 |
| Unknown Risk: Rejected Cytogenetics Study | 0.73 |
Disease-Free Survival at 2-Year Post-Transplant
Kaplan-Meier estimates at 2-years post-transplant, with 95% confidence intervals based on logit limit transformation of Greenwood's variance. Outcome is death or relapse, censor is alive in continual complete remission at the date of last clinical disease assessment. (NCT00534469)
Timeframe: Estimate at 2 years post treatment
| Intervention | Proportion of pts alive in remission (Number) |
|---|
| HD ARA-C Intermediate Cytogenetics | 0.65 |
Number of Relevant Toxicities Related to Therapy
"Events were graded using CTCAE v. 4.0. All toxicities will be monitored until the completion of therapy (up to 500 days) for patients that do not go on to bone marrow transplant. If a patient goes on to receive a bone marrow transplant, at that point, they will no longer be monitored for toxicity, as any further toxicities may be secondary to the transplant and not the study regimen.~This outcome reports those toxicities that are that were possibly, probably or definitely related to therapy. Participants were separately monitored for frequency of grade 5 events, grade 4 sepsis, grade 4 hemorrhage, and grade 4 hepatic toxicity across all patients in the stratum. Grade 4 and 5 events that are clearly and incontrovertibly due to extraneous causes or disease progression will be excluded. Higher grade events are considered more severe than lower grade." (NCT02419755)
Timeframe: From on-therapy date up to 18 months
| Intervention | events (Number) |
|---|
| Grade 5: death | Grade 4: sepsis | Grade 4: hemorrhage | Grade 4: hepatic toxicity |
|---|
| Stratum 1: Myeloid Malignancies | 1 | 0 | 0 | 0 |
,| Stratum 2: ALL and MLM | 3 | 2 | 1 | 0 |
Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
Karyotyping was required locally, at screening and at least once during the study in participants who had abnormal cytogenetics at baseline and who achieved CR/CRi. Data presented below are for participants who achieved CR/CRi per EAC and had abnormal karyotype at screening. (NCT01564784)
Timeframe: Up to approximately 4 weeks (EoT) from last dose of study drug
| Intervention | Percentage of Participants (Number) |
|---|
| Inotuzumab Ozogamicin | 3.7 |
| Defined Investigator's Choice of Chemotherapy | 18.2 |
Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
DoR was defined as time from date of first response in responders (CR/CRi per Investigator assessment) to date of PFS event (i.e. death, progressive disease [objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status] or starting new induction therapy or post-therapy stem cell transplant [SCT] without achieving CR/CRi). Responders without PFS events were censored at the last valid disease assessment including follow-up. (NCT01564784)
Timeframe: Up to 2 years from randomization
| Intervention | Months (Median) |
|---|
| Inotuzumab Ozogamicin | 5.4 |
| Defined Investigator's Choice of Chemotherapy | 3.5 |
Overall Survival (OS)
OS was defined as the time from randomization to date of death due to any cause. Participants last known to be alive were censored at date of last contact. (NCT01564784)
Timeframe: Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.
| Intervention | Months (Median) |
|---|
| Inotuzumab Ozogamicin | 7.7 |
| Defined Investigator's Choice of Chemotherapy | 6.2 |
Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
MRD analysis was performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study, were sent to the central laboratory and analyzed using multiparametric flow cytometry. The antibody combinations were designed to maximize discrimination between normal and abnormal cells of B-cell lineage and similar maturational stage and included antibodies detecting cluster of differentiation (CD) 9, CD10, CD13, CD19, CD20, CD33, CD34, CD38, CD45, CD58, CD66c, and CD123. A peripheral blood sample was provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity was considered to have been achieved if the lowest value of MRD from the first date of CR/CRi to EoT was <1 × 10^-4 blasts/nucleated cells. (NCT01564784)
Timeframe: Up to approximately 4 weeks (EoT) from last dose of study drug
| Intervention | Percentage of Participants (Number) |
|---|
| Inotuzumab Ozogamicin | 78.4 |
| Defined Investigator's Choice of Chemotherapy | 28.1 |
Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy. (NCT01564784)
Timeframe: Up to 19 weeks from last dose
| Intervention | Percentage of Participants (Number) |
|---|
| Inotuzumab Ozogamicin | 42.7 |
| Defined Investigator's Choice of Chemotherapy | 11.1 |
Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
CR was the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi was defined as CR except ANC <1000/μL &/or platelets <100,000/μL. (NCT01564784)
Timeframe: Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose
| Intervention | Percentage of Participants (Number) |
|---|
| Inotuzumab Ozogamicin | 80.7 |
| Defined Investigator's Choice of Chemotherapy | 29.4 |
Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
VOD/SOS was defined as the occurrence of 2 out of the following 3 clinical criteria: 1) total serum bilirubin level >34 micromoles per liter (μmol/L) (>2.0 milligrams per deciliter [mg/dL]), 2) an increase in liver size from baseline or development of right upper quadrant pain of liver origin and 3) sudden weight gain >2.5% (eg, within a 72 hour period) because of fluid accumulation in the weeks following infusion of study drug or chemotherapy, or HSCT conditioning/preparative therapy, or development of ascites not present at baseline following such exposures AND the absence of other explanations for these signs and symptoms, OR development of bilirubin elevation, weight gain, or hepatomegaly plus histologic abnormalities on liver biopsy demonstrating hepatocyte necrosis in zone 3 of the liver acinus, sinusoidal fibrosis, and centrilobular hemorrhage, with or without fibrosis of the terminal hepatic venules. (NCT01564784)
Timeframe: Up to 2 years from randomization
| Intervention | Percentage of Participants (Number) |
|---|
| Inotuzumab Ozogamicin | 22.8 |
| Defined Investigator's Choice of Chemotherapy | 8.6 |
Progression-Free Survival (PFS)
PFS was defined as time from date of randomization to earliest date of the following events: death, progressive disease (objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status) and starting new induction therapy or post-therapy SCT without achieving CR/CRi. Participants without a PFS event at time of analysis were censored at the last valid disease assessment. In addition, participants with documentation of an event after an unacceptably long interval (>28 weeks if there was post-baseline disease assessment, or >12 weeks if there was no post-baseline assessment) since the previous disease assessment were censored at the time of the previous assessment (date of randomization if no post-baseline assessment). Post-study treatment follow-up disease assessments was included. Kaplan-Meier method used and 2-sided 95% confidence interval (CI) calculated based on the Brookmeyer and Crowley method. (NCT01564784)
Timeframe: Up to 2 years from randomization
| Intervention | Months (Median) |
|---|
| Inotuzumab Ozogamicin | 5.0 |
| Defined Investigator's Choice of Chemotherapy | 1.7 |
Change From Baseline in EQ-5D VAS
"The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting no problems, some problems, and extreme problems. The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state." (NCT01564784)
Timeframe: Day 1 of each cycle prior to dosing and EoT
| Intervention | Score on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | EoT |
|---|
| Defined Investigator's Choice of Chemotherapy | 5.90 | 19.67 | 44.00 | NA | NA | -0.52 |
,| Inotuzumab Ozogamicin | 5.81 | 8.13 | 7.13 | 7.62 | 15.09 | 4.62 |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
This questionnaire comprised 30 questions within which are 9 multi-item scales & 6 single-item measures. There are 5 functional scales; physical, role, cognitive, emotional & social, 3 symptom scales; fatigue, pain, & nausea & vomiting, & a global health status/quality of life (QoL) scale. There are 5 single item measures assessing additional symptoms commonly reported by cancer patients (loss of appetite, insomnia, constipation, diarrhea, & dyspnea) & a single item concerning perceived financial impact of the disease. Most questions used a 4 point scale (1='not at all' to 4='very much'); 2 questions used a 7-point scale (1='very poor' to 7='excellent'). Scores were averaged & transformed to a scale ranging from 0 to 100; a higher score indicates a better level of functioning or greater degree of symptoms. (NCT01564784)
Timeframe: Day 1 of each cycle prior to dosing and EoT
| Intervention | Score on a scale (Mean) |
|---|
| Physical Functioning C2D1 | Physical Functioning C3D1 | Physical Functioning C4D1 | Physical Functioning C5D1 | Physical Functioning C6D1 | Physical Functioning EoT | Role Functioning C2D1 | Role Functioning C3D1 | Role Functioning C4D1 | Role Functioning C5D1 | Role Functioning C6D1 | Role Functioning EoT | Emotional Functioning C2D1 | Emotional Functioning C3D1 | Emotional Functioning C4D1 | Emotional Functioning C5D1 | Emotional Functioning C6D1 | Emotional Functioning EoT | Cognitive Functioning C2D1 | Cognitive Functioning C3D1 | Cognitive Functioning C4D1 | Cognitive Functioning C5D1 | Cognitive Functioning C6D1 | Cognitive Functioning EoT | Social Functioning C2D1 | Social Functioning C3D1 | Social Functioning C4D1 | Social Functioning C5D1 | Social Functioning C6D1 | Social Functioning EoT | Global Health Status C2D1 | Global Health Status C3D1 | Global Health Status C4D1 | Global Health Status C5D1 | Global Health Status C6D1 | Global Health Status EoT | Dyspnoea C2D1 | Dyspnoea C3D1 | Dyspnoea C4D1 | Dyspnoea C5D1 | Dyspnoea C6D1 | Dyspnoea EoT | Insomnia C2D1 | Insomnia C3D1 | Insomnia C4D1 | Insomnia C5D1 | Insomnia C6D1 | Insomnia EoT | Appetite Loss C2D1 | Appetite Loss C3D1 | Appetite Loss C4D1 | Appetite Loss C5D1 | Appetite Loss C6D1 | Appetite Loss EoT | Constipation C2D1 | Constipation C3D1 | Constipation C4D1 | Constipation C5D1 | Constipation C6D1 | Constipation EoT | Diarrhoea C2D1 | Diarrhoea C3D1 | Diarrhoea C4D1 | Diarrhoea C5D1 | Diarrhoea C6D1 | Diarrhoea EoT | Financial Difficulties C2D1 | Financial Difficulties C3D1 | Financial Difficulties C4D1 | Financial Difficulties C5D1 | Financial Difficulties C6D1 | Financial Difficulties EoT | Fatigue C2D1 | Fatigue C3D1 | Fatigue C4D1 | Fatigue C5D1 | Fatigue C6D1 | Fatigue Eot | Nausea and Vomiting C2D1 | Nausea and Vomiting C3D1 | Nausea and Vomiting C4D1 | Nausea and Vomiting C5D1 | Nausea and Vomiting C6D1 | Nausea and Vomiting EoT | Pain C2D1 | Pain C3D1 | Pain C4D1 | Pain C5D1 | Pain C6D1 | Pain EoT |
|---|
| Defined Investigator's Choice of Chemotherapy | 0.32 | -13.33 | 0.00 | NA | NA | -8.17 | -1.59 | -11.11 | 0.00 | NA | NA | -12.37 | 4.76 | -19.44 | 0.00 | NA | NA | 4.35 | 0.00 | -5.56 | 16.67 | NA | NA | 0.54 | -2.38 | -27.78 | 0.00 | NA | NA | -2.15 | 0.40 | -16.67 | 8.33 | NA | NA | -0.40 | -7.94 | 11.11 | 0.00 | NA | NA | 0.54 | 1.59 | 0.00 | 0.00 | NA | NA | 0.00 | 3.17 | 0.00 | 0.00 | NA | NA | 11.83 | 0.00 | 0.00 | 0.00 | NA | NA | -0.54 | -1.59 | -11.11 | 0.00 | NA | NA | 3.76 | 0.00 | 0.00 | 0.00 | NA | NA | 2.19 | 5.82 | 22.22 | -11.11 | NA | NA | 5.73 | -0.79 | 0.00 | -16.67 | NA | NA | 3.49 | -7.14 | -5.56 | -33.33 | NA | NA | -7.26 |
,| Inotuzumab Ozogamicin | 0.48 | 3.15 | 5.33 | 11.52 | 7.22 | -3.38 | 5.45 | 11.81 | 16.67 | 12.88 | 16.67 | 1.32 | 5.21 | 7.41 | 5.69 | 6.82 | 2.78 | -0.91 | 4.05 | 5.79 | 4.58 | 0.76 | -8.33 | 0.83 | 4.20 | 5.56 | 10.42 | 12.88 | 16.67 | 1.82 | 3.98 | 9.38 | 11.25 | 8.71 | 0.69 | 0.00 | -5.41 | -7.41 | -12.50 | -3.03 | -2.78 | -2.31 | -2.40 | -9.26 | -7.50 | -4.55 | -11.11 | -2.31 | -4.20 | -8.33 | -11.67 | -6.06 | 2.78 | -1.32 | -1.21 | 0.47 | -2.50 | 0.00 | 5.56 | 2.64 | -3.30 | -5.09 | -0.83 | -9.52 | -2.78 | 2.31 | -1.80 | 0.47 | -1.67 | -3.03 | -5.56 | 0.33 | -4.10 | -8.33 | -9.17 | -7.32 | 0.00 | -0.33 | 0.15 | -4.63 | -3.33 | 2.27 | 0.00 | -0.17 | -8.86 | -8.56 | -4.17 | 0.76 | -2.78 | -1.98 |
Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
"The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting no problems, some problems, and extreme problems. The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health)." (NCT01564784)
Timeframe: Day 1 of each cycle prior to dosing and EoT
| Intervention | Score on a scale (Mean) |
|---|
| Cycle 2, Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | EoT |
|---|
| Defined Investigator's Choice of Chemotherapy | 0.02 | -0.08 | 0.00 | NA | NA | -0.04 |
,| Inotuzumab Ozogamicin | 0.00 | 0.01 | 0.04 | 0.04 | 0.03 | -0.01 |
Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
Blood samples were collected and analyzed for inotuzumab ozogamicin serum concentrations using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) method with a lower limit of quantification of 1.0 nanograms per milliliter (ng/mL). Cmax was the maximum observed concentration occurring between 0-8 hours post-dose. Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours. n = number of observations (non-missing concentrations). (NCT01564784)
Timeframe: Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4
| Intervention | ng/mL (Mean) |
|---|
| Cmax (Cycle 1 Day 1, 1 hour post-dose) (n=128) | Ctrough (Cycle 4 Day 1, pre-dose) (n=46) | Cmax (Cycle 4 Day 1, 1 hour post-dose) (n=37) |
|---|
| Inotuzumab Ozogamicin | 211 | 57.9 | 308 |
Number of Participants With Objective Response
Objective response: Complete Response/Remission (CR) defined as a bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10^9/Liters or more and platelet count of 100*10^9/Liters or more; Complete Response with Platelets/remission without platelet recovery (CRp) defined as a complete response except for a platelet less than 100*10^9/Liters and transfusion independent; and Partial Response/Remission defined as peripheral blood count recovery as for CR with decrease in marrow blasts >/= 50% and not more than 6-25% abnormal cells in the marrow. (NCT00480987)
Timeframe: After 2 months
| Intervention | Participants (Number) |
|---|
| Complete response | Complete response with platelets | Partial response |
|---|
| Oxaliplatin + Cytarabine + Fludarabine | 3 | 2 | 0 |
Number of Participants Adherent to Readmission Recommendations
This measure will record the number of subjects who complete as 100% compliance with medical provider recommendations to be admitted to the hospital (except for reasons of adopting a palliative or hospice approach to care). Subjects not achieving a 100% rate of compliance will be considered non-adherent to the recommendations. (NCT03988205)
Timeframe: Day 60
| Intervention | Participants (Count of Participants) |
|---|
| Intervention | 3 |
Number of Participants Adherent to Recommendations
This measure will record the number subjects who adhere to outpatient follow-up appointments and readmission recommendations. Subjects completing 95% of their recommended outpatient visits will be considered to be adherent to the recommendations. (NCT03988205)
Timeframe: Day 60
| Intervention | Participants (Count of Participants) |
|---|
| Intervention | 3 |
Probability of Event-free Survival (EFS)
"For EFS, relapse and second malignancies are considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. Kaplan-Meier estimates of the OS and EFS curves are computed, along with estimates of standard errors by Peto's method.~Please note the unit of measurement of probabilities are percentages." (NCT01451515)
Timeframe: Two years post therapy.
| Intervention | percentage of event-free patients (Number) |
|---|
| Stratum 1 | 91.7 |
| Stratum 2 | 71.4 |
| Stratum 3 | 100 |
| All Enrollments | 86.96 |
Probability of Overall Survival (OS)
"For OS, only deaths are considered failures for OS. Kaplan-Meier estimates of the OS curves are computed along with estimates of standard errors by Peto's method.~Please note the unit of measurement of probabilities are percentages." (NCT01451515)
Timeframe: Two years post therapy.
| Intervention | percentage of patients alive (Number) |
|---|
| Stratum 1 | 91.7 |
| Stratum 2 | 71.4 |
| Stratum 3 | 100 |
| All Enrollments | 86.96 |
Minimal Disseminated Disease (MDD)
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable) (NCT01451515)
Timeframe: At Diagnosis
| Intervention | participants (Number) |
|---|
| Negative | Positive |
|---|
| Stratum 1 | 4 | 1 |
,| Stratum 2 | 2 | 3 |
,| Stratum 3 | 0 | 4 |
Minimal Residual Disease (MRD)
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable) (NCT01451515)
Timeframe: Day 8
| Intervention | participants (Number) |
|---|
| Negative | Positive |
|---|
| Stratum 1 | 8 | 0 |
,| Stratum 2 | 4 | 1 |
,| Stratum 3 | 0 | 4 |
Area Under the Ulocuplumab Concentration-time Curve From Time Zero to the Last Quantifiable Concentration [AUC(0-T)] - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~AUC(0-T) calculated by log- and linear-trapezoidal summation~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Cycle 1 Day 1
| Intervention | µg.h/mL (Geometric Mean) |
|---|
| ULO 600mg + LDAC - Ph1 | 9455.529 |
| ULO 800mg + LDAC - Ph1 | 21158.725 |
| ULO 800mg + LDAC - Ph2 | 8152.698 |
| ULO 1000mg + LDAC - Ph2 | 13744.382 |
| LDAC - Ph2 | 16502.463 |
Area Under the Ulocuplumab Concentration-time Curve in One Dosing Interval [AUC(TAU)] - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Cycle 1 Day 1
| Intervention | µg.h/mL (Geometric Mean) |
|---|
| ULO 600mg + LDAC - Ph1 | 9455.529 |
| ULO 800mg + LDAC - Ph1 | 21158.725 |
| ULO 800mg + LDAC - Ph2 | 10082.624 |
| ULO 1000mg + LDAC - Ph2 | 13826.833 |
| LDAC - Ph2 | 14257.807 |
Best Overall Response (BOR) - Phase 1
Investigator assessed best overall response prior to the initiation of any alternative therapy for Phase 1 participants. (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 1 |
| ULO 800mg + LDAC - Ph1 | 3 |
Best Overall Response (BOR) - Phase 2
"The phase 2 primary endpoint was based on the rate of Complete Remission (CR/CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 primary analysis was conducted after all participants had an opportunity for 6 months of follow-up.~Complete remission rate: CR + CRi, confidence interval based on the Clopper and Pearson method.~CR = complete response CRi = complete response, incomplete blood count" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Percentage of participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 15.4 |
| ULO 1000mg + LDAC - Ph2 | 7.1 |
| LDAC - Ph2 | 25.0 |
Duration of Response in Participants With CR/CRi Treated With LDAC Only - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Months (Median) |
|---|
| LDAC - Ph2 | 5.7 |
Duration of Response in Participants With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
This phase 2 secondary endpoint was based on the duration of complete remission prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up. (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Months (Median) |
|---|
| ULO 800mg + LDAC - Ph2 | 2.4 |
| ULO 1000mg + LDAC - Ph2 | 4.3 |
Maximum Observed Serum Concentration (Cmax) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Cycle 1 Day 1
| Intervention | µg/mL (Geometric Mean) |
|---|
| ULO 600mg + LDAC - Ph1 | 219.354 |
| ULO 800mg + LDAC - Ph1 | 265.294 |
| ULO 800mg + LDAC - Ph2 | 183.456 |
| ULO 1000mg + LDAC - Ph2 | 256.906 |
| LDAC - Ph2 | 212.564 |
Number of Deaths - Phase 1
The number of participants who died. (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 0 |
| ULO 800mg + LDAC - Ph1 | 0 |
Number of Deaths- Phase 2
"The number of participants who died.~Safety data are evaluated for deaths, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 19 |
| ULO 1000mg + LDAC - Ph2 | 10 |
| LDAC - Ph2 | 16 |
Number of Participants With >= Grade 3 AEs - Phase 1
"The number of participants with an on-study adverse event >= Grade level 3.~Safety data are evaluated for >= Grade 3 AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 3 |
| ULO 800mg + LDAC - Ph1 | 3 |
Number of Participants With Adverse Events (AEs) - Phase 1
"The number of participants with an on-study adverse event (AE).~Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 3 |
| ULO 800mg + LDAC - Ph1 | 3 |
Number of Participants With AEs - Phase 2
"The number of participants with an on-study adverse event (AE).~Safety data are evaluated for AEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 25 |
| ULO 1000mg + LDAC - Ph2 | 14 |
| LDAC - Ph2 | 22 |
Number of Participants With AEs Leading to Discontinuation - Phase 1
"The number of participants with an on-study adverse event (AE) leading to discontinuation.~Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 0 |
| ULO 800mg + LDAC - Ph1 | 0 |
Number of Participants With AEs Leading to Discontinuation - Phase 2
"The number of participants with an on-study adverse event (AE) leading to discontinuation.~Safety data are evaluated for AEs leading to discontinuation, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 7 |
| ULO 1000mg + LDAC - Ph2 | 3 |
| LDAC - Ph2 | 4 |
Number of Participants With Anti-drug Antibodies (ADA) Positive for Ulocuplumab - Phases 1 and 2
Serum samples from ulocuplumab treated participants were evaluated for the presence of anti-ulocuplumab antibodies (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 0 |
| ULO 800mg + LDAC - Ph1 | 0 |
| ULO 800mg + LDAC - Ph2 | 6 |
| ULO 1000mg + LDAC - Ph2 | 0 |
Number of Participants With Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1 - Phase 1
Safety data evaluated for DLTs. DLTs and all other toxicities were defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03). DLTs were defined based upon events that were considered to be related to ulocuplumab in combination with LDAC and that occurred during the first cycle of drug administration (28 days). (NCT02305563)
Timeframe: From first dose to end of cycle 1 (28 days)
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 0 |
| ULO 800mg + LDAC - Ph1 | 0 |
Number of Participants With SAEs - Phase 2
"The number of participants with an on-study serious adverse event (SAE).~Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 21 |
| ULO 1000mg + LDAC - Ph2 | 8 |
| LDAC - Ph2 | 15 |
Number of Participants With Serious Adverse Events (SAEs) - Phase 1
"The number of participants with an on-study serious adverse event (SAE).~Safety data are evaluated for SAEs, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ULO 600mg + LDAC - Ph1 | 2 |
| ULO 800mg + LDAC - Ph1 | 1 |
Overall Rate of Remission in Participants Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC - Phase 2
"This phase 2 secondary endpoint was based on the rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.~Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method.~CR = complete response CRi = complete response, incomplete blood count PR = partial remission" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Percentage of participants (Number) |
|---|
| ULO 800mg + LDAC - Ph2 | 19.2 |
| ULO 1000mg + LDAC - Ph2 | 7.1 |
Overall Survival (OS) - Phases 1 and 2
OS is defined as the time between the first date of treatment and the date of death due to any cause. A participant who has not died was be censored at the last known alive date. (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Months (Median) |
|---|
| ULO 800mg + LDAC - Ph2 | 3.3 |
| ULO 1000mg + LDAC - Ph2 | 3.0 |
| LDAC - Ph2 | 6.9 |
Time of Maximum Observed Ulocuplumab Serum Concentration (Tmax) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment" (NCT02305563)
Timeframe: Cycle 1 Day 1
| Intervention | hour (H) (Median) |
|---|
| ULO 600mg + LDAC - Ph1 | 1.850 |
| ULO 800mg + LDAC - Ph1 | 1.933 |
| ULO 800mg + LDAC - Ph2 | 1.500 |
| ULO 1000mg + LDAC - Ph2 | 2.117 |
| LDAC - Ph2 | 2.03 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
"Change from baseline of ECG endpoints~Heart rate measured in beats per minute (bpm)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline bpm (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 8, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 |
|---|
| ULO 600mg + LDAC - Ph1 | 26.0 | -2.3 | -1.0 | -6.0 | -6.0 | -1.0 | -3.0 | -12.0 | -9.0 | -10.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
"Change from baseline of ECG endpoints~Heart rate measured in beats per minute (bpm)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline bpm (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 14, Day 1 |
|---|
| ULO 800mg + LDAC - Ph2 | 1.8 | 5.8 | -0.1 | 4.3 | 6.8 | -3.5 | 0.7 | 7.0 | 9.3 | 5.0 | 8.0 | 14.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
"Change from baseline of ECG endpoints~Heart rate measured in beats per minute (bpm)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline bpm (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 | Cycle 16, Day 1 |
|---|
| LDAC - Ph2 | -3.0 | 1.7 | 1.3 | 8.8 | 7.4 | 6.5 | 0.8 | 0.6 | 2.0 | -0.3 | 7.0 | 4.0 | 8.0 | 18.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
"Change from baseline of ECG endpoints~Heart rate measured in beats per minute (bpm)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline bpm (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 |
|---|
| ULO 800mg + LDAC - Ph1 | 4.0 | 0.0 | -16.0 | 1.5 | -6.0 | -11.7 | -17.0 | -16.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: Heart Rate - Phases 1 and 2
"Change from baseline of ECG endpoints~Heart rate measured in beats per minute (bpm)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline bpm (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 |
|---|
| ULO 1000mg + LDAC - Ph2 | -0.9 | 12.7 | 11.0 | 10.5 | 12.0 | 11.0 | 3.0 | 10.0 | 19.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~PR interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 8, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 |
|---|
| ULO 600mg + LDAC - Ph1 | 4.0 | 8.0 | 14.0 | -2.0 | -44.0 | 4.0 | -4.0 | 4.0 | -2.0 | 0.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~PR interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 14, Day 1 |
|---|
| ULO 800mg + LDAC - Ph2 | 1.1 | -5.3 | -16.3 | -7.6 | -12.8 | -6.8 | -5.3 | -17.0 | -11.3 | -60.0 | -44.0 | -54.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~PR interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 | Cycle 16, Day 1 |
|---|
| LDAC - Ph2 | 1.2 | -1.9 | -11.9 | -24.6 | -3.4 | -8.3 | -9.4 | 0.6 | 1.0 | -1.7 | -5.0 | 3.0 | -10.0 | -2.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~PR interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 |
|---|
| ULO 800mg + LDAC - Ph1 | -14.0 | -12.0 | -13.0 | -16.0 | -19.3 | -17.3 | -10.0 | -2.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: PR Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~PR interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 |
|---|
| ULO 1000mg + LDAC - Ph2 | -5.1 | -2.8 | -10.0 | -11.0 | -2.0 | -6.0 | 6.0 | 4.0 | -4.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QRS interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 8, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 |
|---|
| ULO 600mg + LDAC - Ph1 | 0.0 | 3.3 | 0.0 | 8.0 | 6.0 | 2.0 | 2.0 | 6.0 | 2.0 | 6.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QRS interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 14, Day 1 |
|---|
| ULO 800mg + LDAC - Ph2 | 5.1 | -1.3 | 2.7 | 1.8 | -1.8 | -3.3 | 0.7 | -2.0 | -2.3 | -6.0 | -12.0 | -10.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QRS interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 | Cycle 16, Day 1 |
|---|
| LDAC - Ph2 | 4.8 | 1.4 | 6.4 | -1.4 | 5.4 | -1.5 | 2.6 | 0.0 | 9.5 | 9.0 | 10.0 | 3.5 | 8.0 | 7.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QRS interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 |
|---|
| ULO 800mg + LDAC - Ph1 | -2.0 | -2.0 | 1.0 | -4.0 | -2.7 | -2.7 | -1.0 | -4.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QRS Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QRS interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 |
|---|
| ULO 1000mg + LDAC - Ph2 | 0.5 | 2.0 | -3.3 | 2.0 | -10.0 | -8.0 | -6.0 | -4.0 | -8.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QT interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 8, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 |
|---|
| ULO 600mg + LDAC - Ph1 | -41.0 | 10.0 | -60.0 | 12.0 | 2.0 | 2.0 | 6.0 | 16.0 | 20.0 | 36.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QT interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 14, Day 1 |
|---|
| ULO 800mg + LDAC - Ph2 | 4.5 | -15.4 | 10.1 | 2.2 | -11.8 | 11.8 | 2.0 | -23.0 | -18.3 | -4.0 | -40.0 | -44.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QT interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 | Cycle 13, Day 1 | Cycle 15, Day 1 | Cycle 16, Day 1 |
|---|
| LDAC - Ph2 | 14.2 | 13.7 | -1.4 | -27.6 | -3.6 | -8.8 | 0.8 | -24.4 | -6.0 | 7.0 | -6.5 | -15.0 | -19.0 | -105.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QT interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 6, Day 1 | Cycle 7, Day 1 | Cycle 9, Day 1 | Cycle 10, Day 1 |
|---|
| ULO 800mg + LDAC - Ph1 | -5.0 | 7.0 | 35.0 | 13.0 | 6.0 | 29.3 | 37.0 | 14.0 |
Change From Baseline of Electrocardiogram (ECG) Endpoints: QT Interval - Phases 1 and 2
"Change from baseline of ECG endpoints~QT interval measured in milliseconds (msec)" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | change from baseline msec (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 3, Day 1 | Cycle 4, Day 1 | Cycle 5, Day 1 | Cycle 7, Day 1 | Cycle 8, Day 1 | Cycle 9, Day 1 | Cycle 11, Day 1 | Cycle 12, Day 1 |
|---|
| ULO 1000mg + LDAC - Ph2 | 10.4 | -10.7 | -12.7 | -5.0 | -8.0 | -24.0 | -14.0 | -22.0 | -36.0 |
Number of Participants With Laboratory Abnormalities - Phase 1
"The number of participants with an on-study laboratory abnormality.~Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03).~grades 1, 2, 3, 4, 5, unknown, with 5 being the worst outcome" (NCT02305563)
Timeframe: From first dose to 30 days post last dose
| Intervention | Participants (Number) |
|---|
| ABSOLUTE NEUTROPHIL COUNT - grade 3 | ABSOLUTE NEUTROPHIL COUNT - grade 4 | ALANINE AMINOTRANSFERASE - grade 0 | ALANINE AMINOTRANSFERASE - grade 1 | ALBUMIN - grade 0 | ALBUMIN - grade 1 | ALBUMIN - grade 2 | ALKALINE PHOSPHATASE - grade 0 | ALKALINE PHOSPHATASE grade 1 | ASPARTATE AMINOTRANSFERASE - grade 0 | ASPARTATE AMINOTRANSFERASE - grade 1 | BILIRUBIN, TOTAL - grade 0 | BILIRUBIN, TOTAL - grade 2 | CALCIUM, TOTAL - grade 0 | CALCIUM, TOTAL - grade 1 | CALCIUM, TOTAL - grade 2 | CREATINE KINASE - grade 0 | CREATININE - grade 0 | CREATININE - grade 1 | FIBRINOGEN - grade 0 | GLUCOSE, FASTING SERUM - grade 0 | GLUCOSE, FASTING SERUM - grade 1 | GLUCOSE, FASTING SERUM - grade 2 | HEMOGLOBIN - grade 2 | HEMOGLOBIN - grade 3 | LEUKOCYTES - grade 0 | LEUKOCYTES - grade 3 | LEUKOCYTES - grade 4 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 0 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 1 | LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 3 | LYMPHOCYTES (ABSOLUTE) - grade 0 | LYMPHOCYTES (ABSOLUTE) - grade 1 | LYMPHOCYTES (ABSOLUTE) - grade 2 | LYMPHOCYTES (ABSOLUTE) - grade 3 | NEUTROPHILS (ABSOLUTE) - grade 3 | NEUTROPHILS (ABSOLUTE) - grade 4 | PHOSPHORUS, INORGANIC - grade 0 | PHOSPHORUS, INORGANIC - grade 3 | PLATELET COUNT - grade 3 | PLATELET COUNT - grade 4 | POTASSIUM, SERUM - grade 0 | POTASSIUM, SERUM - grade 1 | POTASSIUM, SERUM - grade 3 | SODIUM, SERUM - grade 0 | SODIUM, SERUM - grade 1 | SODIUM, SERUM - grade 3 | URIC ACID - grade 0 | URIC ACID - grade 1 |
|---|
| ULO 600mg + LDAC - Ph1 | 0 | 3 | 2 | 1 | 1 | 0 | 2 | 2 | 1 | 3 | 0 | 3 | 0 | 1 | 0 | 2 | 3 | 2 | 1 | 1 | 1 | 2 | 0 | 1 | 2 | 0 | 1 | 2 | 2 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 3 | 3 | 0 | 0 | 3 | 1 | 0 | 2 | 2 | 0 | 1 | 3 | 0 |
,| ULO 800mg + LDAC - Ph1 | 1 | 2 | 2 | 1 | 0 | 2 | 1 | 2 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 3 | 3 | 0 | 0 | 1 | 0 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 0 | 2 | 1 | 1 | 1 | 0 | 1 | 2 | 2 | 1 | 1 | 2 | 2 | 1 | 0 | 1 | 2 | 0 | 2 | 1 |
Number of Participants With Laboratory Abnormalities - Phase 2
"The number of participants with an on-study laboratory abnormality, assessed from Grade 1-4 Serum Chemistry, Electrolytes, and Hematology Laboratory Test results, with grade 4 being the worst.~Safety data are evaluated for laboratory abnormalities, defined and evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)." (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Participants (Number) |
|---|
| ALANINE AMINOTRANSFERASE (ALT), grade 1 | ALANINE AMINOTRANSFERASE (ALT), grade 2 | ALANINE AMINOTRANSFERASE (ALT), grade 3 | ALKALINE PHOSPHATASE (ALP), grade 1 | ALKALINE PHOSPHATASE (ALP), grade 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 1 | ASPARTATE AMINOTRANSFERASE (AST), grade 2 | ASPARTATE AMINOTRANSFERASE (AST), grade 3 | BILIRUBIN, TOTAL, grade 1 | BILIRUBIN, TOTAL, grade 2 | BILIRUBIN, TOTAL, grade 3 | CREATININE, grade 1 | CREATININE, grade 2 | CALCIUM, TOTAL, grade 1 | CALCIUM, TOTAL, grade 2 | CALCIUM, TOTAL, grade 3 | PHOSPHORUS, INORGANIC, grade 1 | PHOSPHORUS, INORGANIC, grade 2 | PHOSPHORUS, INORGANIC, grade 3 | PHOSPHORUS, INORGANIC, grade 4 | POTASSIUM, SERUM, grade 1 | POTASSIUM, SERUM, grade 2 | POTASSIUM, SERUM, grade 3 | POTASSIUM, SERUM, grade 4 | SODIUM, SERUM, grade 1 | SODIUM, SERUM, grade 2 | SODIUM, SERUM, grade 3 | HEMOGLOBIN, grade 2 | HEMOGLOBIN, grade 3 | PLATELET COUNT, grade 2 | PLATELET COUNT, grade 3 | PLATELET COUNT, grade 4 | ABSOLUTE NEUTROPHIL COUNT, grade 1 | ABSOLUTE NEUTROPHIL COUNT, grade 2 | ABSOLUTE NEUTROPHIL COUNT, grade 3 | ABSOLUTE NEUTROPHIL COUNT, grade 4 | LEUKOCYTES, grade 1 | LEUKOCYTES, grade 2 | LEUKOCYTES, grade 3 | LEUKOCYTES, grade 4 | LYMPHOCYTES (ABSOLUTE), grade 1 | LYMPHOCYTES (ABSOLUTE), grade 2 | LYMPHOCYTES (ABSOLUTE), grade 3 | LYMPHOCYTES (ABSOLUTE), grade 4 | NEUTROPHILS (ABSOLUTE), grade 1 | NEUTROPHILS (ABSOLUTE), grade 2 | NEUTROPHILS (ABSOLUTE), grade 3 | NEUTROPHILS (ABSOLUTE), grade 4 |
|---|
| LDAC - Ph2 | 4 | 2 | 0 | 8 | 2 | 4 | 2 | 0 | 1 | 1 | 0 | 6 | 2 | 3 | 7 | 0 | 1 | 1 | 2 | 0 | 5 | 0 | 4 | 0 | 7 | 0 | 4 | 4 | 17 | 1 | 3 | 17 | 0 | 1 | 1 | 16 | 1 | 0 | 5 | 10 | 1 | 7 | 7 | 1 | 0 | 1 | 1 | 16 |
,| ULO 1000mg + LDAC - Ph2 | 5 | 1 | 2 | 3 | 5 | 8 | 0 | 1 | 2 | 3 | 0 | 5 | 2 | 3 | 5 | 1 | 0 | 2 | 0 | 1 | 3 | 1 | 2 | 1 | 3 | 1 | 3 | 4 | 10 | 0 | 1 | 13 | 1 | 1 | 0 | 10 | 0 | 4 | 4 | 1 | 4 | 1 | 0 | 0 | 0 | 2 | 0 | 10 |
,| ULO 800mg + LDAC - Ph2 | 5 | 0 | 2 | 9 | 1 | 7 | 1 | 0 | 3 | 4 | 1 | 7 | 5 | 7 | 5 | 0 | 0 | 3 | 2 | 0 | 4 | 0 | 1 | 1 | 9 | 0 | 0 | 2 | 22 | 0 | 1 | 23 | 2 | 0 | 3 | 18 | 3 | 3 | 6 | 8 | 3 | 7 | 5 | 0 | 1 | 1 | 3 | 18 |
Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Participants Treated With LDAC Only - Phase 2
"This phase 2 secondary endpoint was based on the rate of Complete Remission (CR/CRi) and rate of Overall Remission (OR=PR+CR +CRi) prior to the initiation of any alternative therapy (including any subsequent ulocuplumab 800 mg for participants in the LDAC alone arm). The phase 2 analysis was conducted after all participants had an opportunity for 6 months of follow-up.~Overall remission rate: CR + CRi, + PR confidence interval based on the Clopper and Pearson method.~CR = complete response CRi = complete response, incomplete blood count PR = partial remission" (NCT02305563)
Timeframe: From first dose until a minimum follow-up of up to 2 months
| Intervention | Percentage of participants (Number) |
|---|
| CR/CRi | Overall remission rate |
|---|
| LDAC - Ph2 | 25.0 | 25.0 |
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
| Intervention | µg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 4 Day 1 | Cycle 4 Day 8 | Cycle 5 Day 1 | Cycle 5 Day 8 |
|---|
| ULO 800mg + LDAC - Ph1 | 0.100 | 75.890 | 125.797 | 96.333 | 126.029 | 78.218 | 129.580 | 80.409 | 133.650 | 32.621 | 124.996 |
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
| Intervention | µg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 4 Day 1 | Cycle 4 Day 8 | Cycle 5 Day 1 | Cycle 5 Day 8 | Cycle 9 Day 1 |
|---|
| ULO 1000mg + LDAC - Ph2 | 0.100 | 17.766 | 61.250 | 103.322 | 143.724 | 153.871 | 82.033 | 212.793 | 77.095 | 224.703 | 202.552 | 187.930 |
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
| Intervention | µg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 3 Day 1 | Cycle 3 Day 8 | Cycle 4 Day 1 | Cycle 4 Day 8 | Cycle 5 Day 1 | Cycle 5 Day 8 | Cycle 9 Day 1 | EOT |
|---|
| ULO 800mg + LDAC - Ph2 | 0.100 | 10.321 | 37.263 | 30.916 | 48.421 | 13.905 | 37.602 | 4.012 | 116.657 | 4.558 | 34.783 | 35.144 | 0.100 |
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
| Intervention | µg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 1 Day 15 |
|---|
| LDAC - Ph2 | 0.100 | 39.609 | 175.315 |
Trough Observed Serum Concentration (Ctrough) - Phases 1 and 2
"The Pharmacokinetic (PK) parameters are assessed for ulocuplumab following study drug administration.~EOT = end of treatment~Measure type and method of dispersion are Geometric mean and %CV, respectively" (NCT02305563)
Timeframe: Days 1, 8, 15 for cycle 1; Days 8, 15 for cycle 2; Days 1, 8 for cycles 3-5; Day 1 every 4th cycle thereafter; EOT; 30 days post last dose (follow-up)
| Intervention | µg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 1 Day 15 | Cycle 2 Day 8 | Cycle 2 Day 15 | Cycle 3 Day 8 | Cycle 4 Day 8 | Cycle 5 Day 8 |
|---|
| ULO 600mg + LDAC - Ph1 | 0.100 | 5.308 | 21.748 | 41.630 | 72.104 | 85.993 | 112.048 | 102.751 |
5-year Overall Survival (OS)
Measured from date of registration to date of death due to any cause. Patients last known to be alive and are censored at date of last contact. (NCT01412879)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) | 81 |
| Arm 2: R-Bendamustine (Induction Therapy) | 79 |
Progression-Free Survival (PFS) at 2 Years
Disease progression is defined using the 2007 revised Cheson et al. criteria that is at least 50% increase in sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed, or >= 50% increase in greatest transverse diameter (GTD) of any nodal > 1 cm in shortest axis, or >= 50% increase in the SPD of other target measurable lesions over the smallest sum observed, any new bone marrow involvement, any new lesion, lymph node with long axis is > 1.5 cm or if both long and short axes are > 1 cm, PET positive if patients with no pretreatment PET scan or when PET scan was positive before therapy. Progression-free survival is measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. (NCT01412879)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) | 82 |
| Arm 2: R-Bendamustine (Induction Therapy) | 81 |
Response Rate (Complete and Partial Response)
Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site. (NCT01412879)
Timeframe: Up to 9 months
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) | 94.1 |
| Arm 2: R-Bendamustine (Induction Therapy) | 82.9 |
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. (NCT01412879)
Timeframe: Up to 8 months (Assessed at the beginning of each cycle of treatment, at restaging, and at post transplant.)
| Intervention | Participants (Number) |
|---|
| Acidosis | Adult respiratory distress syndrome | Alanine aminotransferase increased | Anemia | Anorexia | Arthralgia | Aspartate aminotransferase increased | Blood bilirubin increased | CD4 lymphocytes decreased | Catheter related infection | Dehydration | Device related infection | Diarrhea | Enterocolitis | Enterocolitis infectious | Epistaxis | Fatigue | Febrile neutropenia | Gallbladder infection | Hyperglycemia | Hypoalbuminemia | Hypocalcemia | Hypokalemia | Hypomagnesemia | Hyponatremia | Hypophosphatemia | Hypotension | Hypoxia | Infections and infestations - Other, specify | Infusion related reaction | Lung infection | Lymphocyte count decreased | Myalgia | Nausea | Neutrophil count decreased | Pain in extremity | Platelet count decreased | Pruritus | Rash maculo-papular | Rectal hemorrhage | Small intestinal obstruction | Sore throat | Syncope | Tumor pain | Urinary tract infection | Vascular access complication | Vomiting | White blood cell decreased |
|---|
| R-Bendamustine (Induction Therapy) | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 5 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 27 | 1 | 0 | 12 | 1 | 6 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 14 |
,| R-HCVAD/MTX/Ara-C (Induction Therapy) | 0 | 0 | 1 | 10 | 0 | 0 | 1 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 5 | 0 | 2 | 0 | 0 | 5 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 10 | 0 | 1 | 11 | 0 | 12 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 10 |
,| Stem Cell Transplant (Consolidation Therapy) | 1 | 1 | 0 | 9 | 1 | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 4 | 1 | 1 | 0 | 0 | 13 | 1 | 0 | 0 | 2 | 1 | 1 | 1 | 3 | 1 | 1 | 0 | 0 | 1 | 12 | 0 | 2 | 16 | 0 | 19 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 20 |
Complete Remission Plus CR With Incomplete Blood Count Recovery (CRi) Rate
"The percentage of participants who achieved a CR or CRi at any time point during the study per the modified IWG criteria for AML and investigator assessment.~CR: absolute neutrophil count (ANC) ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL~Participants who never achieved CR or CRi or had no IWG disease assessment were considered to be non-responders in the calculation of CR + CRi rate." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 53.7 |
Complete Remission Rate
"Complete remission (CR) rate is defined as the percentage of participants who achieved a complete remission at any time point during the study per the modified IWG criteria for AML and investigator assessment.~CR: absolute neutrophil count (ANC) ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~Participants who never achieved CR or had no IWG disease assessment were considered to be non-responders in the calculation of CR rate." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 25.6 |
Complete Remission With Partial Hematologic Recovery (CRh) Rate
"Complete remission with partial hematologic recovery is a derived response based on bone marrow blast and hematology laboratory values. CRh rate is defined as the percentage of participants who achieved CRh as the best response at any time point during the study.~A participant achieved a CRh when meeting the following criteria:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and~Peripheral blood platelet count of > 0.5 × 10^5 /µL and~A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection.~Participants who never achieved CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CRh rate." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 20.7 |
CR Plus CRh Rate by Initiation of Cycle 2
"CR + CRh rate by initiation of Cycle 2 is defined as the percentage of participants who achieved CR or CRh by initiation of Cycle 2 of study treatment.~CR: ANC ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and~Peripheral blood platelet count of > 0.5 × 10^5 /µL and~A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection.~Participants who never achieved CR/CRh or did not have disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRh rate by initiation of Cycle 2." (NCT02287233)
Timeframe: Cycle 2, Day 1
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 30.5 |
CR Plus CRh Rate
"CR + CRh rate is defined as the percentage of participants who achieved CR or CRh at any time point during the study.~CR: ANC ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and~Peripheral blood platelet count of > 0.5 × 10^5 /µL and~A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection.~Participants who never achieved CR/CRh or did not have disease assessment or hematology data were considered to be non-responders in the calculation of CR + CRh rate." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 46.3 |
CR Plus CRi Rate by Initiation of Cycle 2
"The percentage of participants who achieved a CR or CRi by initiation of Cycle 2 of study treatment per the modified IWG criteria for AML and investigator assessment.~CR: ANC ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRi: Lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.~Participants who never achieved CR or CRi or had no IWG disease assessment by initiation of Cycle 2 were considered to be non-responders in the calculation of CR + CRi rate by initiation of Cycle 2." (NCT02287233)
Timeframe: Cycle 2, Day 1
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 28.0 |
Duration of Complete Response
Duration of CR is defined as the time from date that a participant achieved CR to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the duration of CR analysis. (NCT02287233)
Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 14.8 |
Duration of CR Plus CRh
Duration of CR + CRh is defined as the time from date that a participant achieved CR or CRh to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRh was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis. (NCT02287233)
Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 11.0 |
Duration of CR Plus CRi
Duration of CR + CRi is defined as the time from the date that a participant achieved CR or CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CR + CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis. (NCT02287233)
Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 9.8 |
Duration of CRi
Duration of CRi is defined as the time from date that a participant achieved CRi to the first date of relapse, clinical disease progression or death due to disease progression, whichever occurred earliest. Duration of CRi was estimated using Kaplan-Meier methodology. If a participant was still responding at the data cutoff date, then the participant's data were censored at their last disease assessment date. Disease assessment data after the onset of any post-treatment therapy were not included in the analysis. (NCT02287233)
Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 4.7 |
Overall Response Rate
"Overall response rate (ORR) is defined as the percentage of participants who achieved a complete remission (CR), complete remission with incomplete marrow recovery (CRi), or partial remission (PR) per the International Working Group (IWG) for AML response criteria, per investigator assessment.~CR: absolute neutrophil count (ANC) ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, red blood cell (RBC) transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL.~PR: all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 54.9 |
Overall Survival (OS)
Overall survival is defined as the time from the date of first dose to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study drug, or after the participant discontinued study drug. OS was estimated using Kaplan-Meier methodology. Participants who were still alive were censored at the analysis date. (NCT02287233)
Timeframe: Median duration of follow-up was 44.5 months (range: 0.3 to 63.7)
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 9.7 |
Phase 1: Number of Participants With Dose-limiting Toxicities
Dose-limiting toxicities (DLTs) were determined during cycle 1 of the dose-escalation phase and defined as Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 grade 4 (life threatening requiring urgent intervention) or 5 (resulted in death) toxicity, excluding adverse events commonly caused by AML (eg, neutropenia, fever). Hematologic DLT was defined as failure of platelet recovery to 25 × 10^9/L or greater and absolute neutrophil count (ANC) to 0.5 × 10^9/L or greater within 14 days of the last dose of venetoclax in the absence of residual AML. (NCT02287233)
Timeframe: Up to 28 days (Cycle 1)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 0 |
| Phase 1: 800 mg Venetoclax + LDAC | 1 |
Time to Best Response of CR + CRi
"The time to the best response of CR + CRi is defined as the time from the first date of study drug to the best response of CR or CRi per the IWG AML response criteria assessed by the investigator.~CR: absolute neutrophil count (ANC) ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 2.8 |
Time to Best Response of CR Plus CRh
"The time to the best response of CR + CRh is defined as the time from the first date of study drug to the best response of CR or CRh.~CR: ANC ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and~Peripheral blood platelet count of > 0.5 × 10^5 /µL and~A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 2.6 |
Time to First Response of CR + CRi
"The time to the first response of CR + CRi is defined as the time from the first date of study drug to the first response of CR or CRi per the IWG AML response criteria assessed by the investigator.~CR: absolute neutrophil count (ANC) ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRi: lack of morphologic evidence of leukemia (blasts < 5%), and platelet counts < 10^5 /µL or ANC < 10^3 /µL." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 1.4 |
Time to First Response of CR Plus CRh
"The time to the first response of CR + CRh is defined as the time from the first date of study drug to the first response of CR or CRh.~CR: ANC ≥ 10^3 /µL, platelet counts ≥ 10^5 /µL, RBC transfusion independence (a period of at least 56 days with no RBC transfusion), and bone marrow with < 5% blasts.~CRh is a derived response based on bone marrow blast and hematology lab values. A participant achieved a CRh when meeting the following criteria:~Bone marrow with < 5% blasts and~Peripheral blood neutrophil count of > 0.5 × 10^3 /µL and~Peripheral blood platelet count of > 0.5 × 10^5 /µL and~A 1 week (≥ 7 days) platelet transfusion-free period prior to the hematology lab collection." (NCT02287233)
Timeframe: Response was assessed at Cycle 2, Day 1, Cycle 4, Day 1, and every 3 cycles thereafter; median duration of treatment was 4.2 months.
| Intervention | months (Median) |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 1.0 |
Duration of Post Baseline Transfusion Independence
"The duration of transfusion independence is defined as the first time period that a participant received no RBC/platelet transfusions for at least 56 days during the evaluation period.~Post-baseline transfusion independence is defined as a period of at least 56 days with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier." (NCT02287233)
Timeframe: From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
| Intervention | days (Median) |
|---|
| Duration of RBC and platelet transfusion independence | Duration of RBC transfusion independence | Duration of platelet transfusion independence |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 150 | 123 | 155.5 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
"An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator rated the severity of each AE according to the CTCAE Version 4.0 and the following:~Grade 1: The AE is transient and easily tolerated (mild).~Grade 2: The AE causes discomfort and interrupts usual activities (moderate).~Grade 3: The AE causes considerable interference with usual activities and may be incapacitating (moderate to severe).~Grade 4: The AE is life threatening requiring urgent intervention.~Grade 5: The AE resulted in death.~The investigator assessed each event as either having a reasonable possibility or no reasonable possibility of being related to the use of study drug.~Treatment-emergent events are defined as events that began or worsened in severity after the first dose of study drug." (NCT02287233)
Timeframe: From first dose of study drug until 30 days after last dose of study drug; median (minimum, maximum) duration of treatment was 4.1 (0.2, 62.8) months overall.
| Intervention | Participants (Count of Participants) |
|---|
| Any treatment-emergent adverse event (TEAE) | TEAE with CTCAE Grade 3 or 4 | TEAE with CTCAE Grade 3 or above | Venetoclax-related TEAE | LDAC-related TEAE | TEAE leading to hospitalization | TEAE leading to venetoclax discontinuation | TEAE leading to LDAC discontinuation | TEAE leading to venetoclax interruption | TEAE leading to LDAC interruption | TEAE leading to venetoclax reduction | TEAE leading to LDAC reduction | TEAE leading to death |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 8 | 8 | 8 | 8 | 8 | 7 | 3 | 3 | 3 | 3 | 0 | 0 | 1 |
,| Phase 1: 800 mg Venetoclax + LDAC | 10 | 10 | 10 | 9 | 9 | 8 | 5 | 5 | 4 | 3 | 1 | 0 | 4 |
,| Phase 2: 600 mg Venetoclax + LDAC | 74 | 72 | 72 | 66 | 71 | 64 | 24 | 26 | 45 | 38 | 6 | 1 | 15 |
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to 24 Hours (AUC0-24) of Venetoclax
(NCT02287233)
Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
| Intervention | µg*h/mL (Mean) |
|---|
| Cycle 1, Day 10 (Venetoclax with LDAC) | Cycle 1, Day 18 (Venetoclax Alone) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 33.3 | 51.8 |
,| Phase 1: 800 mg Venetoclax + LDAC | 33.4 | 35.4 |
Phase 1: Area Under the Plasma Concentration-Time Curve Over Time From 0 to Last Measurable Concentration (AUCt) of Cytarabine
(NCT02287233)
Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
| Intervention | ng*h/mL (Mean) |
|---|
| Cycle 1, Day 1 (LDAC Alone) | Cycle 1, Day 10 (LDAC with Venetoclax) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 194 | 231 |
,| Phase 1: 800 mg Venetoclax + LDAC | 204 | 202 |
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Cytarabine
The highest concentration that a drug achieves in the blood after administration in a dosing interval. (NCT02287233)
Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1, Day 1 (LDAC Alone) | Cycle 1, Day 10 (LDAC with Venetoclax) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 175 | 166 |
,| Phase 1: 800 mg Venetoclax + LDAC | 174 | 175 |
Phase 1: Maximum Observed Plasma Concentration (Cmax) of Venetoclax
The highest concentration that a drug achieves in the blood after administration in a dosing interval. (NCT02287233)
Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
| Intervention | µg/mL (Mean) |
|---|
| Cycle 1, Day 10 (Venetoclax with LDAC) | Cycle 1, Day 18 (Venetoclax alone) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 2.04 | 2.92 |
,| Phase 1: 800 mg Venetoclax + LDAC | 2.26 | 2.36 |
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Cytarabine
The time at which the maximum plasma concentration (Cmax) is observed. (NCT02287233)
Timeframe: Cycle 1, Day 1 and Day 10 at pre-dose and at 15 and 30 minutes and 1, 3, 6 hours post-dose.
| Intervention | hours (Median) |
|---|
| Cycle 1, Day 1 (LDAC Alone) | Cycle 1, Day 10 (LDAC with Venetoclax) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 0.3 | 0.3 |
,| Phase 1: 800 mg Venetoclax + LDAC | 0.3 | 0.3 |
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax
The time at which the maximum plasma concentration (Cmax) is observed. (NCT02287233)
Timeframe: Cycle 1, Day 10 at predose and 2, 4, 6, 8, and 24 hours postdose (venetoclax with LDAC); Cycle 1, Day 18 at predose, 2, 4, 6, 8, and 24 hours postdose (venetoclax alone)
| Intervention | hours (Median) |
|---|
| Cycle 1, Day 10 (Venetoclax with LDAC) | Cycle 1, Day 18 (Venetoclax Alone) |
|---|
| Phase 1: 600 mg Venetoclax + LDAC | 4.0 | 7.0 |
,| Phase 1: 800 mg Venetoclax + LDAC | 8.0 | 6.6 |
Post Baseline Transfusion Independence Rate Among Participants Transfusion-dependent at Baseline
"Post baseline transfusion independence rate was estimated as the percentage of participants who achieved transfusion independence during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days (≥ 56 days) with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.~Results are reported for participants who achieved both RBC and platelet transfusion independence and for participants who received RBC transfusion independence and platelet transfusion independence." (NCT02287233)
Timeframe: From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| RBC and platelet transfusion independence | RBC transfusion independence | Platelet transfusion independence |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 45.0 | 45.3 | 60.9 |
Post Baseline Transfusion Independence Rate
"Post baseline transfusion independence rate was estimated as the percentage of participants who achieved transfusion independence during the evaluation period. Post-baseline transfusion independence is defined as a period of at least 56 days (≥ 56 days) with no RBC or platelet transfusion during the evaluation period. The evaluation period is from the first dose of study drug to the last dose of study drug until the 30 day follow-up visit, disease progression (including clinical progression), or death, whichever was earlier.~Results are reported for participants who achieved both RBC and platelet transfusion independence and for participants who received RBC transfusion independence and platelet transfusion independence." (NCT02287233)
Timeframe: From the first dose of study drug to the last dose of study drug plus 30 days, disease progression (including clinical progression), or death, whichever was earlier; median duration of treatment was 4.2 months.
| Intervention | percentage of participants (Number) |
|---|
| RBC and platelet transfusion independence | RBC transfusion independence | Platelet transfusion independence |
|---|
| Phase 1+2: 600 mg Venetoclax + LDAC | 45.1 | 47.6 | 58.5 |
Median Overall Survival (OS)
Overall Survival is defined as the time from randomization until death from any cause. (NCT00955916)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| CLAG Regimen With Gleevec® | 4.9 |
Median Progression Free Survival (PFS)
Progression Free Survival is defined as the duration of time from start of treatment to time of progression. Leukemia related failure (progressive disease): Failure to induce bone marrow hypoplasia after 2 cycles or regrowth of leukemic blasts ≥ 20%. (NCT00955916)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| CLAG Regimen With Gleevec® | 11.1 |
Overall Response Rate (ORR)
Overall Response Rate: Morphologic Complete Remission (CR) + Morphologic Complete Remission with incomplete blood count recovery (CRi) for evaluable participants. CR - Bone Marrow: < 5% blasts without Auer rods with at least 20% cellularity with maturation of all cell lines, No presence of unique phenotype by flow cytometry identical to what was found in the pretreatment specimen, No persistent dysplasia; Peripheral: normal blood counts, absolute neutrophil count (ANC) > 1.0 k/μl and platelets > 100 k/μl ANC > 1.0 k/μl and platelets > 100 k/μl (Peripheral blood counts documenting recovery can be utilized within 4 weeks of the bone marrow); No evidence of extramedullary leukemia. CRi - All CR criteria are met except for residual Neutropenia <1.0 x 10^9/L platelets < 100 k/μl. (NCT00955916)
Timeframe: 8 weeks per participant
| Intervention | percentage of participants (Number) |
|---|
| CLAG Regimen With Gleevec® | 37 |
1 Year Overall Survival Rate
The percentage of participants alive at one year (NCT02560025)
Timeframe: 1 Year
| Intervention | percentage of participants (Number) |
|---|
| Alisertib / MLN8237 | 50 |
Median Duration of Remission
"The median amount of time from first achieving remission to disease progression (with patients censored at death).~Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR.~Complete remission with incomplete blood count recovery (CRi): Same as CR but without achievement of specified ANC and/or platelet count~Recurrence/ morphologic relapse: reappearance of leukemic blasts in the peripheral blood or >5% blasts in the bone marrow not attributable to any other cause" (NCT02560025)
Timeframe: From the time of first remission to disease progression or death, median duration of 12.8 months
| Intervention | Months (Median) |
|---|
| Alisertib / MLN8237 | 12.8 |
Median Relapse Free Survival
"The median amount of time from achieving a complete remission to the first of disease recurrence or death. RFS applies only to the subset of patients who achieve a CR+CRi at the end of induction therapy.~Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR.~Complete remission with incomplete blood count recovery (CRi): Same as CR but without achievement of specified ANC and/or platelet count~Recurrence/ morphologic relapse: reappearance of leukemic blasts in the peripheral blood or >5% blasts in the bone marrow not attributable to any other cause" (NCT02560025)
Timeframe: From the time of treatment response until death or disease progression (up to about one year)
| Intervention | Months (Median) |
|---|
| Alisertib / MLN8237 | NA |
Number of Participants That Achieved Complete Remission With Incomplete Blood Count Recovery (CRi)
"The number of participants that achieved a best overall response of CRi while on study.~Complete Remission with Incomplete Blood Count Recovery (CRi): Same as for CR but without achievement of ANC at least 1000/uL (CRi) and/or platelet count of 100,000/uL (CRp)." (NCT02560025)
Timeframe: From the start of treatment until the end of study treatment, up to approximately 10 months
| Intervention | Participants (Count of Participants) |
|---|
| Alisertib / MLN8237 | 5 |
Number of Participants That Achieved Complete Remission
"The number of participants that achieved a best overall response of complete remission while on study.~Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR." (NCT02560025)
Timeframe: From the start of treatment until the end of study treatment, up to approximately 10 months
| Intervention | Participants (Count of Participants) |
|---|
| Alisertib / MLN8237 | 20 |
Number of Participants With Serious Adverse Events
Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events were considered to be Serious Adverse Events (SAE) if they were grade 3 or greater and deemed to be possibly, probably, or definitely related to the study treatment. (NCT02560025)
Timeframe: From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months
| Intervention | Participants (Count of Participants) |
|---|
| Alisertib / MLN8237 | 27 |
Percentage of Treatment-related Mortality (TRM)
"Number of treatment related deaths divided by total number of patients during induction or reinduction therapy.~Presented as percentage" (NCT02553460)
Timeframe: At the end of reinduction (up to 5 months after start of therapy)
| Intervention | Participants (Count of Participants) |
|---|
| Stratum 1 | 1 |
Phase 1 and 2: Event-Free Survival
Event free survival is defined as the time from first dose of study drug to relapse from CR, death, or second malignancy for participants who achieved CR. CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (>) 1,000/ microliter platelet count of >100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. (NCT01853228)
Timeframe: From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months
| Intervention | days (Median) |
|---|
| Decitabine (Dacogen) + Cytarabine | 1 |
Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
TEAEs are defined as adverse events with onset or worsening on or after date of first dose of study treatment. An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. (NCT01853228)
Timeframe: Approximately 3 years 10 months
| Intervention | Participants (Count of Participants) |
|---|
| Decitabine (Dacogen) + Cytarabine | 17 |
Phase 1 and 2: Overall Survival (OS)
OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive. (NCT01853228)
Timeframe: From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months
| Intervention | months (Median) |
|---|
| Decitabine (Dacogen) + Cytarabine | 5.1 |
Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine
The maximum tolerated dose (MTD) for cytarabine was based on the number of participants experiencing a dose-limiting toxicity (DLT) by the end of Cycle 1. A non-hematological DLT was defined as: any Grade >=3 toxicity that persists for greater than (>) 5 days or any Grade 2 toxicity that persists for >7 days and that is intolerable to the participant. A hematological DLT was defined as Grade 4 neutropenia or thrombocytopenia due to a hypoplastic bone marrow at Day 42, in the absence of malignant infiltration. The nominal duration of each cycle was 28 days. However, participants who had not experienced bone marrow recovery at Day 28 were followed up to Day 42. Failure of marrow recovery (improvement to Grade 3) by Day 42 was considered a DLT. The maximum duration of Cycle 1 was therefore 42 days. (NCT01853228)
Timeframe: Cycle 1 (42 days)
| Intervention | gram per square meter (Number) |
|---|
| Decitabine (Dacogen) + Cytarabine | 2 |
Phase 2: Overall Response Rate
Overall response rate is defined as percentage of participants with complete remission (CR) +complete remission with incomplete blood count recovery (CRi)+partial remission (PR) per IWG Criteria. CRi: morphologic CR with residual neutropenia (less than [<] 1,000/microliter) or thrombocytopenia <100,000/microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (>) 1,000/ microliter platelet count of >100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. PR: all the same hematologic values of a CR, but with a decrease of >=50% of the percentage of blasts to 5% to 25% in the bone marrow aspirate. (NCT01853228)
Timeframe: Up to approximately 3 years 10 months
| Intervention | Percentage of participants (Number) |
|---|
| Decitabine (Dacogen) + Cytarabine | 37.5 |
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28
Response rate (percentage of participants who achieved CR or CRi) was measured using international working group (IWG) criteria. Response rate is defined as complete remission (CR) or complete remission with incomplete blood count recovery (CRi) in children with relapsed or refractory acute myeloid leukemia. CRi is defined as morphologic CR with residual neutropenia (less than [<] 1,000/microliter) or thrombocytopenia <100,000/ microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (>) 1,000/ microliter, platelet count of >100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. (NCT01853228)
Timeframe: Cycle 1 (28 days) Day 28
| Intervention | percentage of participants (Number) |
|---|
| Decitabine (Dacogen) + Cytarabine | 20 |
Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28
Response rate (percentage of participants who achieved CR or CRi) was measured using international working group (IWG) criteria. Response rate is defined as complete remission (CR) or complete remission with incomplete blood count recovery (CRi) in children with relapsed or refractory acute myeloid leukemia. CRi is defined as morphologic CR with residual neutropenia (less than [<] 1,000/microliter) or thrombocytopenia <100,000/ microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (>) 1,000/ microliter, platelet count of >100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. (NCT01853228)
Timeframe: Cycle 2 (28 days) Day 28
| Intervention | percentage of participants (Number) |
|---|
| Decitabine (Dacogen) + Cytarabine | 66.7 |
Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment
Response rate (percentage of participants who achieved CR or CRi) was measured using international working group (IWG) criteria. Response rate is defined as complete remission (CR) or complete remission with incomplete blood count recovery (CRi) in children with relapsed or refractory acute myeloid leukemia. CRi is defined as morphologic CR with residual neutropenia (less than [<] 1,000/microliter) or thrombocytopenia <100,000/ microliter). CR is defined as morphologic leukemia-free state, with less than 5 percentage (%) blasts in aspirate sample with marrow spicules and with a count of greater than or equal to (>=) 200 nucleated cells, plus absolute neutrophil count (ANC) greater than (>) 1,000/ microliter, platelet count of >100,000/microliter and participant must be independent of transfusions for a minimum of 1 week before each marrow assessment. (NCT01853228)
Timeframe: End of study treatment (approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Decitabine (Dacogen) + Cytarabine | 12.5 |
Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine
AUC is the area under the plasma concentration-time curve of decitabine. (NCT01853228)
Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
| Intervention | nanogram*hour per milliliter (ng*h/mL) (Median) |
|---|
| > 1 month to <= 2 years | > 2 to <= 6 years | > 6 to <= 12 years | > 12 to <= 16 years |
|---|
| Decitabine (Dacogen) + Cytarabine | 124.8 | 131.5 | 158.9 | 162.4 |
Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine
Cmax is the maximum observed plasma concentration of Decitabine. (NCT01853228)
Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
| Intervention | nanogram per milliliter (ng/mL) (Median) |
|---|
| > 1 month to <= 2 years | > 2 to <= 6 years | > 6 to <= 12 years | > 12 to <= 16 years |
|---|
| Decitabine (Dacogen) + Cytarabine | 118.4 | 123.1 | 148.7 | 151.4 |
Phase 1 and 2: Total Clearance of Decitabine
Total clearance of drug after intravenously administration was calculated as: dose/area under the plasma concentration-time curve. (NCT01853228)
Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 minute (min), 0.5 hour, 1 hour, and 2 hour after end of infusion
| Intervention | liter per hour per square meter (Median) |
|---|
| >1 month to less than or equal to (<=) 2 years | Greater than (>) 2 to <= 6 years | > 6 to <= 12 years | > 12 to <= 16 years |
|---|
| Decitabine (Dacogen) + Cytarabine | 160.6 | 152.1 | 125.9 | 123.2 |
Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. (NCT01853228)
Timeframe: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
| Intervention | liter per square meter (Median) |
|---|
| > 1 month to <= 2 years | > 2 to <= 6 years | > 6 to <= 12 years | > 12 to <= 16 years |
|---|
| Decitabine (Dacogen) + Cytarabine | 35.9 | 36.5 | 31.8 | 35.9 |
Phase 2: Duration of Response
Duration of response is defined as weeks from date of first response to date of first relapse or date of death. (NCT01853228)
Timeframe: From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months
| Intervention | weeks (Number) |
|---|
| Participant 1 | Participant 2 |
|---|
| Decitabine (Dacogen) + Cytarabine | 44.6 | 6.3 |
Estimated Dose to Tumor Sites Based on the Tumor to Normal Organ Ratios Derived From Dosimetry Estimates Coupled With the Absorbed Dose to Normal Organs Based on the Administered Activity of Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Will be evaluated among all patients and among those treated at the estimated MTD. (NCT01921387)
Timeframe: Up to 5 years
| Intervention | mCi (Number) |
|---|
| Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) | 52.8 |
Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA
Single patients will be treated at escalating doses in 2-Gy increments (Table 4) until a DLT is observed. Once a DLT is observed, the second stage will begin at the next lower dose level and patients will be treated in cohorts of 4. (NCT01921387)
Timeframe: Within 30 days post-transplant
| Intervention | Gy - MTD (Number) |
|---|
| Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) | 34 |
Progression-free Survival Following Autologous Stem Cell Transplant (ASCT)
Estimate the 1 year progression-free survival (PFS) rate after ASCT (NCT01921387)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) | 12 |
The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients
(NCT01921387)
Timeframe: Up to 5 years
| Intervention | mg/kg (Number) |
|---|
| Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) | 0.75 |
Number of Participants With Infusion Reactions (IRs)
An IR was an AE related to isatuximab typically with onset within 24 hours from the start of the isatuximab infusion and was reported by the investigator. (NCT03860844)
Timeframe: From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort)
| Intervention | Participants (Count of Participants) |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 9 |
| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 5 |
| Acute Myeloid Leukemia (AML) | 15 |
Overall Response Rate (ORR)
ORR:Percentage of participants with CR/CRi or partial response (PR) for blood and bone marrow disease based on NCCN guideline. CR: <5% blasts in BMA with spicules; no circulating blasts (ALL)/no blasts with Auer rods (AML) or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement (ALL), trilineage hematopoiesis (ALL);ANC >=1000/mcL; platelets >100000/mcL; RBC transfusion independence. If the physician documented transfusion dependency related to study treatment;not to participant's underlying disease, CRi was reported. CRi met the same criteria as CR, except neutrophils and/or platelets recovery (ANC <1000/mcL or platelets <100000/mcL). PR: >50% decrease in the sum of the product of the greatest perpendicular diameters of the mediastinal enlargement. For participants with a previous positive positron emission tomography (PET) scan, a post-treatment PET was to be positive in at least 1 previously involved site. (NCT03860844)
Timeframe: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
| Intervention | percentage of participants (Number) |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 52.0 |
| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 54.5 |
| Acute Myeloid Leukemia (AML) | 65.2 |
Percentage of Participants With Complete Response (CR) Rate
The complete response rate (CR + CRi [complete response with incomplete peripheral recovery]) was defined as the percentage of participants achieving complete response (CR + CRi) assessed by the investigator per National Comprehensive Cancer Network (NCCN) guidelines version 1.2018 criteria. CR was defined as <5% blasts in a bone marrow aspirate (BMA) with spicules; no circulating blasts (ALL)/no blasts with Auer rods (AML) or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement (ALL), trilineage hematopoiesis (ALL); Absolute neutrophil count (ANC) >=1000/microliter (mcL); platelets >100000/mcL; red blood cell transfusion independence. If the physician documented transfusion dependency related to study treatment and not to the participant's underlying disease, CRi was reported. CRi met the same criteria as for CR, except neutrophils and/or platelets recovery (ANC <1000/mcL or platelets <100000/mcL). (NCT03860844)
Timeframe: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
| Intervention | percentage of participants (Number) |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 52.0 |
| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 45.5 |
| Acute Myeloid Leukemia (AML) | 60.9 |
AML: AUC of Isatuximab
Plasma samples were collected at specified timepoints to determine the AUC of isatuximab. (NCT03860844)
Timeframe: From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8
| Intervention | mg*h/L (Mean) |
|---|
| Week 0 to Week 1 | Week 0 to Week 3 | Week 0 to Week 8 |
|---|
| Acute Myeloid Leukemia (AML) | 28592 | 130862 | 291962 |
AML: Ceoi of Isatuximab
Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab. (NCT03860844)
Timeframe: At end of infusion on Cycle 1 Days 1 and 15
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1: Day 1 | Cycle 1: Day 15 |
|---|
| Acute Myeloid Leukemia (AML) | 363 | 562 |
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab. (NCT03860844)
Timeframe: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1: Day 8 | Cycle 1: Day 15 | Cycle 2: Day 1 | Cycle 2: Day 15 |
|---|
| Acute Myeloid Leukemia (AML) | 126 | 217 | 115 | 420 |
B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab
Plasma samples were collected at specified timepoints to determine the AUC of isatuximab. (NCT03860844)
Timeframe: From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10
| Intervention | mg*hour (h)/Liter (L) (Mean) |
|---|
| Week 0 to Week 1 | Week 0 to Week 5 | Week 0 to Week 10 |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 31703 | 299071 | 582686 |
,| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 29057 | 289167 | 540375 |
B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab
Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab. (NCT03860844)
Timeframe: At end of infusion on Cycle 1 Days 1 and 29
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1: Day 1 | Cycle 1: Day 29 |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 452 | 835 |
,| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 259 | 745 |
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab. (NCT03860844)
Timeframe: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 1 Day 29, Cycle 2 Day 43, Cycle 2 Day 57
| Intervention | microgram/milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1: Day 8 | Cycle 1: Day 15 | Cycle 1: Day 22 | Cycle 1: Day 29 | Cycle 2: Day 43 | Cycle 2: Day 57 |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 114 | 272 | 388 | 475 | 504 | 531 |
,| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 127 | 263 | 323 | 426 | 357 | 478 |
CD38 Receptor Occupancy
Blood samples were collected to assess CD38 receptor occupancy as a pharmacodynamics marker. It was assessed across complete responders and non-complete responders. Multicolor flow cytometry assay was validated for CD38 receptor occupancy (CD38RO) quantification, based on the use of two murine monoclonal antibodies (MAbs), one competing with SAR650984 to determine the number of free CD38 receptors (MAb1) and one recognizing a different binding epitope on CD38 to measure the total number of receptors (MAb2) at the cell surface of the cancer cells. Cells were tagged with either MAb1 (Tube #1) or MAb2 (Tube #2). The percentage RO was calculated using the following equation: % CD38RO = [(sABC MAb2 - sABC MAb1)/sABC MAb2] X 100. (NCT03860844)
Timeframe: Pre-dose on Day 15
| Intervention | percent receptor occupancy (Mean) |
|---|
| Blood plasma cells: Non CR/CRi; | Blood NK cells: CR/CRi | Blood NK cells: Non CR/CRi |
|---|
| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 44.0 | 55.6 | 61.3 |
CD38 Receptor Occupancy
Blood samples were collected to assess CD38 receptor occupancy as a pharmacodynamics marker. It was assessed across complete responders and non-complete responders. Multicolor flow cytometry assay was validated for CD38 receptor occupancy (CD38RO) quantification, based on the use of two murine monoclonal antibodies (MAbs), one competing with SAR650984 to determine the number of free CD38 receptors (MAb1) and one recognizing a different binding epitope on CD38 to measure the total number of receptors (MAb2) at the cell surface of the cancer cells. Cells were tagged with either MAb1 (Tube #1) or MAb2 (Tube #2). The percentage RO was calculated using the following equation: % CD38RO = [(sABC MAb2 - sABC MAb1)/sABC MAb2] X 100. (NCT03860844)
Timeframe: Pre-dose on Day 15
| Intervention | percent receptor occupancy (Mean) |
|---|
| Blood plasma cells: CR/CRi | Blood plasma cells: Non CR/CRi; | Blood NK cells: CR/CRi | Blood NK cells: Non CR/CRi |
|---|
| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 40.5 | 55.0 | 66.7 | 70.0 |
Cluster of Differentiation (CD)38 Receptor Density
"Blood samples were collected to assess CD38 receptor density as a predictive biomarker. It was assessed across complete responders and non-complete responders. The Antibody Binding Capacity (ABC) was calculated using the following equation: ABC = 10^(Logarithm(Mean Fluorescence Intensity)*a+b) where a was the slope and b was the Y-intercept of the calibration curve equation. Specific and absolute quantitative values (specific antibody-binding capacity [sABC]) of binding of the selected antibodies were calculated after subtraction of the negative isotypic immunoglobulin G (IgG) control." (NCT03860844)
Timeframe: Pre-dose on Day 1
| Intervention | sABC (Mean) |
|---|
| Blood blast cells: CR/CRi | Blood blast cells: Non CR/CRi; | Blood immune cells (Natural Killer [NK] cells): CR/CRi | Blood immune cells (NK cells): Non CR/CRi |
|---|
| Acute Myeloid Leukemia (AML) | 19502.0 | 9815.0 | 11220.3 | 22530.0 |
,| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 20345.6 | 31080.0 | 13506.2 | 16650.0 |
,| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 12780.0 | 22952.0 | 22639.0 | 33859.0 |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. SAEs were any untoward medical occurrence that at any dose: 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, was a medically important event. TEAEs were defined as an AE which occurred after the first dose of study treatment administration until the last dose plus 30 days, or until the start of hematological recovery period or a new anti-leukemia/lymphoma therapy, whichever occurred first. (NCT03860844)
Timeframe: From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any TESAE |
|---|
| Acute Myeloid Leukemia (AML) | 26 | 16 |
,| B-cell Acute Lymphoblastic Leukemia (B-ALL) | 27 | 19 |
,| T-cell Acute Lymphoblastic Leukemia (T-ALL) | 13 | 12 |
Minimal Residual Disease (MRD) Using Standardized Techniques
Percentage of participants with a CRMRD- response at the end of Cycle 1 (NCT03298984)
Timeframe: During duration of study
| Intervention | percentage of participants (Number) |
|---|
| Alvocidib 20/30 mg/m2 | 66.7 |
| Alvocidib 30/40 mg/m2 | 0 |
| Alvocidib 30/50 mg/m2 | 66.7 |
| Alvocidib 30/60 mg/m2 | 34.8 |
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) of Alvocidib
Determine the safety and tolerability including dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML (NCT03298984)
Timeframe: During the first cycle
| Intervention | Participants (Count of Participants) |
|---|
| Alvocidib 20/30 mg/m2 | 0 |
| Alvocidib 30/40 mg/m2 | 0 |
| Alvocidib 30/50 mg/m2 | 0 |
| Alvocidib 30/60 mg/m2 | 1 |
Antileukemic Activity of Alvocidib Plus 7+3 - Response to Treatment Based on 2017 ELN Response Criteria
CR: Measurable residual disease is positive or unknown; BM blasts (bls) <5%; no circulating bls and bls w/ Auer rods; no extramedullary disease; ANC >1.0 x 109/L; platelets >100 x 109/L. CRMRD-: CR w/ negativity genetic marker. CRi: CR except residual neutropenia or thrombocytopenia. MLFS: BM bls <5%; no bls with Auer rods; no extramedullary disease; no hematologic recovery required. PR: all hematologic CR criteria; decrease (dec) BM bls % to 5-25%; dec pretreatment BM bls % by >50%. SD: no CRMRD-/CR/CRi/PR/MLFS; PD criteria not met. PD: increase (inc) BM bls % and/or inc absolute bls in blood: 50% inc BM bls over baseline (>15% point inc required in cases w/ <30% bls at baseline or persistent BM bls % of >70% over at least 3 months; without at least 100% improvement in ANC to absolute level [>0.5 x 109/L and/or platelet count to >50 x 109/L non-transfused); or >50% inc in peripheral bls to >25 x 109/L (in the absence of differentiation syndrome); or new extramedullary disease. (NCT03298984)
Timeframe: Best response during duration of study
| Intervention | participants (Number) |
|---|
| Complete Remission MRD Negative (CRMRD-) | Complete Remission MRD Positive or Unknown (CR) | Partial Remission (PR) | Stable Disease | Progressive Disease (PD) | Not Evaluated |
|---|
| Alvocidib 20/30 mg/m2 | 2 | 1 | 0 | 0 | 0 | 0 |
,| Alvocidib 30/40 mg/m2 | 0 | 2 | 1 | 0 | 0 | 0 |
,| Alvocidib 30/50 mg/m2 | 2 | 0 | 0 | 0 | 1 | 0 |
,| Alvocidib 30/60 mg/m2 | 8 | 7 | 1 | 2 | 4 | 1 |
Maximum Tolerated Dose (MTD) of Alvocidib
Determine the safety and tolerability including the maximum tolerated dose (MTD) of alvocidib when administered over a range of doses on Days 1-3 followed by Ara-c/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML (NCT03298984)
Timeframe: During the first cycle
| Intervention | mg/m2 (Number) |
|---|
| Bolus | IV infusion |
|---|
| All Participants | 30 | 60 |
Recommended Phase 2 Dose (RP2D) of Alvocidib in Combination With 7+3
The dose at which < 1 of 6 patients experience a DLT during Cycle 1 with the next higher dose having at least 2 of 3 to 6 patients experiencing a DLT during Cycle 1 (NCT03298984)
Timeframe: During Cycle 1 beginning at 1st dose of study drug through Day 50 + or - 3 days
| Intervention | mg/m2 (Number) |
|---|
| Bolus | IV infusion |
|---|
| All Participants | 30 | 60 |
Change From Baseline in EQ-5D-5L Health Utility Index
The EQ-5D is a standardized instrument for use as a measure of health outcome. The descriptive system comprises 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort and Anxiety/Depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses from the 5 dimensions are coded so that a '1' indicates no problem on that dimension, and '5' indicates the most serious problem. Results obtained just prior to the start of study treatment on Day 1 of Cycle 1 will serve as the baseline values. If not available, the most recent screening results prior to the start of study treatment on Day 1 of Cycle 1 will be considered the baseline values. The responses for the 5 dimensions can be combined in a 5-digit number describing the respondent's health state. Score was converted to a single index value using the cross-walk method to the EQ-5D-3L value set. (NCT02577406)
Timeframe: From baseline up to cycle 2 day 1 (up to approximately 1 month)
| Intervention | Change from baseline in EQ-5D score (Mean) |
|---|
| AG-221 | -0.0738 |
| Conventional Care Regimens (CCRs) | -0.0598 |
Complete Remission Rate
The number of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML). CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease; plus the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. (NCT02577406)
Timeframe: From randomization up to approximately 49 months
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 11 |
| Conventional Care Regimens (CCRs) | 1 |
Duration of Response
Time from first documented MLFS/CR/CRi/CRp/PR to documented morphologic relapse after CR/CRi/CRp/ PD or death due to any cause, whichever occurs first. CR and MLFS are defined as <5% blasts in a BM aspirate sample with marrow spicules + a count of ≥200 nucleated cells with no blasts with Auer rods + no extramedullary disease. CR must also include: ANC ≥ 1,000/μL, Platelet count ≥100,000/μL, + independent of red cell transfusions for ≥1 week before assessment. CRi is all criteria of CR except ANC. CRp is all criteria of CR except platelet count. PR is defined as all hematologic criteria of CR with >50% decrease in BM blasts to 5%-25%. Relapse after CR/CRi/CRp is defined as reappearance of ≥ 5% blasts in the BM not attributable to other cause or development of extramedullary disease. PD is defined as > 50% increase of BM blast count from baseline to ≥ 20% or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10,000/μL or development of new extramedullary disease. (NCT02577406)
Timeframe: From randomization to documented morphologic relapse after CR/CRi/CRp/ PD or death due to any cause, whichever occurs first (up to approximately 49 months)
| Intervention | Months (Median) |
|---|
| AG-221 | 3.9 |
| Conventional Care Regimens (CCRs) | 4.5 |
Event-Free Survival
Time from randomization to documented morphologic relapse after complete remission/complete remission with incomplete neutrophil recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp), progressive disease (PD) or death from any cause, whichever occurs first. Morphologic Relapse after CR/CRi/CRp is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. PD is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease. (NCT02577406)
Timeframe: From randomization to the date of documented morphologic relapse after CR/CRi/CRp, PD or death from any cause, whichever occurs first. (up to approximately 49 months)
| Intervention | Months (Median) |
|---|
| AG-221 | 3.2 |
| Conventional Care Regimens (CCRs) | 2.5 |
Hematologic Improvement Rate
The number of participants with hematologic improvement neutrophil response (HI-N) + hematologic improvement platelet response (HI-P) + hematologic improvement erythroid response (HI-E) according to the International Working Group for Myelodysplastic Syndromes for Hematologic Improvement (IWG MDS HI) criteria. HI-E is defined as a hemoglobin increase by ≥ 1.5 g/dL and a relevant reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. HI-P is defined as an absolute increase of ≥ 30 X 10^9/L for participants starting with > 20 X and an increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-N is defined as At least 100% increase and an absolute increase > 0.5 X 10^9/L. (NCT02577406)
Timeframe: From randomization up to approximately 49 months
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 33 |
| Conventional Care Regimens (CCRs) | 9 |
One-Year Survival Rate
The proportion of participants alive at 1 year after randomization (NCT02577406)
Timeframe: From randomization to 1 year after randomization
| Intervention | Proportion of participants (Number) |
|---|
| AG-221 | 0.375 |
| Conventional Care Regimens (CCRs) | 0.261 |
Overall Remission Rate
The number of participants with CR + CRi + CRp according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete remission (CR) is defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. (NCT02577406)
Timeframe: From randomization up to approximately 49 months
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 17 |
| Conventional Care Regimens (CCRs) | 7 |
Overall Response Rate
Number of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present). (NCT02577406)
Timeframe: From randomization up to approximately 49 months
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 25 |
| Conventional Care Regimens (CCRs) | 7 |
Overall Survival (OS)
The time between randomization and death from any cause. Participants who drop-out or are alive at the end of trial will have their OS times censored at the time of last contact, as appropriate. (NCT02577406)
Timeframe: From randomization to death due to any cause (up to approximately 49 months)
| Intervention | Months (Mean) |
|---|
| AG-221 | 6.5 |
| Conventional Care Regimens (CCRs) | 6.2 |
The Number of Participants That Underwent Hematopoietic Stem Cell Transplantation (HSCT)
The number of participants that underwent hematopoietic stem cell transplantation during the study. (NCT02577406)
Timeframe: From randomization up to approximately 49 months
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 7 |
| Conventional Care Regimens (CCRs) | 2 |
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Hematology
The percent of participants with clinically significant hematology laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The hematology panel includes complete blood count (CBC) with differential, including red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count (with differential), absolute neutrophil count (ANC) and platelet count. (NCT02577406)
Timeframe: From first dose up to approximately 49 months
| Intervention | Percent of Participants (Number) |
|---|
| AG-221 | 94.3 |
| Conventional Care Regimens (CCRs) | 89.4 |
The Percent of Participants Experiencing Clinically Significant Laboratory Abnormalities - Serum Chemistry
The percent of participants with clinically significant serum chemistry laboratory abnormalities. A clinically significant laboratory abnormality is defined as meeting Grade 3 or Grade 4 criteria according to the Common Terminology Criteria for Adverse Events (CTCAE). Grade 3 is defined as severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. The chemistry panel includes sodium, potassium, calcium, magnesium, chloride, phosphorus, CO2, bicarbonate, blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, alkaline phosphatase (ALP), bilirubin (total and direct), uric acid, lactate dehydrogenase (LDH), AST/SGOT, ALT/SGPT, gamma glutamyl transpeptidase (GGT), amylase and lipase. (NCT02577406)
Timeframe: From first dose up to approximately 49 months
| Intervention | Percent of Participants (Number) |
|---|
| AG-221 | 42.7 |
| Conventional Care Regimens (CCRs) | 21.3 |
The Percent of Participants Experiencing Clinically Significant Vital Sign Abnormalities
The percent of participants with clinically significant vital sign abnormalities including weight, temperature, blood pressure, pulse rate, and respiratory rate. (NCT02577406)
Timeframe: From first dose up to approximately 49 months
| Intervention | Percent of Participants (Number) |
|---|
| AG-221 | 0 |
| Conventional Care Regimens (CCRs) | 0 |
The Percentage of Participants Experiencing Clinically Significant Electrocardiogram (ECG) Abnormalities
The percent of participants with clinically significant ECG abnormalities. 12-lead ECG was assessed by a physician trained in ECG interpretation. Intervals including PR, QRS, QT and RR were collected, as well as heart rate and rhythm. (NCT02577406)
Timeframe: From first dose up to approximately 49 months
| Intervention | Percentage of Participants (Number) |
|---|
| AG-221 | 7.6 |
| Conventional Care Regimens (CCRs) | 2.1 |
Time to Response
Time from randomization to first documented MLFS/CR/CRi/CRp/PR. Complete remission (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present). (NCT02577406)
Timeframe: From randomization to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 49 months)
| Intervention | Days (Median) |
|---|
| AG-221 | 58.0 |
| Conventional Care Regimens (CCRs) | 56.0 |
Time to Treatment Failure
Time from randomization to discontinuation of study treatment due to any cause (NCT02577406)
Timeframe: From randomization to discontinuation of study treatment due to any cause (up to approximately 49 months)
| Intervention | Months (Median) |
|---|
| AG-221 | 4.9 |
| Conventional Care Regimens (CCRs) | 1.9 |
Treatment Mortality at 30 Days
The number of participant deaths from any cause within 30 days of initiation of study treatment. (NCT02577406)
Timeframe: From first dose to 30 days after first dose
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 10 |
| Conventional Care Regimens (CCRs) | 13 |
Treatment Mortality at 60 Days
The number of participant deaths from any cause within 60 days of initiation of study treatment. (NCT02577406)
Timeframe: From first dose to 60 days after first dose
| Intervention | Participants (Count of Participants) |
|---|
| AG-221 | 27 |
| Conventional Care Regimens (CCRs) | 30 |
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)
The change from baseline in the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. A change of at least 10 points on the standardized domain scores was required for it to be considered meaningful. Results obtained just prior to the start of study treatment on Day 1 of Cycle 1 will serve as the baseline values. If not available, the most recent screening results prior to the start of study treatment on Day 1 of Cycle 1 will be considered the baseline values. (NCT02577406)
Timeframe: From baseline to cycle 2 day 1 (up to approximately 1 month)
| Intervention | Change from baseline in QLQ-C30 score (Mean) |
|---|
| Global QoL | Physical Functioning | Role Functioning | Cognitive Functioning | Emotional Functioning | Social Functioning | Fatigue | Nausea / Vomiting | Pain | Dyspnea | Insomnia | Appetite Loss | Constipation | Diarrhea | Financial Difficulties |
|---|
| AG-221 | -4.7 | -3.1 | -3.8 | -0.6 | 0.9 | -0.6 | 5.5 | 9.0 | 6.0 | -1.3 | 8.5 | 10.7 | 2.8 | 4.1 | -0.3 |
,| Conventional Care Regimens (CCRs) | -4.0 | -6.7 | -7.8 | -5.1 | -0.7 | -10.2 | 7.5 | 1.9 | 7.0 | 0.0 | 1.1 | 8.6 | 1.6 | 1.6 | -3.2 |
The Number of Participants Experiencing Adverse Events (AEs)
The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (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, or constitutes an important medical event. All AEs were coded using the MedDRA Version 22.0. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). A treatment-related TEAE was defined as a TEAE that was suspected by the investigator to be related to study treatment. The severity was graded by the study personnel based on NCI National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. (NCT02577406)
Timeframe: From first dose up to 28 days after last dose (up to approximately 49 months)
| Intervention | Participants (Count of Participants) |
|---|
| Treatment-Emergent Adverse Event (TEAE) | TEAE Related to Study Drug | Grade ≥ 3 TEAE | Grade ≥ 3 TEAE Related to Study Drug | Serious TEAE | Serious TEAE Related to Study Drug | TEAE Leading to Discontinuation of Study Drug | Treatment-related TEAE Leading to Discontinuation of Study Drug | TEAE Leading to Study Drug Dose Reduction Only | Treatment-related TEAE Leading to Study Drug Dose Reduction Only | TEAE Leading to Study Drug Dose Interruption Only | Treatment-related TEAE Leading to Study Drug Dose Interruption Only | TEAE Leading to Study Drug Dose Reduction or Dose Interruption | Treatment-related TEAE Leading to Study Drug Dose Reduction or Dose Interruption | TEAE Leading to Death | Treatment-related TEAE Leading to Death |
|---|
| AG-221 | 157 | 121 | 146 | 74 | 138 | 34 | 35 | 5 | 22 | 18 | 84 | 46 | 92 | 56 | 77 | 1 |
,| Conventional Care Regimens (CCRs) | 131 | 86 | 112 | 49 | 92 | 30 | 16 | 6 | 3 | 3 | 35 | 20 | 36 | 21 | 33 | 5 |
30-day All-cause Mortality
"As a summary of adverse events (captured on trial using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), 30-day all cause mortality is reported as a percent of patients treated at the MTD/RP2D.~Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors." (NCT03531918)
Timeframe: Up to 5 years. 30-day all-cause mortality is reported
| Intervention | proportion died on/before day 30 (Number) |
|---|
| GO3 Dose Level Includes Phase 1 and Phase 2 | .03 |
Maximum Tolerated Dose (MTD) of Gemtuzumab Ozogamicin (GO) When Added to GCLAM (Phase 1)
Defined as the highest dose studied in which the incidence of Dose Limiting Toxicity (DLT) is ≤33% (≤4 of 12 patients experiencing DLT), defined as any Grade 3 non-hematologic toxicity lasting >48 hours that results in >7-day delay of the subsequent treatment cycle, with the exception of febrile neutropenia or infection or toxicities secondary to febrile neutropenia or infection, or any Grade ≥4 non-hematologic toxicity except febrile neutropenia/infection (or toxicities secondary to febrile neutropenia or infection) unless felt to be a direct consequence of treatment-related toxicity (e.g. intestinal infection following mucosal barrier breakdown), and with the exception of constitutional symptoms if recovery to Grade ≤2 within 14 days. The National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 will be used. (NCT03531918)
Timeframe: At time of count recovery, second cycle of treatment, response assessment or removal from protocol (at approximately 1 month).
| Intervention | Participants (Count of Participants) |
|---|
| GO1 Dose Level Phase 1 | NA |
| GO3 Dose Level Includes Phase 1 and Phase 2 | NA |
Measurable Residual Disease (MRD) and Remission Rates: Alapasia (MRDneg)
"Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors.~o Aplasia rate is defined in this protocol as frequency of patients without blood count recovery after chemotherapy and bone marrow examination showing hypocellularity not meeting cellularity criteria for morphologic leukemia free state (MLFS). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry.~Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS.~Statistical significance tests were not performed." (NCT03531918)
Timeframe: 90 days
| Intervention | Participants (Count of Participants) |
|---|
| GO1 Dose Level Phase 1 | 0 |
| GO3 Dose Level Includes Phase 1 and Phase 2 | 2 |
Measurable Residual Disease (MRD) and Remission Rates: CR/CRi
"Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors.~Complete response (CR) + complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CR or CRi per the European LeukemiaNet 2017 criteria as defined above. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry.~Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS.~Statistical significance tests were not performed." (NCT03531918)
Timeframe: 90 days
| Intervention | Participants (Count of Participants) |
|---|
| GO1 Dose Level Phase 1 | 5 |
| GO3 Dose Level Includes Phase 1 and Phase 2 | 52 |
Measurable Residual Disease (MRD) and Remission Rates: CRi (MRDneg)
"Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors.~Complete response with incomplete hematologic recovery (CRi) rate is defined as the frequency of patients achieving CRi, which is defined by the European LeukemiaNet 2017 guidelines as all CR criteria except for residual neutropenia (ANC <1.0 x 109/L [1000/mL]) or thrombocytopenia (platelet count <100 x 109/L [100,000/mL]). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry.~Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS.~Statistical significance tests were not performed." (NCT03531918)
Timeframe: 90 days
| Intervention | Participants (Count of Participants) |
|---|
| GO1 Dose Level Phase 1 | 1 |
| GO3 Dose Level Includes Phase 1 and Phase 2 | 7 |
Measurable Residual Disease (MRD) and Remission Rates: MLFS (MRDneg)
"Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors.~Morphologic leukemia free state (MLFS) rate is defined as the frequency of patients achieving MLFS, which is defined by the European LeukemiaNet guidelines as bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. At least 200 cells should be enumerated or cellularity should be at least 10%. MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry.~Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS.~Statistical significance" (NCT03531918)
Timeframe: 90 days
| Intervention | Participants (Count of Participants) |
|---|
| GO1 Dose Level Phase 1 | 0 |
| GO3 Dose Level Includes Phase 1 and Phase 2 | 2 |
Overall Survival
OS was calculated for all participants and measured from initial trial therapy to death from any cause. Patients last known ot be alive were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. (NCT03531918)
Timeframe: 3 years and 1 month
| Intervention | percentage of participants (Number) |
|---|
| GO3 Dose Level | 60 |
Relapse-free Survival of GO3 Cohort
RFS was calculated for participants who achieved a complete remission (with or without count recovery; CR or CRi) and measured from the date remission to the first of relapse from CR/CRi or death from any cause. Patients last known to be alive in CR /CRi were censored at date of last contact. Will be estimated using the Kaplan-Meier method. Time to relapse will be estimated using non-parametric estimates of the cumulative incidence curve with death analyzed as a competing event. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors. (NCT03531918)
Timeframe: Up to 5 years. 2-year RFS reported.
| Intervention | percentage of participants (Number) |
|---|
| GO3 Dose Level Includes Phase 1 and Phase 2 | 51 |
Event-free Survival (EFS) Rate (Phase 2)
A two-stage design will be used to evaluate the EFS. Patients treated at the maximum tolerated dose (MTD) from the phase 1 portion of the trial will be used in the phase 2 analysis. If censoring occurs, secondary analyses analyzing 6-month or 1-year EFS accounting for censoring will be done, including estimating 6-month or 1-year EFS using the Kaplan-Meier method. The first stage of the two-stage phase 2 design will evaluate 30 patients. If 20 or more of the first 30 patients are alive without event at 6-months after study registration, an additional 30 patients will be enrolled. If 46 or more of the 60 patients treated at the MTD are alive and without event at 6-months after study registration, the study will consider the regimen of interest for further investigation. Patients last known to be alive in CR were censored at date of last contact. (NCT03531918)
Timeframe: From the start of study treatment, assessed at 6 months and 1 year
| Intervention | percent of participants (Number) |
|---|
| Event-free Survival (6 months) | Event-free survival (12 months) |
|---|
| GO3 Dose Level Includes Phase 1 and Phase 2 | 73 | 58 |
Measurable Residual Disease (MRD) Rates and Remission Rates: CR
"Will be estimated and 95% confidence intervals will be calculated. Regression models (logistic regression for binary endpoints, Cox regression for time-to-event endpoints [Cox models for the hazard of the subdistribution for events with competing risks]) will be used to compare outcomes with patients who have received GCLAM without GO at our institution, controlling for measured prognostic factors.~Complete response (CR) rate is defined as the frequency of patients achieving CR, which is defined by the European LeukemiaNet 2017 guidelines as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 x 109/L (1000/mL); platelet count ≥100 x 109/L. (100 000/mL). MRD negative (MRDneg) status is defined as negative for leukemic markers by multiparameter flow cytometry.~Aplasia was defined as absence of tumoral cells but cellularity not meeting criteria for MLFS.~Statistical significance tests were not performed." (NCT03531918)
Timeframe: 90 days
| Intervention | Participants (Count of Participants) |
|---|
| MRDneg | MRDpos |
|---|
| GO1 Dose Level Phase 1 | 4 | 0 |
,| GO3 Dose Level Includes Phase 1 and Phase 2 | 38 | 7 |
Maximum Tolerated Dose (MTD) Oxaliplatin
MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale. (NCT00452374)
Timeframe: From treatment onset to end of each cycle of treatment (every 21 days)
| Intervention | mg/m^2 (Number) |
|---|
| Oxaliplatin, Fludarabine, Cytarabine + Rituximab | 25 |
Number of Participants With a Complete Response or Partial Response
According to International Workshop Response Criteria for Non-Hodgkin's Lymphomas: Complete remission (CR) defined as > 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; and Partial remission (PR) defined as > 50% decrease of clinical symptoms from baseline and recovery from blood counts. (NCT00452374)
Timeframe: Evaluation every 3 cycles of treatment (28 days per cycle), approximately 90 days
| Intervention | Participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) |
|---|
| Oxaliplatin, Fludarabine, Cytarabine + Rituximab | 12 | 28 |
Overall Survival of Patients Over Age 60 With Newly Diagnosed AML/High Risk MDS
Compared to historical data of a completed Southwestern Oncology Group (SWOG) trial of azacitidine and gemtuzumab ozogamicin. (NCT02121418)
Timeframe: At 6 months
| Intervention | participants (Number) |
|---|
| Treatment (Decitabine, Cytarabine) | 7 |
Response Rate
Rate of Complete Response or Complete Response with Incomplete Count Recovery (NCT02121418)
Timeframe: Up to 2 years
| Intervention | participants (Number) |
|---|
| Complete Respnose | Complete Response with Incomplete Count Recovery |
|---|
| Treatment (Decitabine, Cytarabine) | 4 | 3 |
Median Overall Survival (OS) Time
OS was defined as the time from start of study drug to death from any cause. OS was estimated using Kaplan-Meier analysis. Participants alive at the last date known to be alive were censored for the analysis. (NCT01880437)
Timeframe: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
| Intervention | months (Median) |
|---|
| Poor Risk Cytogenetics | 3.38 |
| FLT-3 Mutation Positive | 1.43 |
| Neither Poor Risk Cytogenetics Nor FLT-3 | 3.65 |
Percentage of Participants With an Event of Death During the Study
(NCT01880437)
Timeframe: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
| Intervention | percentage of participants (Number) |
|---|
| Poor Risk Cytogenetics | 80.0 |
| FLT-3 Mutation Positive | 100.0 |
| Neither Poor Risk Cytogenetics Nor FLT-3 | 89.5 |
Duration of Overall Response (DOR)
DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria [CR or CRi or MLFS or PR] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug). (NCT01880437)
Timeframe: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
| Intervention | weeks (Median) |
|---|
| DOR of participants with CRi (n=0,0,1) | DOR of participants with PR (n=0,0,1) |
|---|
| Neither Poor Risk Cytogenetics Nor FLT3 | 13 | 6.1 |
Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method. (NCT01880437)
Timeframe: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
| Intervention | percentage of participants (Number) |
|---|
| CR | CRi | MLFS | PR |
|---|
| FLT-3 Mutation Positive | 0 | 0 | 0 | 0 |
,| Neither Poor Risk Cytogenetics Nor FLT3 | 0 | 6.3 | 0 | 6.3 |
,| Poor Risk Cytogenetics | 0 | 0 | 0 | 0 |
Complete Remission Rate (CR)
CR is calculated as the percentage of patients with complete remission after the therapy. The response criteria is based on International Working Group Criteria. Complete Remission: Neutrophils(cells/μl)>1000, Platelets (plt/μl)≥ 100,000,Bone marrow blasts (%) <5; CR with incomplete count recovery (CRi): meets criteria for CR except for neutrophils ≤1000 or Meets criteria for CR except for platelets< 100,000; Partial Remission: CR except for Bone marrow blasts (%) Decrease of ≥ 50% to value between 5% and 25%; Treatment Failure:Persistent acute myeloid leukemia in blood or bone marrow, or therapy fails to achieve a remission of any category, or death prior to response assessment (NCT02658487)
Timeframe: Up to 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Vosaroxin, Cytarabine) | 20 |
Event-free Survival
Survival distribution will be estimated using the method of Kaplan and Meier. Event-free survival time is defined as the time from start of therapy to progression or death for any reason (which ever comes first), and those alive without progression are censored at the last day of follow up. (NCT02658487)
Timeframe: From start of therapy up to 1 year
| Intervention | months (Median) |
|---|
| Treatment (Vosaroxin, Cytarabine) | 7.6 |
Frequency of Grade 3-5 Adverse Event Related to Cytarabine and Vosaroxin (7+V)
Events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Counts of all events are summed up. (NCT02658487)
Timeframe: Up to 3 months
| Intervention | adverse events (Number) |
|---|
| Treatment (Vosaroxin, Cytarabine) | 133 |
Leukemia-free Survival (LFS or DFS)
Survival distribution will be estimated using the method of Kaplan and Meier. LFS time is defined as the time from complete remission to disease progression or death for any reason and those disease free and alive are censored at the last day of follow up. (NCT02658487)
Timeframe: The time from complete remission to disease progression or death for any reason, assessed up to 1 year
| Intervention | months (Median) |
|---|
| Treatment (Vosaroxin, Cytarabine) | NA |
Overall Survival
Survival distribution will be estimated using the method of Kaplan and Meier. The overall survival time is defined as time from start of therapy to death of any reason. Those alive are censored at the last day of known alive. (NCT02658487)
Timeframe: The time from start of therapy to death, assessed up to 1 year
| Intervention | months (Median) |
|---|
| Treatment (Vosaroxin, Cytarabine) | 10.7 |
Rate of CR/CRi
"Frequency of Complete Remission / Complete Remission with Incomplete Count Recovery (CR/CRi) after 7+V induction and/or re-induction" (NCT02658487)
Timeframe: Up to 3 months
| Intervention | Proportion of participants (Number) |
|---|
| Treatment (Vosaroxin, Cytarabine) | 0.55 |
Event-free Survival
All randomized subjects were assessed for event-free survival (EFS). EFS was defined as the time from study randomization to the date of induction treatment failure (persistent disease), relapse from CR or CRi or death from any cause, whichever came first. Subjects alive and not known to have any of these events were censored on thee date they were last examined on study. (NCT01696084)
Timeframe: From the date of randomization to the date that persistent disease was documented or the date of relapse after CR or death, whichever came first
| Intervention | months (Median) |
|---|
| Arm A (CPX-351) | 2.53 |
| Arm B (7+3) | 1.31 |
Overall Survival
Overall survival was measured from the date of randomization to death from any cause, subjects not known to have died by the last follow-up were censored on the date they were last known to be alive. (NCT01696084)
Timeframe: From the date of randomization to death from any cause
| Intervention | months (Median) |
|---|
| Arm A (CPX-351) | 9.56 |
| Arm B (7+3) | 5.95 |
Proportion of Subjects Receiving a Stem Cell Transplant
The number and percentage of subjects transferred for HSCT after induction treatment was recorded. (NCT01696084)
Timeframe: Post Induction
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (CPX-351) | 52 |
| Arm B (7+3) | 39 |
Proportion of Subjects With a Response
Complete Remission (CR) (NCT01696084)
Timeframe: Post Induction
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (CPX-351) | 57 |
| Arm B (7+3) | 40 |
Rate of Achieving Morphologic Leukemia-free State
All randomized subjects with at least 1 evaluable postrandomization bone marrow assessment performed on or after Day 14 after the last induction were assessed for MLFS. (NCT01696084)
Timeframe: Day 14
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (CPX-351) | 87 |
| Arm B (7+3) | 66 |
Remission Duration
Only subjects achieving CR or CRi were assessed for remission duration. (NCT01696084)
Timeframe: From the date of achievement of a remission until the date of relapse or death from any cause
| Intervention | months (Median) |
|---|
| Arm A (CPX-351) | 6.93 |
| Arm B (7+3) | 6.11 |
Median Overall Survival (OS)
Overall Survival (OS), defined for those patients who have achieved CR or CRi as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, to be analyzed similarly. Descriptive analysis was planned for this measure. (NCT00831766)
Timeframe: Up to 24 Months
| Intervention | months (Median) |
|---|
| All Participants Treated at MTD | 11.22 |
Median Progression-Free Survival (PFS)
Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse, or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. (NCT00831766)
Timeframe: 24 months
| Intervention | months (Median) |
|---|
| All Participants Treated at MTD | 7.55 |
Phase I: Recommended Phase II Dose
For the Phase I component, no formal statistical analysis was planned. The primary endpoint is to determine the maximum tolerated dose (MTD) and recommended Phase II dose of lenalidomide given in combination with standard idarubicin + cytarabine induction therapy. (NCT00831766)
Timeframe: 18 months
| Intervention | mg/day (Number) |
|---|
| Phase I Participants | 20 |
Phase II: Complete Response Rate of Participants Treated at Maximum Tolerated Dose (MTD)
Percentage of participants achieving CR/CRi. Complete Response (CR) plus Complete Response with Incomplete Count Recovery (CRi) rates. Response rates (CR + CRi) of lenalidomide following idarubicin and cytarabine induction therapy in older patients with previously untreated AML. A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. CRi: After chemotherapy, patients fulfill all of the criteria for CR except for residual neutropenia (1,000/μL) or thrombocytopenia (100,000/μL). (NCT00831766)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| All Participants Treated at MTD | 54 |
Rate of Lenalidomide Related Toxicity During Maintenance Therapy
Rate of toxicities of lenalidomide as maintenance therapy according to the National Cancer Institute Common Toxicity Criteria (CTC) V3. Adverse Events: Possibly Related; Probably Related, or Definitely Related to study treatment. Events are categorized as Grade 1 or 2, or as Grade 3 or 4. (NCT00831766)
Timeframe: 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Leukocytes (total WBC) - low - Grade 1 or 2 | Leukocytes (total WBC) - low - Grade 3 or 4 | ANC/AGC - Grade 1 or 2 | ANC/AGC - Grade 3 or 4 | Platelets - low - Grade 1 or 2 | Platelets - low - Grade 3 or 4 | Fatigue - Grade 1 or 2 | Fatigue - Grade 3 or 4 | Dry skin - Grade 1 or 2 | Dry skin - Grade 3 or 4 | Pruritus/itching - Grade 1 or 2 | Pruritus/itching - Grade 3 or 4 | Rash/desquamation - Grade 1 or 2 | Rash/desquamation - Grade 3 or 4 | Constipation - Grade 1 or 2 | Constipation - Grade 3 or 4 | Diarrhea - Grade 1 or 2 | Diarrhea - Grade 3 or 4 | Nausea - Grade 1 or 2 | Nausea - Grade 3 or 4 | Ulcer, GI - Anus - Grade 1 or 2 | Ulcer, GI - Anus - Grade 3 or 4 | Hemorrhage, GI - Rectum - Grade 1 or 2 | Hemorrhage, GI - Rectum - Grade 3 or 4 | Infection - Skin (cellulitis) Grade 1 or 2 | Infection - Skin (cellulitis) Grade 3 or 4 | AST, SGOT - Grade 1 of 2 | AST, SGOT - Grade 3 or 4 | Pain - Head/headache - Grade 1 or 2 | Pain - Head/headache - Grade 3 or 4 |
|---|
| Maintenance Phase Participants | 1 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 |
Disease-free Survival
(NCT00863434)
Timeframe: Every 3 months for 2 years, and then annually for 3 years
| Intervention | months (Median) |
|---|
| Treatment (Colony Stimulating Factor and Chemotherapy) | 6.43 |
Minimal Residual Disease as Assessed by Bone Marrow Flow Cytometry
Percent of white blood cells that are blasts in the bone marrow post-treatment. (NCT00863434)
Timeframe: Post-treatment
| Intervention | percent of white blood cells (Median) |
|---|
| Treatment (Colony Stimulating Factor and Chemotherapy) | 1.8 |
Overall Survival
(NCT00863434)
Timeframe: Every 3 months for 2 years, and then annually for 3 years
| Intervention | months (Median) |
|---|
| Treatment (Colony Stimulating Factor and Chemotherapy) | 9.73 |
Relapse Free Survival
Percentage of participants alive and without relapsed disease at two years. (NCT01588951)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| No Leukemia Stem Cells - Consolidation | 0 |
| Leukemia Stem Cells - Consolidation | 0 |
| Leukemia Stem Cells - Transplant | 0 |
Overall Survival (OS) at 1 Year
(NCT00392834)
Timeframe: 1 year post treatment
| Intervention | Cumulative proportion surviving at 1 yr (Number) |
|---|
| Regimen A (R-CODOX-M Chemotherapy) | 1.0 |
| Regimen B (Rituximab and IVAC Chemotherapy) | 0.82 |
Complete Response
Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an Absolute Neutrophil Count of at least 1000/mililiter and a platelet count of 100,000 mililiter, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. A complete remission must be confirmed 4 to 6 weeks after the initial documentation. If possible, at least one bone marrow biopsy should be performed to confirm the complete remission. (NCT00407966)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Arm A | 45 |
Complete Response
Bone marrow showing less than 5% leukemic blasts with normal maturation of all cell lines, an ANC of at least 1000/uL and a platelet count of 100,000/uL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. Repeat marrow confirmation 4-6 weeks following the marrow documenting CR is not required due to the need for continued treatment in CR. (NCT00795002)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Arm I | 24 |
| Arm II | 29 |
Disease-free Survival
This will be defined as the time between study entry and the first date that recurrent or progressive disease is objectively documented, or death from any cause occurs. (NCT00795002)
Timeframe: up to 2 years
| Intervention | months (Median) |
|---|
| Arm I | 13.6 |
| Arm II | 12.0 |
Number of Participants Experiencing Death From Any Cause Within 60 Days of Starting FLAM
Toxicity defined as death from any cause within 60 days of starting FLAM. (NCT00795002)
Timeframe: 60 days
| Intervention | Participants (Count of Participants) |
|---|
| Arm I | 3 |
| Arm II | 3 |
Disease-free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse. (NCT01272245)
Timeframe: Up to 5 years after completion of active treatment and while on study. Participants may receive up to 24 courses of study medication.
| Intervention | Months (Median) |
|---|
| Omacetaxine and Cytarabine | 3.1 |
Evaluation of CR Duration
The date of Complete Response to the date of loss of response or last follow-up. (NCT01272245)
Timeframe: Up to 5 years after completion of active treatment and while on study. Participants may receive up to 24 courses of study medication.
| Intervention | Months (Median) |
|---|
| Omacetaxine and Cytarabine | 10.6 |
Induction Mortality
Death within 8 weeks from the start of treatment. (NCT01272245)
Timeframe: Up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Omacetaxine and Cytarabine | 4 |
Overall Survival
Time from date of treatment start until date of death due to any cause (NCT01272245)
Timeframe: Up to 5 years after completion of active treatment and while on study. Participants may receive up to 24 courses of study medication.
| Intervention | Months (Median) |
|---|
| Omacetaxine and Cytarabine | 8.1 |
Percentage of Participants With Complete Remission (CR)
Complete response (CR) defined as: Peripheral blood counts, no circulating blasts, neutrophil count ≥ 1.0 ×109/L, platelet count ≥ 100 ×109/L, bone marrow aspirate and biopsy, ≤5% blasts, no detectable auer rods, no extramedulary leukemia (NCT01272245)
Timeframe: Up to 4 months
| Intervention | percentage of participants (Number) |
|---|
| Omacetaxine and Cytarabine | 44 |
Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy
approximate time: at the recovery of cytopenia (NCT00844298)
Timeframe: 1 month
| Intervention | percentage of analyzable subjects (Number) |
|---|
| Nilotinib+mVPD | 91 |
Complete Response (CR) Rate
"To compare the complete response rate between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.~Complete response is defined as: ANC >= 1,000/mcl, platelet count >= 100,000/mcl, < 5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease (no requirements for marrow cellularity or hemoglobin concentration)" (NCT01802333)
Timeframe: Up to 5 years
| Intervention | Percentage of participants (Number) |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 75 |
| Arm II (High-dose Cytarabine, Idarubicin) | 80 |
| Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) | 77 |
Disease-free Survival (DFS) Among High Risk Patients
"DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery). DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.~2-year DFS for high risk patients will be estimated using the Kaplan-Meier method." (NCT01802333)
Timeframe: DFS assessed for up to 5 years, 2 year DFS reported
| Intervention | Proportion of participants (Number) |
|---|
| High Risk Patients | 0.30 |
Disease-free Survival (DFS)
"To compare the disease-free survival (DFS) between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.~DFS is calculated for patients who have achieved a CR or CRi (complete response with incomplete blood count recovery) . DFS will be measured from the date of CR or CRi until relapse from CR or CRi for death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive without report of relapse.~2-year DFS by arm will be estimated using the Kaplan-Meier method." (NCT01802333)
Timeframe: DFS assessed for up to 5 years, 2 year DFS reported
| Intervention | Proportion of participants (Number) |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 0.48 |
| Arm II (High-dose Cytarabine, Idarubicin) | 0.51 |
| Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) | 0.46 |
EFS of Arm I Compared to Arm II
"EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.~A two-sided test of the hazard ratio (HR) of 7:3: IA (versus the null hypothesis of HR =1) will be done using a proportional hazards regression model with the stratification factors included as covariates.~2-year EFS by arm will be estimated using the Kaplan-Meier method." (NCT01802333)
Timeframe: EFS assessed for up to 5 years, 2 year EFS reported
| Intervention | Proportion of participants (Number) |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 0.36 |
| Arm II (High-dose Cytarabine, Idarubicin) | 0.41 |
Event-free Survival (EFS)
"EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi.~2-year EFS by arm will be estimated using the Kaplan-Meier method. EFS will be compared between Arm I and Arm III and between Arm II and Arm III using Cox proportional hazards regression." (NCT01802333)
Timeframe: EFS assessed for up to 5 years, 2 year EFS reported
| Intervention | Proportion of participants (Number) |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 0.36 |
| Arm II (High-dose Cytarabine, Idarubicin) | 0.41 |
| Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) | 0.37 |
Overall Survival (OS)
"To compare OS between patients who receive standard 7+3 therapy or IA to patients who receive IA + vorinostat.~OS is calculated for all patients from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.~2-year OS by arm will be estimated using the Kaplan-Meier method." (NCT01802333)
Timeframe: OS assessed for up to 5 years, 2 year OS reported
| Intervention | Proportion of participants (Number) |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 0.56 |
| Arm II (High-dose Cytarabine, Idarubicin) | 0.59 |
| Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) | 0.58 |
Prevalence of the Mutation NPM1 in Patients on This Study.
To estimate the prevalence of the mutation NPM1 in this patient population. (NCT01802333)
Timeframe: Baseline
| Intervention | percentage of patients (Number) |
|---|
| All Arms Combined | 33 |
Rate of Allogeneic HCT
The goal of the transplant objective is to determine whether it is possible to conduct allogeneic HCT on 60% or more of adults with high-risk AML in first complete remission (alternative). If 40% or fewer of high-risk patients in CR can be transplanted, the proposed transplant support system will not be considered feasible. A one-sided binomial test compared to the null transplant rate will be conducted. (NCT01802333)
Timeframe: Up to 5 years
| Intervention | percentage of patients (Number) |
|---|
| High Risk Patients in First Complete Remission | 65 |
Cytogenetic Risk Distribution of Patients on This Study
To estimate the cytogenetic risk distribution of patients on this study. (NCT01802333)
Timeframe: Baseline
| Intervention | percentage of participants (Number) |
|---|
| High risk | Intermediate risk | Low risk |
|---|
| All Arms Combined | 22.3 | 64.2 | 13.5 |
Frequency and Severity of Toxicities
Number of patients with Grade 3-5 adverse events that were possibly, probably or definitely related to study drug are reported by given type of adverse event. (NCT01802333)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Abdominal distension | Abdominal infection | Abdominal pain | Acidosis | Acute kidney injury | Adult respiratory distress syndrome | Alanine aminotransferase increased | Alkaline phosphatase increased | Alkalosis | Allergic reaction | Anal hemorrhage | Anal pain | Anal ulcer | Anemia | Anorectal infection | Anorexia | Aspartate aminotransferase increased | Atelectasis | Atrial fibrillation | Atrial flutter | Atrioventricular block complete | Blood and lymphatic system disorders - Other | Blood bilirubin increased | Bone infection | Bone pain | Bronchopulmonary hemorrhage | Bullous dermatitis | CD4 lymphocytes decreased | Cardiac arrest | Cardiac disorders - Other, specify | Cardiac troponin I increased | Catheter related infection | Chills | Chronic kidney disease | Cognitive disturbance | Colitis | Colonic hemorrhage | Colonic perforation | Conduction disorder | Confusion | Conjunctivitis | Constipation | Constrictive pericarditis | Creatinine increased | Death NOS | Dehydration | Dental caries | Device related infection | Diarrhea | Disseminated intravascular coagulation | Dry mouth | Dry skin | Duodenal hemorrhage | Dyspepsia | Dysphagia | Dyspnea | Edema cerebral | Edema limbs | Ejection fraction decreased | Electrocardiogram QT corrected interval prolonged | Encephalopathy | Enterocolitis | Enterocolitis infectious | Epistaxis | Erythema multiforme | Erythroderma | Esophageal hemorrhage | Esophageal pain | Esophagitis | Eye infection | Fatigue | Febrile neutropenia | Fever | GGT increased | Gait disturbance | Gastric hemorrhage | Gastritis | Gastroesophageal reflux disease | Gastrointestinal disorders - Other, specify | General disorders and admin site conditions-Other | Generalized muscle weakness | Genital edema | Glucose intolerance | Gum infection | Headache | Heart failure | Hematoma | Hematuria | Hepatic failure | Hepatic infection | Hepatobiliary disorders - Other, specify | Hyperglycemia | Hyperhidrosis | Hyperkalemia | Hypermagnesemia | Hypernatremia | Hypertension | Hyperuricemia | Hypoalbuminemia | Hypocalcemia | Hypoglycemia | Hypokalemia | Hypomagnesemia | Hyponatremia | Hypophosphatemia | Hypotension | Hypoxia | Ileus | Infections and infestations - Other, specify | Infective myositis | Injury, poison and procedural complications-Other | Intracranial hemorrhage | Investigations - Other, specify | Irregular menstruation | Jejunal obstruction | Kidney infection | Laryngeal edema | Laryngeal mucositis | Left ventricular systolic dysfunction | Leukocytosis | Lipase increased | Lower gastrointestinal hemorrhage | Lung infection | Lymphocyte count decreased | Menorrhagia | Metabolism and nutrition disorders-Other, specify | Middle ear inflammation | Mucosal infection | Mucositis oral | Multi-organ failure | Musculoskeletal and connective tiss disorder-Other | Myalgia | Nausea | Neck edema | Nervous system disorders - Other, specify | Neutrophil count decreased | Non-cardiac chest pain | Oral pain | Pain | Pain in extremity | Palmar-plantar erythrodysesthesia syndrome | Papulopustular rash | Paresthesia | Pericardial effusion | Pericardial tamponade | Periorbital edema | Peripheral sensory neuropathy | Pharyngeal mucositis | Pharyngitis | Platelet count decreased | Pleural effusion | Pneumonitis | Pruritus | Pulmonary edema | Purpura | Rash acneiform | Rash maculo-papular | Rectal hemorrhage | Rectal pain | Renal and urinary disorders - Other, specify | Resp, thoracic and mediastinal disorders - Other | Respiratory failure | Restrictive cardiomyopathy | Salivary duct inflammation | Scrotal infection | Scrotal pain | Seizure | Sepsis | Sinus bradycardia | Sinus tachycardia | Sinusitis | Skin and subcutaneous tissue disorders - Other | Skin infection | Skin ulceration | Small intestinal obstruction | Soft tissue infection | Sore throat | Stomach pain | Stroke | Supraventricular tachycardia | Syncope | Testicular disorder | Thromboembolic event | Thrombotic thrombocytopenic purpura | Tooth infection | Tumor lysis syndrome | Typhlitis | Upper gastrointestinal hemorrhage | Upper respiratory infection | Urinary incontinence | Urinary tract infection | Urine output decreased | Vaginal hemorrhage | Vascular access complication | Vasovagal reaction | Ventricular tachycardia | Vomiting | Weight loss | White blood cell decreased | Wound infection |
|---|
| Arm I (Standard Dose Cytarabine, Daunorubicin Hydrochloride) | 1 | 1 | 4 | 1 | 2 | 1 | 12 | 2 | 1 | 0 | 0 | 0 | 0 | 158 | 0 | 5 | 8 | 0 | 0 | 0 | 0 | 1 | 9 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 3 | 1 | 0 | 0 | 3 | 2 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 15 | 2 | 0 | 0 | 1 | 1 | 1 | 3 | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 1 | 3 | 0 | 14 | 152 | 4 | 3 | 0 | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 1 | 1 | 2 | 3 | 0 | 0 | 1 | 1 | 1 | 5 | 1 | 0 | 0 | 0 | 7 | 0 | 5 | 8 | 0 | 18 | 0 | 20 | 21 | 3 | 2 | 0 | 18 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 0 | 21 | 89 | 1 | 1 | 1 | 1 | 19 | 1 | 0 | 0 | 7 | 0 | 0 | 141 | 1 | 5 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 175 | 1 | 1 | 0 | 1 | 0 | 1 | 11 | 1 | 1 | 0 | 1 | 3 | 1 | 1 | 0 | 0 | 1 | 16 | 0 | 0 | 2 | 0 | 5 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 2 | 0 | 1 | 3 | 1 | 4 | 8 | 1 | 2 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 156 | 1 |
,| Arm II (High-dose Cytarabine, Idarubicin) | 0 | 1 | 6 | 1 | 5 | 3 | 17 | 2 | 1 | 0 | 0 | 1 | 0 | 164 | 0 | 16 | 15 | 0 | 3 | 1 | 1 | 1 | 15 | 0 | 1 | 1 | 2 | 1 | 3 | 1 | 1 | 7 | 0 | 2 | 0 | 9 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 6 | 1 | 0 | 0 | 3 | 20 | 1 | 1 | 2 | 0 | 0 | 1 | 7 | 0 | 3 | 6 | 2 | 1 | 6 | 4 | 1 | 0 | 0 | 0 | 1 | 2 | 1 | 18 | 160 | 7 | 2 | 0 | 2 | 0 | 0 | 5 | 4 | 1 | 0 | 0 | 0 | 2 | 2 | 1 | 2 | 0 | 1 | 0 | 12 | 1 | 1 | 1 | 0 | 6 | 1 | 8 | 17 | 0 | 20 | 1 | 20 | 31 | 12 | 4 | 1 | 21 | 0 | 0 | 0 | 6 | 0 | 0 | 1 | 0 | 0 | 3 | 1 | 0 | 1 | 22 | 107 | 0 | 1 | 0 | 0 | 18 | 3 | 1 | 0 | 15 | 0 | 1 | 128 | 0 | 5 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 168 | 0 | 4 | 1 | 2 | 1 | 1 | 26 | 0 | 0 | 1 | 3 | 8 | 0 | 0 | 0 | 0 | 0 | 26 | 0 | 2 | 0 | 2 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 8 | 14 | 0 | 1 | 0 | 2 | 0 | 0 | 2 | 1 | 1 | 6 | 0 | 150 | 0 |
,| Arm III (Vorinostat, High-dose Cytarabine, Idarubicin) | 1 | 1 | 9 | 2 | 4 | 4 | 20 | 1 | 2 | 2 | 1 | 0 | 1 | 106 | 4 | 12 | 12 | 1 | 1 | 1 | 0 | 0 | 22 | 0 | 0 | 3 | 0 | 0 | 2 | 1 | 0 | 4 | 0 | 0 | 1 | 5 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 3 | 0 | 0 | 38 | 1 | 0 | 0 | 0 | 0 | 0 | 8 | 1 | 2 | 4 | 2 | 0 | 5 | 4 | 2 | 0 | 1 | 1 | 0 | 1 | 0 | 13 | 114 | 6 | 4 | 1 | 3 | 0 | 0 | 1 | 1 | 2 | 1 | 0 | 0 | 4 | 3 | 0 | 0 | 0 | 0 | 1 | 16 | 0 | 1 | 0 | 2 | 6 | 1 | 8 | 25 | 1 | 24 | 2 | 9 | 31 | 9 | 9 | 2 | 14 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 3 | 14 | 77 | 0 | 0 | 0 | 1 | 11 | 5 | 1 | 1 | 5 | 1 | 0 | 104 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 128 | 1 | 2 | 1 | 5 | 0 | 0 | 10 | 0 | 1 | 0 | 2 | 14 | 0 | 0 | 1 | 1 | 1 | 34 | 1 | 2 | 0 | 1 | 4 | 1 | 0 | 0 | 2 | 0 | 1 | 1 | 3 | 0 | 0 | 1 | 0 | 9 | 23 | 1 | 2 | 1 | 6 | 1 | 2 | 1 | 1 | 0 | 4 | 2 | 112 | 0 |
Complete Response Rate (Complete Response + Stringent Complete Response)
Defined by the International Myeloma Working Group (IMWG) criteria (NCT01653418)
Timeframe: Day +100
| Intervention | participants (Number) |
|---|
| V-BEAM + Stem Cell Infusion | 6 |
Time to Neutrophil Engraftment After V-BEAM.
Time to neutrophil engraftment is defined as duration between Day 0 to the first day of ANC > 0.5x109/L post transplant when it is sustained for more than three consecutive days. (NCT01653418)
Timeframe: Day +100
| Intervention | days (Median) |
|---|
| V-BEAM + Stem Cell Infusion | 10 |
Treatment Related Mortality (TRM) of V-BEAM
(NCT01653418)
Timeframe: Day +100
| Intervention | participants (Number) |
|---|
| V-BEAM + Stem Cell Infusion | 2 |
Very Good Partial Response Rate (VGPR+nCR+sCR+CR)
Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria. (NCT01653418)
Timeframe: Day +100
| Intervention | participants (Number) |
|---|
| V-BEAM + Stem Cell Infusion | 8 |
Number of Participants With Overall Survival (OS)
OS is defined as the duration from the time of transplant to death or last follow-up. (NCT01653418)
Timeframe: Median follow-up of 6 months (range: 6-12 months)
| Intervention | participants (Number) |
|---|
| Expired Day +3 | Expired Day +18 | Alive |
|---|
| V-BEAM + Stem Cell Infusion | 1 | 1 | 8 |
Number of Participants With Progression-free Survival (PFS)
"PFS is defined as the duration from transplant to time of first progression, death, relapse after CR, or the date the patient was last known to be in remission.~Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria." (NCT01653418)
Timeframe: Median follow-up of 6 months (range: 6.0-12.0 months)
| Intervention | participants (Number) |
|---|
| No relapse/progression | Relapse/progression at 12 months |
|---|
| V-BEAM + Stem Cell Infusion | 7 | 1 |
Overall Response Rate (ORR)
"ORR includes Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR)~Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria." (NCT01653418)
Timeframe: 3 months following Day +100 visit
| Intervention | participants (Number) |
|---|
| Partial response | Very good partial response | Complete response |
|---|
| V-BEAM + Stem Cell Infusion | 0 | 2 | 6 |
Time to Platelet Engraftment After V-BEAM.
Time to platelet engraftment is defined as the duration between Day 0 to the first day of platelet count sustained at > 20x109/L without transfusion. The median time to neutrophil and platelet engraftment will be reported. (NCT01653418)
Timeframe: Day +100
| Intervention | days (Median) |
|---|
| More than 20 x 10^9/L | More than 50 x 10^9/L |
|---|
| V-BEAM + Stem Cell Infusion | 22.5 | 23 |
Toxicity of V-BEAM
"Graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.~Patients are evaluated from first receiving study treatment until a 30-day follow-up after the conclusion of treatment for adverse events not resulting in death. Adverse events resulting in death will be evaluated through Day +100.~This outcomes measures the common toxicities observed. Please refer to the Serious Adverse Event and Other Adverse Event sections of the results for further details." (NCT01653418)
Timeframe: 30 days after end of treatment / Day +100
| Intervention | participants (Number) |
|---|
| Neutropenic fever | Clostridium difficile colitis | Neutropenic colitis without Clostridium difficile | Sepsis | Mucositis (grade 1-2) | Mucositis (grade 3-4) | Diarrhea (grade 3-4) | Hepatic toxicity (grade 3-4) | Peripheral neuropathy (grade 1-2) | Toxic death |
|---|
| V-BEAM + Stem Cell Infusion | 10 | 3 | 3 | 3 | 8 | 2 | 10 | 1 | 2 | 2 |
3-Year Overall Survival
Number of participants alive 3 years following treatment. Evaluations done every 3 months for 1 year and then every 6 months to check on the status of the disease. (NCT01538472)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| Y Zevalin + BEAM | 78 |
Overall Survival Median
Overall survival reported as number of days participants alive following treatment up to 5 years with annual follow up till disease progression. Evaluations done every 3 months for 1 year and then every 6 months for 5 years to check on the status of the disease, with long-term follow up as needed. (NCT01538472)
Timeframe: Participant followed from baseline treatment to 5 years, with study total period 8 years (study duration)
| Intervention | days (Median) |
|---|
| Y Zevalin + BEAM | 1299 |
Number of Participants With Minimal Residual Disease (MRD)-Negative Complete Remission (CR) at The End of Induction Phase
MRD-negative CR was achieved when a participant met the criteria for both MRD negativity and CR. MRD-negativity: ≤0.01 % breakpoint cluster region-Abelson (BCR-ABL1/ABL1), or undetectable BCR-ABL1 transcripts in complementary deoxyribonucleic acid (cDNA) with ≥ 10,000 ABL1 transcripts. CR: meeting all the following for at least 4 weeks (that is no recurrence):1. No circulating blasts and less than (<) 5% blasts in the bone marrow (BM). 2. Normal maturation of all cellular components in the BM. 3. No extramedullary disease (central nervous system [CNS] involvement, lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass). 4. Absolute neutrophil count (ANC) > 1000 per microliter (/mcL) (or >1.0*10^9/L). 5. Platelets >100,000/mcL (or >100*10^9/L). (NCT03589326)
Timeframe: From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length = 28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: Ponatinib 30 mg | 53 |
| Cohort B: Imatinib 600 mg | 13 |
Event Free Survival
Observed length of time (days) after which patients remained free of recurrence or death. (NCT02440568)
Timeframe: 6 months
| Intervention | Days (Median) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 66 |
| Patients With Newly Diagnosed AML, Cohort 2 | 90.5 |
| Patients With Newly Diagnosed AML, Cohort 3 | 65.5 |
| Patients With Newly Diagnosed AML, Cohort 4 | 33 |
Optimally Tolerated Dose
"The primary endpoint is determination of the optimally active and safe dose (OD) of Omacetaxine when added to the standard-of-care induction chemotherapy for AML and estimation of the efficacy and response rate.~OD will be defined as a dose level at which fewer than 30% of patients experience hematologic toxicity and greater than 50% of patients achieve a CR (50% is an accepted CR rate in AML when using a single induction)." (NCT02440568)
Timeframe: Within 50 days (duration of hematologic recovery)
| Intervention | Participants treated with OD (Number) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 0 |
| Patients With Newly Diagnosed AML, Cohort 2 | 0 |
| Patients With Newly Diagnosed AML, Cohort 3 | 10 |
| Patients With Newly Diagnosed AML, Cohort 4 | 0 |
Overall Participant Survival
Observed overall survival among participants (days) (NCT02440568)
Timeframe: 3 years
| Intervention | Days (Median) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 726 |
| Patients With Newly Diagnosed AML, Cohort 2 | 162.5 |
| Patients With Newly Diagnosed AML, Cohort 3 | 792.5 |
| Patients With Newly Diagnosed AML, Cohort 4 | 33 |
Progression Free Survival
Among the participants who achieved CR,CRi, progression free survival in number of days, i.e. the number of days participants who achieved CR/CRi remained alive and in a remission. (NCT02440568)
Timeframe: 3 years
| Intervention | Days (Median) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 852.5 |
| Patients With Newly Diagnosed AML, Cohort 2 | 100 |
| Patients With Newly Diagnosed AML, Cohort 3 | 1241.5 |
| Patients With Newly Diagnosed AML, Cohort 4 | 1141 |
Time to Hematologic Recovery
Time to Absolute Neutrophil Count > 1.0 x 10e9/L and Platelet Count > 100 x 10e9/L, whichever was later, for those patients who achieved a remission and achieved these hematologic goals. (NCT02440568)
Timeframe: Within 6 months of last dose of Omacetaxine
| Intervention | Days (Median) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 25.5 |
| Patients With Newly Diagnosed AML, Cohort 2 | 35 |
| Patients With Newly Diagnosed AML, Cohort 3 | 33.5 |
| Patients With Newly Diagnosed AML, Cohort 4 | 36 |
Toxicity: Describe by the Adverse Events as Assessed by the CTCAE Grading
Describe the adverse events associated with Omacetaxine when administered in combination with cytarabine and Idarubicin as induction therapy for AML, using CTCAE grading (NCT02440568)
Timeframe: Up to 6 months after last dose of Omacetaxine
| Intervention | Total Adverse Events (Number) |
|---|
| Patients With Newly Diagnosed AML, Cohort 1 | 47 |
| Patients With Newly Diagnosed AML, Cohort 2 | 88 |
| Patients With Newly Diagnosed AML, Cohort 3 | 219 |
| Patients With Newly Diagnosed AML, Cohort 4 | 37 |
Engraftment of HLA Identical PBSC Allografts
"Number of patients who engrafted by Day 56 post allogeneic transplant. Failure to engraft is defined as the absence of detectable donor cells in the marrow. The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess failure rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease)." (NCT00005803)
Timeframe: Day 56
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Tandem Transplantation) | 53 |
Non-Relapse Mortality
"The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess failure rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease)." (NCT00005803)
Timeframe: Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Tandem Transplantation) | 3 |
Overall Survival (OS)
Number of patients surviving by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. (NCT00005803)
Timeframe: From the date of autologous transplant until the time of death, assessed up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| 6 Months | 1 Year | 1.5 Years | 2 Years | 3 Years |
|---|
| Chemoresistant Group | 14 | 10 | 9 | 8 | 8 |
,| Chemosensitive Group | 39 | 31 | 27 | 26 | 23 |
,| Unknown Chemosensitivity Group | 1 | 0 | 0 | 0 | 0 |
Progression Free-survival (PFS)
Number of patients surviving without disease by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. (NCT00005803)
Timeframe: From the date of autologous transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, assessed up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| 6 Months | 1 Year | 1.5 Years | 2 Years | 3 Years |
|---|
| Chemoresistant Group | 12 | 8 | 8 | 8 | 8 |
,| Chemosensitive Group | 36 | 27 | 25 | 25 | 22 |
,| Unknown Chemosensitivity Group | 1 | 0 | 0 | 0 | 0 |
Clinical Benefit as Measured by the Number of Patients Who Were Not RBC Transfusion-dependent Post-Baseline
Clinical benefit as measured by the number of patients who did not receive a RBC transfusion post-Baseline (NCT02666950)
Timeframe: Up to 17 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) | 0 |
Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels
Complete response rate will be evaluated over all courses of study treatment. The proportion of CR/CRi responses will be estimated by the number of CR/CRi responses divided by the total number of evaluable patients. (NCT02666950)
Timeframe: Up to 17 months
| Intervention | percentage of patients (Number) |
|---|
| Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) | 0 |
Overall Survival
Overall survival time is defined as the time from registration to death due to any cause. (NCT02666950)
Timeframe: From registration to death due to any cause, assessed up to 17 months
| Intervention | months (Median) |
|---|
| Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) | 6 |
Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment
"The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either unrelated or unlikely to be related to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below." (NCT02666950)
Timeframe: Up to 30 days post-treatment
| Intervention | percentage of patients (Number) |
|---|
| Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) | 100 |
Time to Progression, Defined as the Time From Registration to the Earliest Date of Documentation of Disease Progression
Time to progression (TTP) is defined to be the length of time from study registration to a) date of disease progression as defined by section 11.0 of the protocol, or b) last follow-up. If a patient dies without documentation of disease progression, the patient will be considered to have had a tumor progression at the time of death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Time to progression curves were compared via the log-rank test. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan. (NCT02666950)
Timeframe: Up to 17 months
| Intervention | months (Median) |
|---|
| Arm A + Arm C (AZD1775 Combined With AraC OR AZD1775 Only) | 3.9 |
Disease Free Survival
1 year disease free survival rate following adoptive transfer (NCT02046122)
Timeframe: one year following adoptive transfer
| Intervention | Participants (Count of Participants) |
|---|
| Idarubicin + Cytarabine + DLI | 3 |
Number of Participants With Immune Recovery
Immune recovery determined by measurements of cytokine profiles, lymphocyte and natural killer (NK) enumeration and flow-based assays, measured prior to induction, prior to each round of consolidation, 8 weeks after the last cycle of consolidation, and every 3 months after treatment for up to 2 years (NCT02046122)
Timeframe: up to 2 years after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Idarubicin + Cytarabine + DLI | 3 |
Number of Subjects With Unacceptable Toxicity
"Unacceptable toxicity is defined as:~i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days;~ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days~iii. Treatment-related mortality (TRM)" (NCT02046122)
Timeframe: up to 8 weeks after last cell infusion
| Intervention | Participants (Count of Participants) |
|---|
| Idarubicin + Cytarabine + DLI | 1 |
Overall Survival
Number of participants alive 2 years after completing adoptive transfer therapy. (NCT02046122)
Timeframe: 2 years after completing therapy
| Intervention | participants (Number) |
|---|
| Idarubicin + Cytarabine + DLI | 16 |
Percentage of Subjects With Acute GVHD
Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days (NCT02046122)
Timeframe: 8 weeks after last cell infusion
| Intervention | percentage of participants (Number) |
|---|
| Idarubicin + Cytarabine + DLI | 0 |
Percentage of Subjects With Unacceptable Toxicity
Grade IV CTCAE toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days, Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days, or death (NCT02046122)
Timeframe: 8 weeks after the last cell infusion
| Intervention | percentage of participants (Number) |
|---|
| Idarubicin + Cytarabine + DLI | 5.88 |
Rate of Efficacy
Efficacy as measured by the number of subjects with a complete remission. Responses were evaluated according to standard criteria defined by the National Comprehensive Cancer Network Guidelines for AML (www.nccn.org). (NCT02046122)
Timeframe: 2 years after completing therapy
| Intervention | Participants (Count of Participants) |
|---|
| Idarubicin + Cytarabine + DLI | 10 |
Number of Days to Hematopoietic Recovery
Hematopoietic recovery as measured by the date of the first of three consecutive laboratory values where the absolute neutrophil count (ANC) ≥ 500/μl , the date of the first of three consecutive laboratory values obtained on different days where the platelet count was > 20,000/μl without transfusion. (NCT02046122)
Timeframe: 2 years after completion of therapy
| Intervention | days (Median) |
|---|
| Neutrophil recovery | Platelet recovery |
|---|
| Idarubicin + Cytarabine + DLI | 29 | 32 |
Frequency of Adverse Events, Graded According to NCI CTCAE v4.0
Maximum grade per participant of any AE. (NCT02029417)
Timeframe: Up to 30 days after last dose of study drugs
| Intervention | participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Treatment (Cytarabine, Omacetaxine Mepesuccinate, Decitabine) | 0 | 0 | 0 | 2 |
Multiple Dose- Accumulation Ratio (Rac) of PF-04449913: Monotherapy Cohort
Rac was the observed accumulation ratio for AUCtau, determined as ratio of Day 21 AUCtau to Day -5 AUCtau. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 and Day 21 of Cycle 1
| Intervention | Ratio (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 1.893 |
| Monotherapy Cohort: PF-04449913 50 mg | 2.076 |
| Monotherapy Cohort: PF-04449913 100 mg | 1.752 |
Multiple Dose- AUCtau of Daunorubicinol: Combination Cohort 2
Daunorubicinol was a metabolite of daunorubicin. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 2800 |
Multiple Dose- AUCtau of PF-04449913: Monotherapy Cohort
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 4561 |
| Monotherapy Cohort: PF-04449913 50 mg | 9299 |
| Monotherapy Cohort: PF-04449913 100 mg | 15480 |
Multiple Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1
| Intervention | Liter per hour (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 5.467 |
| Monotherapy Cohort: PF-04449913 50 mg | 5.369 |
| Monotherapy Cohort: PF-04449913 100 mg | 6.452 |
Multiple Dose- Steady State Accumulation Ratio (Rss) of PF-04449913: Monotherapy Cohort
Rss = Ratio of Day 21 AUCtau to Day -5 AUCinf. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Ratio (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 1.355 |
| Monotherapy Cohort: PF-04449913 50 mg | 1.017 |
| Monotherapy Cohort: PF-04449913 100 mg | 1.176 |
Multiple Dose- T1/2 of Daunorubicin: Combination Cohort 2
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium (NCT02038777)
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of at induction Cycle 1
| Intervention | Hours (Mean) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 7.297 |
Multiple Dose- Tmax of Daunorubicin: Combination Cohort 2
(NCT02038777)
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1
| Intervention | Hours (Median) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 0.3585 |
Multiple Dose- Tmax of Daunorubicinol: Combination Cohort 2
Daunorubicinol was a metabolite of daunorubicin. (NCT02038777)
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1
| Intervention | Hours (Median) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 0.3585 |
Multiple Dose- Tmax of PF-04449913: Monotherapy Cohort
(NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 3.970 |
| Monotherapy Cohort: PF-04449913 50 mg | 4.000 |
| Monotherapy Cohort: PF-04449913 100 mg | 1.950 |
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 1
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. (NCT02038777)
Timeframe: Baseline up to maximum 486 days
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 0 |
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 2
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. (NCT02038777)
Timeframe: Baseline up to maximum 343 days
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 0 |
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 3
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. (NCT02038777)
Timeframe: Baseline up to maximum 841 days
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 0 |
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Monotherapy Cohort
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion. (NCT02038777)
Timeframe: For 25 mg: Baseline up to maximum 108 days; For 50 mg: Baseline up to maximum 151 days; For 100 mg: Baseline up to maximum 444 days
| Intervention | Participants (Count of Participants) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 0 |
| Monotherapy Cohort: PF-04449913 50 mg | 0 |
| Monotherapy Cohort: PF-04449913 100 mg | 0 |
Number of Participants With DLTs: Combination Cohort 1
Criteria: Grade >=3 non-hematologic toxicity (nht), except Grade >=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade <=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted >42 days from point of detection = absolute neutrophil count < 500/microliter or platelet count <10*10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); Inability to deliver >=80% of the planned study doses for all agents in a combination due to nht; Delay of >28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade >=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT. (NCT02038777)
Timeframe: Day 1 up to Day 28 of Cycle 1 (28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 0 |
Number of Participants With DLTs: Combination Cohort 2
Criteria: Grade >=3 non-hematologic toxicity (nht), except Grade >=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade <=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted >42 days from point of detection = absolute neutrophil count < 500/microliter or platelet count <10*10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); Inability to deliver >=80% of the planned study doses for all agents in a combination due to nht; Delay of >28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade >=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT. (NCT02038777)
Timeframe: Day -3 up to anytime between Day 21 and Day 28 of first induction cycle (24 to 31 days)
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 1 |
Number of Participants With DLTs: Combination Cohort 3
Criteria: Grade >=3 non-hematologic toxicity (nht), except Grade >=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade <=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted >42 days from point of detection = absolute neutrophil count < 500/microliter or platelet count <10*10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); Inability to deliver >=80% of the planned study doses for all agents in a combination due to nht; Delay of >28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade >=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT. (NCT02038777)
Timeframe: Day 1 up to Day 28 of Cycle 1 (28 days)
| Intervention | Participants (Count of Participants) |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 0 |
Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy Cohort
Criteria: Grade >=3 non-hematologic toxicity (nht), except Grade >=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade <=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted >42 days from point of detection = absolute neutrophil count < 500/microliter or platelet count <10*10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); Inability to deliver >=80% of the planned study doses for all agents in a combination due to nht; Delay of >28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade >=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT. (NCT02038777)
Timeframe: Day -5 up to Day 28 of Cycle 1 (33 days)
| Intervention | Participants (Count of Participants) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 0 |
| Monotherapy Cohort: PF-04449913 50 mg | 0 |
| Monotherapy Cohort: PF-04449913 100 mg | 0 |
Overall Survival: Combination Cohort 1
Overall survival was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. (NCT02038777)
Timeframe: First dose of study drug up to death or date of last contact (maximum up to 514 days)
| Intervention | Months (Median) |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 11.8 |
Percentage of Participants Achieving Disease Modifying Response (DMR): Expansion Cohort
DMR included complete remission (CR), CR with incomplete blood count recovery (Cri), morphologic leukemia-free state (MLFS), marrow CR (mCR) and partial remission (PR). CR: >=11 gram per deciliter (g/dL) hemoglobin (Hgb), >=1*10^9 neutrophils (L), >=100*10^9 platelets (L), 0% blasts, <=5% bone marrow blasts (BMB), normal maturation of all cell lines, if had persistent dysplasia. . CRi: <1000 neutrophils (mcL), <100000 platelets (mcL), <5% BMB, either neutrophils or platelets not recovered, no extramedullary disease (EMD). MLFS: 1000 neutrophils (mcL) and <100000 platelets (mcL), <5% BMB, neutrophils and platelets not recovered, flow cytometry negative, no EMD. PR: >=1000 neutrophils (mcL), >=100000 platelets (mcL), decrease to 5-25 and >=50% decrease from start, Blasts <=5% if Auer rod positive. mCR: hematologic improvement (HI) response, <=5% and decreased by >=50% BMB. PR: decrease by >=50% but still >5% BMB. (NCT02038777)
Timeframe: Baseline up to maximum 736 days
| Intervention | Percentage of participants (Number) |
|---|
| Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg | 46.7 |
Single Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Liter per hour (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 7.415 |
| Monotherapy Cohort: PF-04449913 50 mg | 5.210 |
| Monotherapy Cohort: PF-04449913 100 mg | 7.599 |
Single Dose- Maximum Observed Plasma Concentration (Cmax) of PF-04449913: Monotherapy Cohort
(NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | nanogram per milliliter (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 281.5 |
| Monotherapy Cohort: PF-04449913 50 mg | 321.1 |
| Monotherapy Cohort: PF-04449913 100 mg | 1019 |
Single Dose- Terminal Plasma Half-life (T1/2) of PF-04449913: Monotherapy Cohort
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Hours (Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 17.83 |
| Monotherapy Cohort: PF-04449913 50 mg | 30.70 |
| Monotherapy Cohort: PF-04449913 100 mg | 18.67 |
Single Dose- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04449913: Monotherapy Cohort
(NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 1.970 |
| Monotherapy Cohort: PF-04449913 50 mg | 3.955 |
| Monotherapy Cohort: PF-04449913 100 mg | 1.950 |
Single Dose- Volume of Distribution (Vz/F) of PF-04449913: Monotherapy Cohort
Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Liter (Geometric Mean) |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 190.5 |
| Monotherapy Cohort: PF-04449913 50 mg | 227.8 |
| Monotherapy Cohort: PF-04449913 100 mg | 201.5 |
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 1
Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for patients who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)
| Intervention | Months (Median) |
|---|
| Duration of CR/CRi | Duration of DMR |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 13.9 | 15.3 |
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for patients who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)
| Intervention | Months (Median) |
|---|
| Duration of CR/CRi | Duration of DMR |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 6.6 | 6.6 |
Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1; Cavg: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; Ctrough: Pre-dose on Day 21 of Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax | Cmin | Cavg | Ctrough |
|---|
| Monotherapy Cohort: PF-04449913 100 mg | 1330 | 333.9 | 645.8 | 342.9 |
,| Monotherapy Cohort: PF-04449913 25 mg | 356.9 | 84.94 | 190.5 | 87.87 |
,| Monotherapy Cohort: PF-04449913 50 mg | 542.2 | 237.2 | 388.1 | 240.0 |
Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1
LDAC= low dose ara-cytarabine/low dose cytarabine. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 12 hours. (NCT02038777)
Timeframe: AUCinf: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; AUCtau: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| AUCinf: Cycle 1/Day 2 | AUCtau: Cycle 1/Day 2 | AUCinf: Cycle 1/Day 10 | AUCtau: Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 78.37 | 77.97 | 97.34 | 97.58 |
Multiple Dose- AUCinf and AUCtau of Daunorubicin: Combination Cohort 2
AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: AUCinf: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1; AUCtau: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| AUCinf | AUCtau |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 770.4 | 741.6 |
Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. (NCT02038777)
Timeframe: AUCinf: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at 7 of Cycle 1; AUCtau: 0 to 24 hours post azacitidine dosing on Day 1 and 7 of Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| AUCtau: Cycle 1/Day 1 | AUCinf: Cycle 1/Day 1 | AUCtau: Cycle 1/Day 7 | AUCinf: Cycle 1/Day 7 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 1200 | 910.9 | 1241 | 1200 |
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 1
AUCtau was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: 0 to 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 15560 | 16070 |
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 2
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| Cycle 1/Day 3 | Cycle 1/Day 10 |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 15630 | 18120 |
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 3
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. (NCT02038777)
Timeframe: 0 to 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| Cycle 1/Day 7 | Cycle 1/Day 21 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 20010 | 16860 |
Multiple Dose- CL/F of PF-04449913: Combination Cohort 1
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1
| Intervention | Liter per hour (Geometric Mean) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 6.428 | 6.223 |
Multiple Dose- CL/F of PF-04449913: Combination Cohort 2
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT02038777)
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1
| Intervention | Liter per hour (Geometric Mean) |
|---|
| Cycle 1/Day 3 | Cycle 1/Day 10 |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 6.401 | 5.523 |
Multiple Dose- CL/F of PF-04449913: Combination Cohort 3
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT02038777)
Timeframe: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1
| Intervention | Liter per hour (Geometric Mean) |
|---|
| Cycle 1/Day 7 | Cycle 1/Day 21 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 4.999 | 5.936 |
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Ara-uridine was a metabolite of cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data. Ara-uridine was a metabolite of cytarabine. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dosing on Day 2 and Day 10 of Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 2 | Cmin: Cycle 1/Day 2 | Ctrough: Cycle 1/Day 2 | Cmax: Cycle 1/Day 10 | Cmin: Cycle 1/Day 10 | Ctrough: Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 371.6 | 141.9 | 141.9 | 454.3 | 201.7 | 201.7 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax: 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 1/Cycle 1;Cmin: Pre-dose, 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 7/Cycle 1;Cavg: 0 to 24 hrs post azacitidine dose on Day 7/Cycle 1;Ctrough:Pre azacitidine dose on Day 7/Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 1 | Cmax: Cycle 1/Day 7 | Cmin: Cycle 1/Day 7 | Cavg: Cycle 1/Day 7 | Ctrough: Cycle 1/Day 7 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 1803 | 1717 | NA | 51.60 | NA |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
LDAC= low dose ara-cytarabine/low dose cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dose on Day 2 and Day 10 of Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 2 | Cmin: Cycle 1/Day 2 | Cavg: Cycle 1/Day 2 | Ctrough: Cycle 1/Day 2 | Cmax: Cycle 1/Day 10 | Cmin: Cycle 1/Day 10 | Cavg: Cycle 1/Day 10 | Ctrough: Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 82.88 | NA | 6.511 | NA | 106.7 | 0.5903 | 8.135 | 0.5903 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax | Cmin | Cavg | Ctrough |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 942.8 | 2.589 | 30.89 | 2.673 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. Daunorubicinol was a metabolite of daunorubicin. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax | Cmin | Cavg | Ctrough |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 244.4 | 66.38 | 116.7 | 66.53 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle 1; Cavg: 0 to 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle; Ctrough: Pre-dose on Day 10 and 21 of Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 10 | Cmin: Cycle 1/Day 10 | Cavg: Cycle 1/Day 10 | Ctrough: Cycle 1/Day 10 | Cmax: Cycle 1/Day 21 | Cmin: Cycle 1/Day 21 | Cavg: Cycle 1/Day 21 | Ctrough: Cycle 1/Day 21 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 1172 | 317.6 | 648.3 | 330.7 | 1317 | 341.6 | 670.5 | 376.2 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose, 0.5, 1, 6, and 24 hrs post dose on Day 3, 10 of induction Cycle (IC) 1 and 4 hrs post dose on Day 10 of IC 1; Cavg: 0 to 24 hrs post dose on Day 3 and Day 10 of IC 1; Ctrough: Pre dose on Day 3 and Day 10 of IC 1 (PF-04449913 Dose)
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 3 | Cmin: Cycle 1/Day 3 | Cavg: Cycle 1/Day 3 | Ctrough: Cycle 1/Day 3 | Cmax: Cycle 1/Day 10 | Cmin: Cycle 1/Day 10 | Cavg: Cycle 1/Day 10 | Ctrough: Cycle 1/Day 10 |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 1047 | 318.2 | 650.9 | 354.0 | 1181 | 356.1 | 755.2 | 359.5 |
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. (NCT02038777)
Timeframe: Cmax, Cmin: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Cavg: 0 to 24 hors post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Ctrough: Pre PF-04449913 dosing on Day 7 and Day 21 of Cycle 1
| Intervention | Nanogram per milliliter (Geometric Mean) |
|---|
| Cmax: Cycle 1/Day 7 | Cmin: Cycle 1/Day 7 | Cavg: Cycle 1/Day 7 | Ctrough: Cycle 1/Day 7 | Cmax: Cycle 1/Day 21 | Cmin: Cycle 1/Day 21 | Cavg: Cycle 1/Day 21 | Ctrough: Cycle 1/Day 21 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 1387 | 414.1 | 834.6 | 526.3 | 1218 | 323.2 | 701.9 | 347.5 |
Multiple Dose- T1/2 of Cytarabine: Combination Cohort 1
LDAC= low dose ara-cytarabine/low dose cytarabine. Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium. (NCT02038777)
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1
| Intervention | Hours (Mean) |
|---|
| Cycle 1/Day 2 | Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 1.027 | 0.8618 |
Multiple Dose- Tmax of Ara-uridine: Combination Cohort 1
Ara-uridine was a metabolite of cytarabine. (NCT02038777)
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 2 | Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 1.515 | 2.000 |
Multiple Dose- Tmax of Azacitidine: Combination Cohort 3
(NCT02038777)
Timeframe: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 7 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Day 1 | Day 7 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 0.2500 | 0.2500 |
Multiple Dose- Tmax of Cytarabine: Combination Cohort 1
LDAC= low dose ara-cytarabine/low dose cytarabine. (NCT02038777)
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 2 | Cycle 1/Day 10 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 0.2500 | 0.2500 |
Multiple Dose- Tmax of PF-04449913: Combination Cohort 1
(NCT02038777)
Timeframe: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 10 | Cycle 1/Day 21 |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 3.950 | 1.935 |
Multiple Dose- Tmax of PF-04449913: Combination Cohort 2
(NCT02038777)
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of Induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of Induction Cycle 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 3 | Cycle 1/Day 10 |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 5.950 | 5.065 |
Multiple Dose- Tmax of PF-04449913: Combination Cohort 3
(NCT02038777)
Timeframe: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1
| Intervention | Hours (Median) |
|---|
| Cycle 1/Day 7 | Cycle 1/Day 21 |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 4.000 | 2.500 |
Number of Participants With Best Response: Combination Cohort 1
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils [mcL] >=1000, platelets(pt)[mcL] >=10^5, BMB <5%. CRi: neutrophils (mcL) <1000 or pt (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and pt (mcL) <10^5, BMB <5%. PR: neutrophils (mcL) >=1000, pt (mcL) >=100000, decrease to 5-25 and >=50% decrease from start. PRi: neutrophils (mcL) <1000 or pt (mcL) <10^5, BMB decrease to 5-25 and >=50% decrease from start. Minor Response: BMB >=25% decrease from start. CRc: neutrophils (mcL) >1,000, pt (mcL) >10^6, BMB <5%. CRm: neutrophils (mcL) >1,000, pt (mcL) >100,000, BMB <5%. For participants with myelodysplastic syndrome (MDS), DMR- CR: >=11 Hgb (g/dL), >=1*10^9 neutrophils(L), >=100*10^9 pt(L), 0% blasts, <=5% BMB. mCR: HI response, <=5% and decreased by >=50% BMB. PR: decrease by >=50% but still >5% BMB. Only those responses which had at least 1 participant were reported. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)
| Intervention | Participants (Count of Participants) |
|---|
| Morphologic CR: AML | Stable disease: AML | Treatment failure: AML | Stable disease: MDS |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 1 | 1 | 2 | 2 |
Number of Participants With Best Response: Combination Cohort 2
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for AML- CR:neutrophils(nt)[mcL] >=1000, platelets (mcL) >=100000, BMB <5%. CRi: nt(mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: nt(mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: nt(mcL) >=1000, platelets (mcL) >=100000, decrease to 5-25 and >=50% decrease from start. PRi: nt(mcL) <1000 or platelets (mcL) <100000, BMB decrease to 5-25 and >=50% decrease from start. Minor Response: BMB >=25% decrease from start. Cytogenetic CR (CRc): nt(mcL) >1,000, platelets (mcL) >100,000, BMB <5%. CRm: nt(mcL) >1,000, platelets (mcL) >100,000, BMB <5%. For participants with myelodysplastic syndrome (MDS), DMR was defined as - CR: >=11 Hgb (g/dL), >=1*10^9 nt(L), >=100*10^9 platelets (L), 0% blasts, <=5% BMB. mCR: HI response, <=5% and decreased by >=50% BMB. PR: decrease by >=50% but still >5% BMB. Only those responses which had at least 1 participant were reported. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 343 days)
| Intervention | Participants (Count of Participants) |
|---|
| Morphologic CR: AML | Morphologic CRi: AML | MLFs: AML | PR: AML | MR: AML | Treatment failure: AML | Relapse: AML | Indeterminate: AML |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 3 | 2 | 2 | 1 | 2 | 1 | 1 | 1 |
Number of Participants With Best Response: Combination Cohort 3
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, decrease to 5-25 and >=50% decrease from start. PRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB decrease to 5-25 and >=50% decrease from start. Minor Response: BMB >=25% decrease from start. CRc: neutrophils (mcL) >1,000, platelets (mcL) >100,000, BMB <5%. CRm: neutrophils (mcL) >1,000, platelets (mcL) >100,000, BMB <5%. Only those responses which had at least 1 participant were reported. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)
| Intervention | Participants (Count of Participants) |
|---|
| Morphologic CR | PRi | Treatment failure |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 3 | 1 | 2 |
Number of Participants With Best Response: Monotherapy Cohort
Best response observed for: CR, Cri, MLFS, PR, PRi, CytogeneticCR(CRc), MolecularCR(CRm). For AML-CR:neutrophils(nt) [mcL]>=1000, platelets(pt)[mcL]>=10^5, BMB<5%. CRi:nt(mcL)<1000/pt(mcL)<10^5, BMB<5%. MLFS:nt(mcL)1000 and pt(mcL)<10^5, BMB<5%. PR:nt(mcL)>=1000, pt(mcL)>=10^5, decrease to 5-25 and >=50% decrease from start. PRi: nt<1000, <10^5. CRc: nt(mcL)>1,000, pt(mcL)>10^5, BMB<5%. CRm: nt(mcL)>1,000, pt(uL)>10^5, BMB<5%. For myelodysplasia-CR: hemoglobin(Hgb)[gram per deciliter{g/dL}]>=11, nt(L)>=1*10^9, pt(L)>=100*10^9, blasts0%, BMB<=5%. mCR:<=5% and decreased by >=50% BMB. PR:decrease by>=50% with >5% BMB, CRc: disappearance of chromosomal abnormality, no new appearance, PRc:>=50% reduced chromosomal abnormality. For myleofibrosis-CR: hgb(g/L)>=110, nt(L)>=1*10^9, pt(L)>=100*10^9, All <=ULN, BMB <=5%. PR: hgb>=110, nt(L)>=1*10^9, pt(L)>=100*10^9. CML- PR: 1-35% Philadelphia chromosome(PC) positive(+) cells, CR:0% PC+ cells. Responses with at least 1 participant were reported. (NCT02038777)
Timeframe: Day 1 up to End of Treatment (25 mg: maximum up to 108 days; 50 mg: maximum up to 151 days; 100 mg: maximum up to 444 days)
| Intervention | Participants (Count of Participants) |
|---|
| Morphologic CR: AML | Morphologic CRi: AML | MLFs: AML | Stable disease: AML | Treatment failure: AML | Marrow complete remission: MDS | Stable disease: MDS | Disease progression: MDS | Treatment failure: MDS | Stable disease: CML | Disease progression: CML |
|---|
| Monotherapy Cohort: PF-04449913 100 mg | 1 | 1 | 1 | 2 | 3 | 1 | 1 | 0 | 0 | 0 | 0 |
,| Monotherapy Cohort: PF-04449913 25 mg | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
,| Monotherapy Cohort: PF-04449913 50 mg | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 |
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated. (NCT02038777)
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 514 days)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs | Treatment Related TEAEs | Grade 3 or 4 TEAEs |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 6 | 1 | 6 | 4 |
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated. (NCT02038777)
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 371 days)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs | Treatment Related TEAEs | Grade 3 or 4 TEAEs |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 6 | 4 | 6 | 4 |
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated. (NCT02038777)
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 869 days)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs | Treatment related TEAEs | Grade 3 or 4 TEAEs |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 6 | 1 | 6 | 5 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE:any untoward medical occurrence at any dose that resulted in death;was life threatening;required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability/incapacity;resulted in congenital anomaly/birth defect. TEAEs:events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE:any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. National cancer institute common terminology criteria (NCI-CTCAE) Grade(G) v4.0:G 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G 4:life-threatening consequence, urgent intervention indicated. (NCT02038777)
Timeframe: Day 1 up to 28 days after last dose of study drug (For 25 mg: maximum up to 136 days; For 50 mg: maximum up to 179 days; For 100 mg: maximum up to 472 days)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs | Treatment related TEAEs | Grade 3 or 4 TEAEs |
|---|
| Monotherapy Cohort: PF-04449913 100 mg | 6 | 1 | 5 | 3 |
,| Monotherapy Cohort: PF-04449913 25 mg | 3 | 1 | 1 | 2 |
,| Monotherapy Cohort: PF-04449913 50 mg | 4 | 3 | 3 | 1 |
Percentage of Participants With Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR: Combination Cohort 1
CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)
| Intervention | Percentage of participants (Number) |
|---|
| CR/CRi | DMR |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 16.7 | 16.7 |
Percentage of Participants With CR/CRi and DMR: Combination Cohort 3
CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)
| Intervention | Percentage of participants (Number) |
|---|
| CR/Cri | DMR |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 50.0 | 50.0 |
Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. (NCT02038777)
Timeframe: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 of Cycle 1; AUClast and AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1
| Intervention | Nanogram*hour per milliliter (Geometric Mean) |
|---|
| AUCtau | AUClast | AUCinf |
|---|
| Monotherapy Cohort: PF-04449913 100 mg | 8843 | 12750 | 13160 |
,| Monotherapy Cohort: PF-04449913 25 mg | 2413 | 3255 | 3374 |
,| Monotherapy Cohort: PF-04449913 50 mg | 4499 | 8911 | 9596 |
Time to Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, bone marrow blasts (BMB) <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)
| Intervention | Months (Median) |
|---|
| Time to CR/CRi | Time to DMR |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 5.9 | 5.8 |
Time to Response: Combination Cohort 1
The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB <5%. CRi: neutrophils (mcL) <1000 or platelets (mcL) <100000, BMB <5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) <100000, BMB <5%. PR: neutrophils (mcL) >=1000, platelets (mcL) >=100000, BMB decrease to 5-25 and >=50% decrease from start. (NCT02038777)
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)
| Intervention | Months (Median) |
|---|
| Time to CR/CRi | Time to DMR |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 2.1 | 0.8 |
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'. (NCT02038777)
Timeframe: Baseline up to maximum 514 days
| Intervention | Participants (Count of Participants) |
|---|
| Lymphocytes/Leukocytes71912645 | Neutrophils/Leukocytes71912645 | Basophils/Leukocytes71912645 | Eosinophils/Leukocytes71912645 | Monocytes/Leukocytes71912645 | Prothrombin time71912645 | Blasts/Leukocytes71912645 | Lactate dehydrogenase71912645 | Protein71912645 | BUN71912645 | Urate71912645 | Chloride71912645 | Calcium71912645 | Urine specific gravity71912645 | Urine pH71912645 | Urine glucose71912645 | Urine ketones71912645 | Urine nitrite71912645 | Urine leukocyte esterase71912645 | Urine erythrocytes71912645 | Urine leukocytes71912645 |
|---|
| Normal | Abnormal low only | Abnormal high only | Abnormal low and abnormal high |
|---|
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 1 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 0 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 4 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 2 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 3 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 5 |
| Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg | 6 |
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'. (NCT02038777)
Timeframe: Baseline up to maximum 371 days
| Intervention | Participants (Count of Participants) |
|---|
| Lymphocytes/Leukocytes71912646 | Neutrophils/Leukocytes71912646 | Basophils/Leukocytes71912646 | Eosinophils/Leukocytes71912646 | Monocytes/Leukocytes71912646 | Prothrombin time71912646 | Blasts/Leukocytes71912646 | Lactate dehydrogenase71912646 | Protein71912646 | BUN71912646 | Urate71912646 | Chloride71912646 | Calcium71912646 | Urine specific gravity71912646 | Urine pH71912646 | Urine glucose71912646 | Urine ketones71912646 | Urine erythrocytes71912646 | Urine leukocytes71912646 |
|---|
| Abnormal low only | Abnormal low and abnormal high | Normal | Abnormal high only |
|---|
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 4 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 6 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 3 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 2 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 5 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 0 |
| Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin | 1 |
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'. (NCT02038777)
Timeframe: Baseline up to maximum 869 days
| Intervention | Participants (Count of Participants) |
|---|
| Lymphocytes/Leukocytes71912648 | Neutrophils/Leukocytes71912648 | Basophils/Leukocytes71912648 | Eosinophils/Leukocytes71912648 | Monocytes/Leukocytes71912648 | Blasts/Leukocytes71912648 | Lactate dehydrogenase71912648 | Protein71912648 | BUN71912648 | Urate71912648 | Chloride71912648 | Calcium71912648 | Urine specific gravity71912648 | Urine pH71912648 | Urine glucose71912648 | Urine ketones71912648 | Urine nitrite71912648 | Urine leukocyte esterase71912648 | Urine erythrocytes71912648 | Urine leukocytes71912648 |
|---|
| Abnormal low only | Abnormal high only | Abnormal low and abnormal high | Normal |
|---|
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 4 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 3 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 6 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 5 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 1 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 0 |
| Combination Cohort 3: PF-04449913 100 mg + Azacitidine | 2 |
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), blood urea nitrogen (BUN) (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'. (NCT02038777)
Timeframe: For 25 mg: Baseline up to maximum 136 days; For 50 mg: Baseline up to maximum 179 days; For 100 mg: Baseline up to maximum 472 days
| Intervention | Participants (Count of Participants) |
|---|
| Lymphocytes/Leukocytes71912642 | Lymphocytes/Leukocytes71912643 | Lymphocytes/Leukocytes71912644 | Neutrophils/Leukocytes71912642 | Neutrophils/Leukocytes71912643 | Neutrophils/Leukocytes71912644 | Basophils/Leukocytes71912642 | Basophils/Leukocytes71912643 | Basophils/Leukocytes71912644 | Eosinophils/Leukocytes71912643 | Eosinophils/Leukocytes71912644 | Eosinophils/Leukocytes71912642 | Monocytes/Leukocytes71912643 | Monocytes/Leukocytes71912644 | Monocytes/Leukocytes71912642 | Prothrombin time71912643 | Prothrombin time71912642 | Prothrombin time71912644 | Blasts/Leukocytes71912642 | Blasts/Leukocytes71912643 | Blasts/Leukocytes71912644 | Lactate dehydrogenase71912644 | Lactate dehydrogenase71912642 | Lactate dehydrogenase71912643 | Protein71912643 | Protein71912644 | Protein71912642 | BUN71912643 | BUN71912642 | BUN71912644 | Urate71912642 | Urate71912643 | Urate71912644 | Chloride71912644 | Chloride71912643 | Chloride71912642 | Calcium71912642 | Calcium71912643 | Calcium71912644 | Urine specific gravity71912642 | Urine specific gravity71912644 | Urine specific gravity71912643 | Urine pH71912642 | Urine pH71912644 | Urine pH71912643 | Urine glucose71912642 | Urine glucose71912644 | Urine glucose71912643 | Urine ketones71912642 | Urine ketones71912644 | Urine ketones71912643 | Urine nitrite71912642 | Urine nitrite71912643 | Urine nitrite71912644 | Urine leukocyte esterase71912642 | Urine leukocyte esterase71912643 | Urine leukocyte esterase71912644 | Urine erythrocytes71912642 | Urine erythrocytes71912644 | Urine erythrocytes71912643 | Urine leukocytes71912642 | Urine leukocytes71912643 | Urine leukocytes71912644 |
|---|
| Normal | Abnormal low only | Abnormal high only | Abnormal low and abnormal high |
|---|
| Monotherapy Cohort: PF-04449913 25 mg | 2 |
| Monotherapy Cohort: PF-04449913 100 mg | 2 |
| Monotherapy Cohort: PF-04449913 50 mg | 2 |
| Monotherapy Cohort: PF-04449913 100 mg | 4 |
| Monotherapy Cohort: PF-04449913 100 mg | 0 |
| Monotherapy Cohort: PF-04449913 25 mg | 1 |
| Monotherapy Cohort: PF-04449913 100 mg | 1 |
| Monotherapy Cohort: PF-04449913 25 mg | 3 |
| Monotherapy Cohort: PF-04449913 50 mg | 4 |
| Monotherapy Cohort: PF-04449913 100 mg | 5 |
| Monotherapy Cohort: PF-04449913 25 mg | 0 |
| Monotherapy Cohort: PF-04449913 100 mg | 3 |
| Monotherapy Cohort: PF-04449913 50 mg | 3 |
| Monotherapy Cohort: PF-04449913 50 mg | 0 |
| Monotherapy Cohort: PF-04449913 50 mg | 1 |
Median Days to Neutrophil Engraftment
Neutrophil engraftment was recorded as the first day that absolute neutrophil counts (ANC) exceeds 0.5 X 10^9/L for three consecutive readings. (NCT01702961)
Timeframe: 30 days post-transplant
| Intervention | days (Median) |
|---|
| BEAM + R: Autologous Stem Cell Transplant | 11 |
Disease-free Survival
Disease-free survival at 12 months post-transplant in patients with Hodgkin's disease or non-Hodgkin's lymphomas (NCT01702961)
Timeframe: 12 months post-transplant
| Intervention | percentage of participant (Number) |
|---|
| All patients | Hodgkin's Disease | Non-Hodgkin's Lymphomas |
|---|
| BEAM + R: Autologous Stem Cell Transplant | 76 | 88 | 70 |
Number of Participants With Overall Best Response Achieved After Transplantation
Response was summarized as complete remission (CR): disappearance of all evidence of disease; partial remission (PR): regression of measurable disease (>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses) and no new sites; stable disease (SD): failure to attain CR/PR/PD; relapsed disease or progressive disease (PD): any new lesion or increase by >= 50% of previously involved sites from nadir. (NCT01702961)
Timeframe: 3 months post-transplant
| Intervention | participants (Number) |
|---|
| Complete Remission (CR) | Partial Remission (PR) | Stable Disease (SD) | Relapsed Disease or Progressive Disease (PD) |
|---|
| BEAM + R: Autologous Stem Cell Transplant | 63 | 8 | 0 | 4 |
Number of Participants Who Successfully Completed the of Quality of Life Form
Subjects receiving outpatient high dose cytarabine or inpatient high dose cytarabine will complete the European Organization for Research and Treatment of Cancer Quality of Life tool on the last day of each cycle of chemotherapy. It encompasses 5 functional scales, 3 symptom scales and a global health measure. Scores range from 0-100 with higher scores associated with improved quality of life. (NCT02101983)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Outpatient HiDAC Consolidation | 4 |
| Quality of Life Comparison Group | 5 |
Number of Participants With Grades 3 to 5 Non-hematologic Toxicity.
To determine the incidence of number of grades 3 to 5 non-hematologic toxicity of high-dose cytarabine for AML consolidation administered in an outpatient setting. (NCT02101983)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Outpatient HiDAC Consolidation | 4 |
| Quality of Life Comparison Group | 5 |
Number of Patients Achieving Neutrophil Engraftment
Proportion of patients who successfully achieve neutrophil engraftment after stem cell transplant, defined as an absolute neutrophil count of 500/mm3 or for three consecutive days. (NCT02059239)
Timeframe: 35 Days Post-Transplant
| Intervention | Participants (Count of Participants) |
|---|
| Chemo Plus Autologous Transplantation | 16 |
| Chemo Plus Allogeneic Transplantation | 13 |
Number of Patients Achieving Platelet Engraftment
Proportion of patients who successfully achieve platelet engraftment after stem cell transplant, defined as a platelet count of >20k/microL for three consecutive days without transfusion support for seven consecutive days. (NCT02059239)
Timeframe: 74 Days Post-Transplant
| Intervention | Participants (Count of Participants) |
|---|
| Chemo Plus Autologous Transplantation | 16 |
| Chemo Plus Allogeneic Transplantation | 12 |
Progression-Free Survival After Stem Cell Transplant
Time elapsed between stem cell transplant (Day 0) and disease progression, as defined by the Cheson Criteria (the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size) (NCT02059239)
Timeframe: Stem cell transplant (Day 0) up to 2 years post-transplant
| Intervention | Months (Median) |
|---|
| Chemo Plus Autologous Transplantation | NA |
| Chemo Plus Allogeneic Transplantation | 8 |
Transplant-Related Mortality
Death due to any cause other than disease progression within first 100 days post-transplant. (NCT02059239)
Timeframe: From Day 0 until time of death, up to 100 days post-transplant.
| Intervention | Participants (Count of Participants) |
|---|
| Chemo Plus Autologous Transplantation | 0 |
| Chemo Plus Allogeneic Transplantation | 2 |
Disease Response 30 Days Post-Transplant
Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 30 days following autologous or allogeneic stem cell transplant (NCT02059239)
Timeframe: 30 days after stem cell transplant
| Intervention | Participants (Count of Participants) |
|---|
| Complete Remission | Partial Remission | Stable Disease | Progressive Disease | Not Assessed |
|---|
| Chemo Plus Allogeneic Transplantation | 7 | 3 | 1 | 1 | 1 |
,| Chemo Plus Autologous Transplantation | 12 | 2 | 2 | 0 | 0 |
Disease Response at 1 Year Post-Transplant
Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, 1 year following autologous or allogeneic stem cell transplant (NCT02059239)
Timeframe: 1 year after stem cell transplant
| Intervention | Participants (Count of Participants) |
|---|
| Complete Remission | Partial Remission | Stable Disease | Progressive Disease | Not Assessed | Patient Deceased |
|---|
| Chemo Plus Allogeneic Transplantation | 4 | 0 | 0 | 2 | 0 | 7 |
,| Chemo Plus Autologous Transplantation | 12 | 1 | 0 | 3 | 0 | 0 |
Disease Response Following Salvage Chemotherapy
Proportion of patients achieving a complete remission (CR; disappearance of clinically overt disease with no FDG-avid lesions on PET scan), partial remission (PR; reduction in clinical disease buden and >50% bi-dimensional decrease in tumor size on imaging), stable disease (SD; failure to meet the criteria for CR, PR or PD with no new areas of disease involvement) or progressive disease (PD; the appearance of any new lesion >1.5cm in size or a greater than 50% increase in the diameter of a previously identified node of over 1cm in size), as per Cheson Criteria, following salvage chemotherapy with Bendamustine. (NCT02059239)
Timeframe: Within 14 days of salvage chemotherapy treatment
| Intervention | Participants (Count of Participants) |
|---|
| Complete Remission | Partial Remission | Stable Disease | Progressive Disease | Not Assessed |
|---|
| Chemo Plus Allogeneic Transplantation | 1 | 6 | 2 | 6 | 1 |
,| Chemo Plus Autologous Transplantation | 4 | 8 | 4 | 1 | 1 |
Overall Survival at Day 365 Post-Transplant
The time from stem cell infusion (Day 0) to death from any cause. (NCT02059239)
Timeframe: From Day 0 until time of death, assessed up to 365 days post-transplant
| Intervention | Participants (Count of Participants) |
|---|
| Alive | Deceased |
|---|
| Chemo Plus Allogeneic Transplantation | 6 | 7 |
,| Chemo Plus Autologous Transplantation | 16 | 0 |