PANTHER: Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine. (An event is defined as death or transformation to AML in participants with MDS or CMML, whichever occurs first, and is defined as death in participants with low-blast AML).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment with azacitidine. This study will look at the overall survival, event-free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine.
The study will enroll approximately 450 participants. Once enrolled, participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles:
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Pevonedistat 20 mg/m2 and azacitidine 75 mg/m2 combination
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Single-agent azacitidine 75 mg/m^2
All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion.
This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic, France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland, Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner.
Participants with HR MDS or CMML will have EFS follow-up study visits every month if their disease has not transformed to AML and they have not started subsequent therapy. Participants with low-blast AML will have response follow-up study visits every month until they relapse from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted every 3 months) when they have confirmed transformation to AML (for participants with HR MDS or CMML at enrollment) or experienced PD (for participants with low-blast AML at study enrollment).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Azacitidine + Pevonedistat Azacitidine 75 milligram per square meter (mg/m^2), intravenous or subcutaneous, on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2, 60-minute (+/-10) infusion, intravenous, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity. |
Drug: Azacitidine
Azacitidine intravenous or subcutaneous formulation.
Drug: Pevonedistat
Pevonedistat intravenous infusion.
|
| Experimental: Azacitidine Azacitidine 75 mg/m^2, intravenous or subcutaneous, on Days 1 to 5, Days 8 and 9 in 28-day treatment cycles until disease progression or unacceptable toxicity. |
Drug: Azacitidine
Azacitidine intravenous or subcutaneous formulation.
|
Outcome Measures
Primary Outcome Measures
- Event-Free Survival (EFS) [From randomization until transformation to acute myeloid leukemia, or death due to any cause : up to 6 years]
EFS is defined as the time from randomization to the date of an EFS event. An EFS event is defined as death or transformation to AML (World Health Organization [WHO] classification as a participant having greater than (>) 20 percent (%) blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurs first, in participants with MDS or CMML. An EFS event is defined as death in participants with low-blast AML.
Secondary Outcome Measures
- Overall Survival (OS) [From randomization until death : up to 6 years]
OS is calculated as the time from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis will be censored as of the date the participant was last known to be alive.
- Six-Month Survival Rate [Month 6]
Six-month survival rate is defined as Kaplan-Meier estimate of six-month survival rate.
- One-Year Survival Rate [Month 12]
One-year survival rate is defined as Kaplan-Meier estimate of one-year survival rate.
- Thirty-Day Survival Rate [Day 30]
Thirty-day survival rate is defined as Kaplan-Meier estimate of thirty-day survival rate.
- Sixty-Day Survival Rate [Day 60]
Sixty-day survival rate is defined as Kaplan-Meier estimate of sixty-day survival rate.
- Time to AML Transformation in HR MDS, HR CMML and HR MDS/CMML Participants [From randomization until transformation to AML : up to 6 years]
Time to AML transformation in HR MDS and CMML participants is defined as time from randomization to documented AML transformation. Participants who died before progression to AML will be censored. Transformation to AML is defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.
- Percentage of Participants with Complete Remission (CR) and CR+Complete Remission with Incomplete Blood Count Recovery (CRi) [From randomization until CR: up to 6 years]
CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
- Percentage of Participants with CR and Marrow CR [From randomization until CR or marrow CR : up to 6 years]
Disease responses for HR MDS or CMML are based on the IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and >=11 g/dL Hgb, >=100*10^9/L platelets (pl), >=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment.
- Percentage of Participants with CR, Partial Remission (PR) and Hematologic Improvement (HI) [From randomization until, CR, PR or HI : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. HI: Hgb increase (inc) >=1.5 g/dL if baseline less than (<)11 g/dL; pl inc >=30*10^9/L if baseline>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.
- Percentage of Participants with CR and Marrow CR and PR [From randomization until CR or Marrow CR and PR : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%.
- Percentage of Participants with CR and Marrow CR, PR and Hematologic Improvement (HI) [From randomization until CR, marrow CR, PR or HI : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood. Marrow CR: Bone marrow: <=5% myeloblasts and decrease by >=50% over pretreatment. PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. HI: Hgb increase (inc) >=1.5 g/dL if baseline <11 g/dL; pl inc >=30*10^9/L if baseline>20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.
- Percentage of Participants with Overall Response (OR) [From randomization until CR and PR or CR, CRi and PR : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR or PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils, 0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still>5%. For low-blast AML-CR:morphologic leukemia-free state>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in bone marrow aspirate.
- Percentage of Participants with Overall Response 2 (OR2) [From randomization until, CR, PR or HI or CR, CRi or PR : up to 6 years]
Overall response 2=CR, PR or HI for HR MDS/CMML and CR, CRi or PR for low-blast AML. For HR MDS/CMML-CR: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%;HI: Hgb increase (inc) >=1.5 g/dL if baseline <11 g/dL; pl inc >=30*10^9/L if baseline >20*10^9/L or inc from <20*10^9/L to >20*10^9/L and by 100%; and neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <100*10^9/L. For low-blast AML-CR: morphologic leukemia-free state >1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L;PR: all CR hematological values but >=50% decrease in bone marrow aspirate.
- Duration of CR [From CR until first documentation of PD or relapse from CR or relapse after CR or PR : up to 6 years]
Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML)or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
- Duration of CR+CRi [From CR until first documentation of PD or relapse from CR or relapse after CR or PR : up to 6 years]
Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML)or relapse after CR or PR (participants with HR MDS/CMML). Disease responses for HR MDS or CMML are based on the Modified IWG Response Criteria for MDS and for low-blast AML on the Revised IWG Response Criteria for AML. CR for HR MDS or CMML is defined as <=5% myeloblasts with normal maturation of all cell lines in the bone marrow, and greater than or equal to >=11 g/dL hemoglobin (Hgb),>=100*10^9/liter (/L) platelets (pl),>=1.0*10^9/L neutrophils and 0% blasts in peripheral blood. CR for low-blast AML: morphologic leukemia-free state, neutrophils of more than 1.0*10^9/L and pl of >=100*10^9/L, transfusion independence, and no residual evidence of extramedullary leukemia. CR with incomplete blood count recovery (CRi) for low-blast AML: participants fulfill all of the criteria for CR except for residual neutropenia (<1.0*10^9/L) or thrombocytopenia (pl<100*10^9/L).
- Duration of Overall Response (OR) [From CR or PR or CR, CRi or PR to the first documented PD or relapse from CR (in participants with low-blast AML) or relapse after CR or PR (in participants with HR MDS/CMML): up to 6 years]
Duration of OR: response to first documentation of PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML. Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR+PR for HR MDS/CMML and CR+Cri+ PR for low-blast AML.CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR:all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still >5%. For low-blast AML-CR: morphologic leukemia-free state >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with CRi: fulfill CR criteria except residual neutropenia <1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but >=50% decrease in % of blasts in bone marrow aspirate.
- Duration of Overall Response 2 (OR2) [From documented CR, PR or HI to the first documented PD or relapse from CR (in participants with low-blast AML) or relapse after CR or PR (in participants with HR MDS/CMML): up to 6 years]
Duration of OR2:response to first documented PD or relapse from CR for low-blast AML or relapse after CR or PR for HR MDS/CMML.OR2=CR,PR,HI for MDS/CMML and CR,CRi,PR for low-blast AML. For HR MDS/CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb, >=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment, still >5%; HI: Hgb inc >=1.5 g/dL if baseline <11 g/dL; pl inc>=30*10^9/L if baseline>20*10^9/L or inc from<20*10^9/L to>20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L;PR:all CR hematological values but>=50% decrease in bone marrow aspirate
- Percentage of Participants with Red Blood Cells (RBCs) and Platelet-transfusion Independence [8 weeks before the first dose of study drug through 30 days after last dose of any study drug : up to 6 years]
A participant is defined as RBC or platelet-transfusion independent if he/she receives no RBC or platelet transfusions for a period of at least 8 weeks before the first dose of study drug through 30 days after the last dose of any study drug. Rate of transfusion independence is defined as number of participants who become transfusion independent divided by the number of participants who are transfusion dependent at Baseline.
- Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence [8 weeks before the first dose of study drug through 30 days after last dose of any study drug : up to 6 years]
Duration of RBC and Platelet transfusion independence is defined as the longest time between the last RBC and/or platelet transfusion before the start of the RBC and/or Platelet transfusion-independent period and the first RBC and/or Platelet transfusion after the start of the transfusion-independent period, which occurs>= 8 weeks later.
- Time to First CR or PR or CRi [From randomization until CR or PR : up to 6 years]
Time to first CR or PR is defined as the time from randomization to first documented CR or PR, whichever occurs first. Disease responses for HR MDS or CMML or low-blast AML cycle 6 are based on Modified IWG Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. For HR MDS or CMML-CR:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11 g/dL Hgb,>=100*10^9/L pl,>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood; PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%; For low-blast AML-CR: morphologic leukemia-free state,>1.0*10^9/L neutrophils, pl>=100*10^9/L, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery: fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl <100*10^9/L; PR: all CR hematological values but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
- Percentage of Participants with Hematologic Improvement (HI) [From randomization until HI : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase (inc)>=1.5 g/dL if baseline <11 g/dL; pl inc >=30*10^9/L if baseline >20*10^9/L or inc from <20*10^9/L to >20*10^9/L by at least 100%; neutrophil inc by 100% and absolute inc of >0.5*10^9/L if baseline <1.0*10^9/L.
- Percentage of Participants with at least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML [From randomization until transformation to AML or until initiation of subsequent therapy up to approximately up to 6 years]
Inpatient hospital admission data will be collected through transformation to AML (HR MDS/CMML participants) or disease progression (low-blast AML participants) or until initiation of subsequent therapy (all participants), whichever occurs first. Transformation to AML is defined, according to WHO Classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.
- Time to Progressive Disease (PD), Relapse after CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death [From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first (up to 6 years)]
Time to PD, relapse after CR(low-blast AML), relapse after CR or PR(HR MDS/CMML), or death,defined as time from date of randomization until date of first documentation of PD,relapse after CR(low-blast AML),relapse after CR or PR(HR MDS/CMML),or death due to any cause, whichever occurs first. In HR MDS/CMML,PD: Participants with<5% blasts:>=50% inc >5% blasts, with 5%-9% blasts:>=50% inc>10% blasts, with 10%-19% blasts:>=50% inc >20% blasts,with 20%-30% blasts, at least 50% decrement from maximum remission/response in granulocytes or pl or reduction in Hgb by>=2 g/dL/new transfusion dependence.Relapse after CR or PR: return to pretreatment bone marrow blast %/Decrement of >=50% from maximum remission/response levels in granulocytes/pl/reduction in Hgb conc.>=1.5 g/dL/transfusion dependence. In AML,PD:>50% inc in bone marrow blasts to >30% blasts,>50% inc in circulating blasts to>30% blasts in peripheral blood, Development of extramedullary disease/new sites of extramedullary leukemia.
- Health-Related Quality of Life (HRQOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 [Baseline Up to 6 years]
The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
- Plasma Concentration of Pevonedistat [Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose]
- Percentage of Participants with Overall Response in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group [From randomization until CR, CRi and PR : up to 6 years]
Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS; for low-blast AML on Revised IWG Response Criteria for AML. Overall response=CR + PR for HR MDS/CMML and CR + CRi + PR for low-blast AML. CR for HR MDS/CMML: <=5% myeloblasts with normal maturation of all bone marrow cell lines, >=11 g/dL Hgb, >=100*10^9/L pl, >=1.0*10^9/L neutrophils,0% blasts in peripheral blood and PR: all CR criteria met except bone marrow blasts>=50% decrease over pretreatment but still>5%. For low-blast AML-CR: morphologic leukemia-free state, >1.0*10^9 neutrophils,>=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia; CR with incomplete blood count recovery (CRi): fulfill CR criteria except residual neutropenia<1.0*10^9/L or pl<100*10^9/L; PR: all CR hematological values but>=50% decrease in the percentage of blasts to 5% to 25% in bone marrow aspirate.
- Event-Free Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group [From randomization until transformation to AML if eligible or death : up to 6 years]
Event is defined as death or transformation to AML in participants with MDS or CMML, which ever occurs first. Transformation to AML is defined, according to world health organization (WHO) Classification as a participant having >20% blasts in the blood or marrow and increase of blast count by 50%. Event is defined as death in participants with low-blast AML.
- Overall Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group [From randomization until death : up to 6 years]
OS is calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis will be censored as of the date the participant was last known to be alive.
- Percentage of Participants with Overall Response by Cycle 6 [Up to Cycle 6 (up to approximately Day 168)]
Responses for HR MDS/CMML are based on Modified International Working Group (IWG) Response Criteria for MDS and for low-blast AML on Revised IWG Response Criteria for AML. Overall response=complete remission(CR)and partial remission(PR)for HR MDS/CMML and CR+CR with incomplete blood count recovery(CRi)+PR for low-blast AML. CR for HR MDS/CMML:<=5% myeloblasts with normal maturation of all bone marrow cell lines,>=11g/dL hemoglobin (Hgb),>=100*10^9/L platelet (pl),>=1.0*10^9/L neutrophils, 0% blasts in peripheral blood, and PR:all CR criteria met except bone marrow blasts >=50% decrease over pretreatment but still >5%. For low-blast AML-CR:morphologic leukemia-free state,>1.0*10^9 neutrophils, >=100*10^9/L pl, transfusion independence, no residual evidence of extramedullary leukemia;CRi:fulfill CR criteria except residual neutropenia <1.0*10^9/L/thrombocytopenia (pl<100*10^9/L); PR:all CR hematological values but>=50% decrease in percentage of blasts to 5%-25% in bone marrow aspirate.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML (i.e., with white blood cell [WBC] <13,000/microliter [mcL]) or low-blast acute myelogenous leukemia (AML).
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Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
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Very high (>6 points).
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High (>4.5-6 points).
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Intermediate (>3-4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
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Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
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Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.
Calculation of TRM score:
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0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >=71 years).
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- 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).
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- 0 for (platelets <50), +1 for (platelets >=50).
Exclusion Criteria:
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Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
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Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
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Participants with AML with a WBC count >50,000/mcL. Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria.
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Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:
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Age >75.
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Comorbidities.
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Inability to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM >=4).
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Physician decision (e.g., lack of available stem cell donor).
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The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
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Has either clinical evidence of or history of central nervous system involvement by AML.
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Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
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Is diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease.
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Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
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Has prothrombin time (PT) or aPTT >1.5× upper limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment.
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Has known human immunodeficiency virus (HIV) seropositive.
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Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
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Has known hepatic cirrhosis or severe preexisting hepatic impairment.
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Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension.
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Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Southern Cancer Center - USOR | Daphne | Alabama | United States | 36526 |
| 2 | Southern Cancer Center - USOR | Mobile | Alabama | United States | 36607 |
| 3 | Southern Cancer Center - USOR | Mobile | Alabama | United States | 36608 |
| 4 | Southern Cancer Center- USOR | Mobile | Alabama | United States | 36608 |
| 5 | Southeastern Regional Medical Center - CTCA - PPDS | Goodyear | Arizona | United States | 85338 |
| 6 | Arizona Oncology Associates (Orange HOPE) - USOR | Tucson | Arizona | United States | 85704 |
| 7 | Arizona Oncology Associates (Rudasill HOPE) - USOR | Tucson | Arizona | United States | 85704 |
| 8 | Arizona Oncology Associates (Wilmot HOPE) - USOR | Tucson | Arizona | United States | 85711 |
| 9 | Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc | Corona | California | United States | 92879 |
| 10 | Compassionate Cancer Care Medical Group Inc | Fountain Valley | California | United States | 92708 |
| 11 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
| 12 | Emad Ibrahim, MD, Inc | Redlands | California | United States | 92373 |
| 13 | Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc | Riverside | California | United States | 92501 |
| 14 | Rocky Mountain Cancer Centers (Aurora) - USOR | Aurora | Colorado | United States | 80012 |
| 15 | Rocky Mountain Cancer Centers (Boulder) - USOR | Boulder | Colorado | United States | 80303 |
| 16 | Rocky Mountain Cancer Centers (Colorado Springs) - USOR | Colorado Springs | Colorado | United States | 80907 |
| 17 | Quest Diagnostics, INC | Denver | Colorado | United States | 80209 |
| 18 | Colorado Blood Cancer Institute - PPDS | Denver | Colorado | United States | 80218 |
| 19 | Presbyterian Saint Lukes Medical Center Laboratory | Denver | Colorado | United States | 80218 |
| 20 | Presbyterian/St. Luke's Medical Center | Denver | Colorado | United States | 80218 |
| 21 | Rocky Mountain Cancer Centers (Williams) - USOR | Denver | Colorado | United States | 80218 |
| 22 | Rocky Mountain Cancer Centers (Denver) - USOR | Denver | Colorado | United States | 80220 |
| 23 | Kaiser Foundation Health Plan | Denver | Colorado | United States | 80239 |
| 24 | Laboratory Corporation of America | Englewood | Colorado | United States | 80112 |
| 25 | Rocky Mountain Cancer Centers (Lakewood) - USOR | Lakewood | Colorado | United States | 80228 |
| 26 | Rocky Mountain Cancer Centers (Littleton) - USOR | Littleton | Colorado | United States | 80120 |
| 27 | Rocky Mountain Cancer Centers (Lone Tree) - USOR | Lone Tree | Colorado | United States | 80124 |
| 28 | Rocky Mountain Cancer Centers (Longmont) - USOR | Longmont | Colorado | United States | 80501 |
| 29 | Rocky Mountain Cancer Centers (Parker) - USOR | Parker | Colorado | United States | 80138 |
| 30 | Rocky Mountain Cancer Centers (Pueblo) - USOR | Pueblo | Colorado | United States | 81008 |
| 31 | Rocky Mountain Cancer Centers (Thornton) - USOR | Thornton | Colorado | United States | 80260 |
| 32 | Medstar Research Institute | Washington | District of Columbia | United States | 20010 |
| 33 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Altamonte Springs | Florida | United States | 32701 |
| 34 | SCRI Florida Cancer Specialists South | Bonita Springs | Florida | United States | 34135 |
| 35 | SCRI Florida Cancer Specialists South | Bradenton | Florida | United States | 34209 |
| 36 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Brandon | Florida | United States | 33511 |
| 37 | SCRI Florida Cancer Specialists South | Cape Coral | Florida | United States | 33914 |
| 38 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Clearwater | Florida | United States | 33761 |
| 39 | SCRI Florida Cancer Specialists South | Fort Myers | Florida | United States | 33905 |
| 40 | SCRI Florida Cancer Specialists South | Fort Myers | Florida | United States | 33908 |
| 41 | SCRI Florida Cancer Specialists South | Fort Myers | Florida | United States | 33916 |
| 42 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Gainesville | Florida | United States | 32605 |
| 43 | Mayo Clinic Jacksonville - PPDS | Jacksonville | Florida | United States | 32224 |
| 44 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Largo | Florida | United States | 33770 |
| 45 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Lecanto | Florida | United States | 34461 |
| 46 | University of Miami Miller School of Medicine | Miami | Florida | United States | 33136 |
| 47 | Baptist Health System (N Kendall) - USOR | Miami | Florida | United States | 33176 |
| 48 | SCRI Florida Cancer Specialists South | Naples | Florida | United States | 34102 |
| 49 | Florida Cancer Specialists - NORTH - SCRI - PPDS | New Port Richey | Florida | United States | 34655 |
| 50 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Ocala | Florida | United States | 34471 |
| 51 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Orange City | Florida | United States | 32763 |
| 52 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Orlando | Florida | United States | 32806 |
| 53 | SCRI Florida Cancer Specialists South | Port Charlotte | Florida | United States | 33980 |
| 54 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Saint Petersburg | Florida | United States | 33705 |
| 55 | SCRI Florida Cancer Specialists South | Sarasota | Florida | United States | 34232 |
| 56 | SCRI Florida Cancer Specialists South | Sarasota | Florida | United States | 34236 |
| 57 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Spring Hill | Florida | United States | 34608 |
| 58 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Tampa | Florida | United States | 33607 |
| 59 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Tavares | Florida | United States | 32778 |
| 60 | Florida Cancer Specialists - NORTH - SCRI - PPDS | The Villages | Florida | United States | 32159 |
| 61 | SCRI Florida Cancer Specialists South | Venice | Florida | United States | 34285 |
| 62 | SCRI Florida Cancer Specialists South | Venice | Florida | United States | 34292 |
| 63 | Cleveland Clinic Florida | Weston | Florida | United States | 33331 |
| 64 | Florida Cancer Specialists - NORTH - SCRI - PPDS | Winter Park | Florida | United States | 32792 |
| 65 | Winship Cancer Institute, Emory University | Atlanta | Georgia | United States | 30322 |
| 66 | Saint Alphonsus Regional Medical Center | Boise | Idaho | United States | 83706 |
| 67 | Saint Alphonsus Caldwell Cancer Care Center | Caldwell | Idaho | United States | 83605 |
| 68 | Saint Alphonsus Medical Center | Nampa | Idaho | United States | 83687 |
| 69 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 70 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
| 71 | Centerpoint Medical Center | Independence | Missouri | United States | 64057 |
| 72 | HCA Midwest Health - SCRI - PPDS | Kansas City | Missouri | United States | 64132 |
| 73 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 74 | Nebraska Cancer Specialists | Omaha | Nebraska | United States | 68130 |
| 75 | New Jersey Hematology Oncology Associates LLC | Brick | New Jersey | United States | 08724 |
| 76 | John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
| 77 | New Jersey Hematology and Oncology | Toms River | New Jersey | United States | 08755 |
| 78 | Weill Cornell Medical Center - Monitoring Location | New York | New York | United States | 10021 |
| 79 | Weill Cornell Medical Center | New York | New York | United States | 10021 |
| 80 | Strong Memorial Hospital | Rochester | New York | United States | 14642 |
| 81 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27599 |
| 82 | Oncology Hematology Care, Inc. | Cincinnati | Ohio | United States | 45211 |
| 83 | Oncology Hematology Care, Inc. | Cincinnati | Ohio | United States | 45230 |
| 84 | Oncology Hematology Care Inc - USOR | Cincinnati | Ohio | United States | 45236 |
| 85 | Oncology Hematology Care Inc - USOR | Cincinnati | Ohio | United States | 45242 |
| 86 | Fairview Hospital | Cleveland | Ohio | United States | 44111 |
| 87 | The Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 88 | Oncology Hematology Care, Inc - Fairfield | Fairfield | Ohio | United States | 45014 |
| 89 | Hillcrest Hospital Cancer Care Center | Mayfield | Ohio | United States | 44124 |
| 90 | St. Luke's Hospital | Bethlehem | Pennsylvania | United States | 18015 |
| 91 | St. Luke's University Health Network | Easton | Pennsylvania | United States | 18045 |
| 92 | Greenville Health System | Easley | South Carolina | United States | 29640 |
| 93 | Greenville Health System | Greenville | South Carolina | United States | 29605 |
| 94 | Greenville Health System Cancer Institute | Greenville | South Carolina | United States | 29615 |
| 95 | Greenville Health System | Greer | South Carolina | United States | 29650 |
| 96 | Greenville Health System | Seneca | South Carolina | United States | 29672 |
| 97 | Greenville Health System | Spartanburg | South Carolina | United States | 29307 |
| 98 | Tennessee Oncology - DICKSON - SCRI - PPDS | Dickson | Tennessee | United States | 37055 |
| 99 | Tennessee Oncology - FRANKLIN - SCRI - PPDS | Franklin | Tennessee | United States | 37067 |
| 100 | Tennessee Oncology - GALLATIN - SCRI - PPDS | Gallatin | Tennessee | United States | 37066 |
| 101 | Tennessee Oncology - SUMMIT - SCRI - PPDS | Hermitage | Tennessee | United States | 37076 |
| 102 | Tennessee Oncology - LEBANON - SCRI - PPDS | Lebanon | Tennessee | United States | 37090 |
| 103 | Tennessee Oncology - MURFREESBORO - SCRI - PPDS | Murfreesboro | Tennessee | United States | 37129 |
| 104 | Sarah Cannon Center for Blood Centers - SCRI - PPDS | Nashville | Tennessee | United States | 37203 |
| 105 | Tennessee Oncolgy - BAPTIST - SCRI - PPDS | Nashville | Tennessee | United States | 37203 |
| 106 | Tennessee Oncology NASH - SCRI - PPDS | Nashville | Tennessee | United States | 37203 |
| 107 | Tennessee Oncology - ST THOMAS WEST - SCRI - PPDS | Nashville | Tennessee | United States | 37205 |
| 108 | Tennessee Oncology SKYLINE - SCRI - PPDS | Nashville | Tennessee | United States | 37207 |
| 109 | Tennessee Oncology - SOUTHERN HILLS - SCRI - PPDS | Nashville | Tennessee | United States | 37211 |
| 110 | Tennessee Oncology - SHELBYVILLE - SCRI - PPDS | Shelbyville | Tennessee | United States | 37160 |
| 111 | Tennessee Oncology - SMYRNA - SCRI - PPDS | Smyrna | Tennessee | United States | 37167 |
| 112 | Texas Oncology (West 38) - USOR | Austin | Texas | United States | 78705 |
| 113 | Texas Oncology (Balcones) - USOR | Austin | Texas | United States | 78731 |
| 114 | Texas Oncology (James Casey) - USOR | Austin | Texas | United States | 78745 |
| 115 | Texas Oncology (Medical City) - USOR | Dallas | Texas | United States | 75230 |
| 116 | Baylor Sammons Cancer Center | Dallas | Texas | United States | 75246 |
| 117 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 118 | Texas Oncology (Tyler) - USOR | Longview | Texas | United States | 75601 |
| 119 | Texas Oncology (E Common) - USOR | New Braunfels | Texas | United States | 78130 |
| 120 | Texas Oncology (Round Rock) - USOR | Round Rock | Texas | United States | 78681 |
| 121 | Texas Oncology - San Antonio Medical Center - USOR | San Antonio | Texas | United States | 78240 |
| 122 | Texas Oncology (Tyler) - USOR | Tyler | Texas | United States | 75702 |
| 123 | Oncology and Hematology Associates of Southwest Virginia (Blacksburg) - USOR | Blacksburg | Virginia | United States | 24060 |
| 124 | University of Virginia | Charlottesville | Virginia | United States | 22903 |
| 125 | Oncology and Hematology Associates of Southwest Virginia (Low Moor) - USOR | Low Moor | Virginia | United States | 24457 |
| 126 | Oncology and Hematology Associates of Southwest Virginia (Roanoke) - USOR | Roanoke | Virginia | United States | 24014 |
| 127 | Oncology and Hematology Associates of Southwest Virginia Inc | Salem | Virginia | United States | 24153 |
| 128 | Oncology and Hematology Associates of Southwest Virginia | Wytheville | Virginia | United States | 24382 |
| 129 | Icon Cancer Care Wesley | Auchenflower | Queensland | Australia | 4066 |
| 130 | Icon Cancer Care Chermside | Chermside | Queensland | Australia | 4032 |
| 131 | Icon Cancer Care South Brisbane | South Brisbane | Queensland | Australia | 4101 |
| 132 | Icon Cancer Care | South Brisbane | Queensland | Australia | 4101 |
| 133 | Icon Cancer Care Southport | Southport | Queensland | Australia | 4215 |
| 134 | Royal Hobart Hospital | Hobart | Tasmania | Australia | 7000 |
| 135 | Liverpool Hospital | Liverpool | Australia | 1871 | |
| 136 | Algemeen Ziekenhuis Klina | Brasschaat | Antwerpen | Belgium | 2930 |
| 137 | CHU UCL Namur asbl - Site Godinne | Yvoir | Namur | Belgium | 5530 |
| 138 | AZ Sint-Jan AV | Brugge | West-Vlaanderen | Belgium | 8000 |
| 139 | Cliniques Universitaires Saint-Luc | Bruxelles | Belgium | 1200 | |
| 140 | UZ Leuven | Leuven | Belgium | 3000 | |
| 141 | Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner | Curitiba | Parana | Brazil | 81520-060 |
| 142 | Liga Norte Riograndense Contra O Cancer | Natal | Rio Grande Do Norte | Brazil | 59075-740 |
| 143 | Centro de Pesquisas Oncologicas | Florianopolis | Santa Catarina | Brazil | 88034-000 |
| 144 | Hospital de Clinicas de Porto Alegre (HCPA) - PPDS | Porto Alegre | Brazil | 90035-903 | |
| 145 | Universidade Federal do Rio de Janeiro - UFRJ | Rio De Janeiro | Brazil | 21941-913 | |
| 146 | Hospital Santa Marcelina | Sao Paulo | Brazil | 08270-120 | |
| 147 | Hospital Santa Marcelina | Sao Paulo | Brazil | 08270-270 | |
| 148 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4 |
| 149 | University of Alberta | Edmonton | Alberta | Canada | T6G 2B7 |
| 150 | Kaye Edmonton Clinic | Edmonton | Alberta | Canada | T6G1Z1 |
| 151 | Saint John Regional Hospital | Saint John | New Brunswick | Canada | E2L 4L2 |
| 152 | Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M4N3M5 |
| 153 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 154 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G2M9 |
| 155 | Xuanwu Hospital Capital Medical University | Beijing | Beijing | China | 100053 |
| 156 | Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences | Tianjin | Tianjin | China | 300020 |
| 157 | Fakultni nemocnice Hradec Kralove | Hradec Kralove | Kralovehradeck Kraj | Czechia | 500 05 |
| 158 | Vseobecna Fakultni Nemocnice V Praze | Prague | Czechia | 128 08 | |
| 159 | Fakultni nemocnice Kralovske Vinohrady | Praha | Czechia | 100 34 | |
| 160 | Hopital Cote de Nacre | Caen | Calvados | France | 14033 |
| 161 | CHU Angers | Angers | Maine-et-Loire | France | 49100 |
| 162 | Centre Hospitalier Le Mans | Le Mans | France | 74000 | |
| 163 | Hopital Saint Louis | Paris | France | 75010 | |
| 164 | Hopital Saint Louis | Paris | France | 75475 | |
| 165 | Universitatsklinikum Tubingen | Tubingen | Baden-Wurttemberg | Germany | 72076 |
| 166 | Universitatsklinikum Leipzig | Leipzig | Sachsen | Germany | 4103 |
| 167 | Universitatsklinikum Carl Gustav Carus an der TU Dresden | Dresden | Germany | 1307 | |
| 168 | Marien Hospital Akademisches Lehrkrankenhaus | Dusseldorf | Germany | 40479 | |
| 169 | Laiko General Hospital of Athens | Athens | Attiki | Greece | 115 27 |
| 170 | Athens General Hospital 'G Gennimatas' | Athens | Attiki | Greece | 11527 |
| 171 | Attikon University General Hospital | Athens | Attiki | Greece | 12462 |
| 172 | University Hospital of Alexandroupolis | Alexandroupolis | Greece | 68100 | |
| 173 | Laiko General Hospital of Athens | Athens | Greece | 11527 | |
| 174 | University General Hospital of Ioannina | Ioannina | Greece | 45500 | |
| 175 | University General Hospital of Larissa | Larissa | Greece | 41110 | |
| 176 | University General Hospital of Patras | Patras | Greece | 26504 | |
| 177 | Georgios Papanikolaou General Hospital of Thessaloniki | Thessaloniki | Greece | 57010 | |
| 178 | Edith Wolfson Medical Center | Holon | Israel | 58100 | |
| 179 | Shaare Zedek Medical Center | Jerusalem | Israel | 91031 | |
| 180 | Hadassah Medical Center PPDS - | Jerusalem | Israel | 91120 | |
| 181 | Galilee Medical Center | Nahariya | Israel | ||
| 182 | ZIV Medical Center | Safed | Israel | 13100 | |
| 183 | Tel Aviv Sourasky Medical Center PPDS | Tel Aviv | Israel | 64239 | |
| 184 | Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi | Bologna | Emilia-Romagna | Italy | 40138 |
| 185 | ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN | Brescia | Lombardia | Italy | 25123 |
| 186 | Azienda Ospedaliera Universitaria Careggi | Firenze | Italy | 50134 | |
| 187 | IRCCS Centro Di Riferimento Oncologico Della Basilicata | Rionero In Vulture (PZ) | Italy | 85028 | |
| 188 | Istituto Clinico Humanitas | Rozzano | Italy | 20089 | |
| 189 | Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino | Torino | Italy | 10126 | |
| 190 | Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital | Fukuyama | Hirosima | Japan | 720-0001 |
| 191 | Hokkaido University Hospital | Sapporo | Hokkaido | Japan | 060 8638 |
| 192 | Fukushima Medical University Hospital | Fukushima-shi | Hukusima | Japan | 960-1295 |
| 193 | Kobe City Medical Center General Hospital | Kobe-City | Hyogo | Japan | 650-0047 |
| 194 | University Hospital, Kyoto Prefectural University of Medicine | Kyoto-shi | Kyoto | Japan | 602-8566 |
| 195 | Kindai University Hospital | Osakasayama | Osaka | Japan | 589-8511 |
| 196 | Saitama Medical Center | Kawagoe | Saitama | Japan | 3508550 |
| 197 | Juntendo University Hospital | Bunkyo | Tokyo | Japan | 113-8431 |
| 198 | NTT Medical Center Tokyo | Shinagawa-ku | Tokyo | Japan | 141-8625 |
| 199 | Kyushu University Hospital | Fukuoka-city | Japan | 812-8582 | |
| 200 | Dokkyo Medical University Hospital | Mibu-Machi | Japan | 321-0293 | |
| 201 | Nagasaki University Hospital | Nagasaki | Japan | 8528102 | |
| 202 | Osaka City University Hospital | Osaka | Japan | 545-8586 | |
| 203 | Yokohama City University Hospital | Yokohama-shi | Japan | 232-0024 | |
| 204 | University of Fukui Hospital | Yoshida-gun | Japan | 910-1193 | |
| 205 | Pusan National University Hospital | Busan | Korea, Republic of | 49241 | |
| 206 | Kyungpook National University Hospital | Daegu | Korea, Republic of | 41944 | |
| 207 | Chonnam National University Hwasun Hospital | Jeonnam | Korea, Republic of | 58128 | |
| 208 | Asan Medical Center - PPDS | Seoul | Korea, Republic of | 5505 | |
| 209 | Samsung Medical Center - PPDS | Seoul | Korea, Republic of | 6351 | |
| 210 | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Korea, Republic of | 6591 | |
| 211 | Hematologica Alta Especialidad S.C. | Huixquilucan | Mexico | 52787 | |
| 212 | Capital Humano para Investigacion Clinica SC | Mexico | Mexico | ||
| 213 | Instytut Hematologii i Transfuzjologii | Warszawa | Mazowieckie | Poland | 02-776 |
| 214 | Uniwersyteckie Centrum Kliniczne, Klinika Hematologii I Transplantologii, Budynek Centrum Medycyny N | Gdansk | Pomorskie | Poland | 80-214 |
| 215 | Uniwersyteckie Centrum Kliniczne | Gdansk | Pomorskie | Poland | 80-952 |
| 216 | Swietokrzyskie Centrum Onkologii | Kielce | Swietokrzyskie | Poland | 25-734 |
| 217 | Centrum Onkologii Ziemi Lubelskiej | Lublin | Poland | 20-090 | |
| 218 | Zaklad Diagnostyki Obrazowej SOR | Opole | Poland | 45-061 | |
| 219 | Szpital Wojewodzki w Opolu | Opole | Poland | 45-372 | |
| 220 | City Clinical Hospital # 40 | Moscow | Russian Federation | 129301 | |
| 221 | North-West Federal Medical Research Center n.a. V.A. Almazov | Saint Petersburg | Russian Federation | 197341 | |
| 222 | Russian Research Institute of Hematology and Blood Transfusion | St. Petersburg | Russian Federation | 191024 | |
| 223 | ICO lHospitalet Hospital Duran i Reynals | LHospitalet de Llobregat | Barcelona | Spain | 8907 |
| 224 | Complejo Asistencial Universitario de Leon | Leon | Castilla Y Leon | Spain | 24071 |
| 225 | Hospital Universitario Vall d'Hebron - PPDS | Barcelona | Spain | 8035 | |
| 226 | Hospital Universitario de La Princesa | Madrid | Spain | 28006 | |
| 227 | Hospital General Universitario Gregorio Maranon | Madrid | Spain | 28009 | |
| 228 | Hospital Universitario Ramon y Cajal | Madrid | Spain | 28034 | |
| 229 | Hospital Universitario La Paz - PPDS | Madrid | Spain | 28046 | |
| 230 | Complejo Asistencial Universitario de Salamanca - H. Clinico | Salamanca | Spain | 37007 | |
| 231 | Hospital Clinico Universitario de Valencia | Valencia | Spain | 46010 | |
| 232 | Hospital Universitari i Politecnic La Fe de Valencia | Valencia | Spain | 46026 | |
| 233 | Gazi University Medical Faculty Gazi Hospital | Ankara | Turkey | 6500 | |
| 234 | Ege University Medical Faculty | Izmir | Turkey | 35100 | |
| 235 | Mersin University Medical Faculty | Mersin | Turkey | 33343 | |
| 236 | Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi | Samsun | Turkey | 55139 | |
| 237 | Namik Kemal University | Tekirdag | Turkey | 59100 | |
| 238 | Karadeniz Technical University Faculty of Medicine | Trabzon | Turkey | 61080 | |
| 239 | Royal Bournemouth Hospital | Bournemouth | Dorset | United Kingdom | BH7 7DW |
| 240 | Maidstone Hospital | Maidstone | Kent | United Kingdom | ME16 9QQ |
| 241 | St Bartholomew's Hospital | London | United Kingdom | EC1A 7BE | |
| 242 | Singleton Hospital - PPDS | Swansea | United Kingdom | SA2 8QA |
Sponsors and Collaborators
- Takeda
- Takeda Development Center Americas, Inc.
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- Pevonedistat-3001
- 2017-000318-40
- U1111-1189-8055
- MOH_2018-02-04_002154
- JapicCTI-183848
- NCI-2017-02059