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)

Phase 3

Completed

Conditions: Myelodysplastic Syndrome
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic

Interventions: Drug: Azacitidine
Drug: Pevonedistat

Registration Number: NCT03268954

Lead Sponsor: Takeda

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).

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:

* Pevonedistat 20 mg/m\^2 and azacitidine 75 mg/m\^2 combination

* 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 454

Inclusion Criteria

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).
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):
- Very high (>6 points).
- High (>4.5-6 points).
- 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.
Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
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:

0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >=71 years).
- 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).
- 0 for (platelets <50), +1 for (platelets >=50).

Exclusion Criteria

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.
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.
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.
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:
- Age >75.
- Comorbidities.
- Inability to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM >=4).
- Physician decision (e.g., lack of available stem cell donor).
- The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
Has either clinical evidence of or history of central nervous system involvement by AML.
Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
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.
Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
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.
Has known human immunodeficiency virus (HIV) seropositive.
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.
Has known hepatic cirrhosis or severe preexisting hepatic impairment.
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.
Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azacitidine 75 mg/m^2	Azacitidine	Azacitidine 75 milligram per square meter (mg/m\^2) intravenous (IV) or subcutaneous (SC) injection on Days 1 to 5, Days 8 and 9, in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.
Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	Azacitidine	Azacitidine 75 mg/m\^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m\^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.
Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2	Pevonedistat	Azacitidine 75 mg/m\^2 IV or SC injection on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m\^2 IV infusion, on Days 1, 3, and 5 in 28-day treatment cycles until disease progression or unacceptable toxicity or up to approximately 42 months.

Primary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS)	From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)	EFS was defined as the time from randomization to the date of an EFS event. An EFS event was defined as death or transformation to acute myelogenous leukemia (AML) (World Health Organization \[WHO\] classification as a participant having greater than 20 % blasts in the blood or marrow and an increase of blast count by 50%), whichever event occurred first, in participants with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemias (CMML). An EFS event was defined as death in participants with low-blast AML.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	Overall survival was defined as the time from randomization to death from any cause.
Kaplan-Meier Estimates of Six-Month Survival Rate	Up to Month 6	Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of Month 6 from randomization are presented.
Kaplan-Meier Estimates of One-Year Survival Rate	Up to Year 1	Kaplan-Meier estimates for the probability (expressed as a percentage) of participants that survived at the end of the first year from randomization are presented.
Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)	From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)	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 gram per deciliter (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).
Number of Participants With CR and Marrow CR	From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)	Disease responses for HR MDS or CMML are based on the International Working Group (IWG) Response Criteria for MDS. 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.
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 till data cut-off date: 28 May 2021 (up to approximately 42 months)	Event was defined as death or transformation to AML in participants with MDS or CMML, whichever occurred first. Transformation to AML was 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 was defined as death in participants with low-blast AML.
Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30	Up to Day 30	30-day mortality was defined as number of participants who died within 30 days from the first dose of study drug.
Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60	Up to Day 60	60-day mortality was defined as number of participants who died within 60 days from the first dose of study drug.
Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants	From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)	Time to AML transformation in HR MDS and CMML participants was defined as time from randomization to documented AML transformation as determined by the independent review committee (IRC) assessment. Participants who died before progression to AML were censored. Transformation to AML was defined, according to WHO classification, as a participant having 20% blasts in the blood or marrow and increase of blast count by 50%.
Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)	From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)	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 \>=1.5 g/dL if \<11 g/dL; pl increase \>=30\10\^9/L if baseline\>20\10\^9/L or increase from \<20\10\^9/L to \>20\10\^9/L and by at least 100%; neutrophil increase by 100% and absolute increase of \>0.5\10\^9/L if baseline \<1.0\10\^9/L.
Number of Participants With Overall Response (OR)	From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	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.
Duration of Overall Response (OR)	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	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.
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 till data cut-off date: 28 May 2021 (up to approximately 42 months)	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.
Number of Participants With CR and Marrow CR and PR	From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	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%.
Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)	From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)	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 \>=1.5 g/dL if baseline \<11 g/dL; pl increase \>=30\10\^9/L if baseline\>20\10\^9/L or increases from \<20\10\^9/L to \>20\10\^9/L and by at least 100%; neutrophil increases by 100% and absolute increases of \>0.5\10\^9/L if baseline \<1.0\10\^9/L.
Number of Participants With Overall Response 2 (OR2)	From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	OR2=participant with best overall response of CR+PR+HI in HR MDS/CMML participants,or of CR+CRi+PR in low-blast AML participants.CR:≤5% myeloblasts with normal maturation of all bone marrow(BM)cell lines,≥11g/dL Hgb,≥100\10\^9/L pl,≥1.0\10\^9/L neutrophils,0% blasts in peripheral blood;PR:all CR criteria met except BM blasts ≥50% decrease over pretreatment but still \>5%;HI:Hgb increase(inc) ≥1.5g/dL if baseline(BL)\<11 g/dL;pl inc≥30\10\^9/L if BL\>20\10\^9/L or inc from \<20\10\^9/L to \>20\10\^9/L and by 100%;neutrophil inc by 100%;absolute inc of \>0.5\10\^9/L if BL\<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 BM aspirate.Number of responders determined by independent review committee(IRC) assessment.
Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	Duration of RBC and platelet transfusion independence was 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.
Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)	From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	Duration of CR is first documented CR to the first documentation of PD or relapse from CR (participants with low-blast AML). Disease responses for low-blast AML were based on the Revised IWG Response Criteria for AML. CR 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 Red Blood Cells (RBCs) and Platelet-transfusion Independence	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	A participant was defined as RBC or platelet-transfusion independent if he/she received 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 was defined as number of participants who became transfusion independent divided by the number of participants who were transfusion dependent at Baseline.
Duration of Complete Remission (CR)	From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	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 Hgb,\>=100\10\^9/L 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 2 (OR2)	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	Duration of OR2: from date of first documentation of CR+PR+HI to first documentation of PD/relapse after CR/PR for responders of CR+PR+HI for HR 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.
Number of Participants With Hematologic Improvement (HI)	From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)	Disease responses for HR MDS/CMML based on Modified IWG Response Criteria for MDS. HI: Hgb increase \>=1.5 g/dL if baseline \<11 g/dL; pl increase \>=30\10\^9/L if baseline \>20\10\^9/L or increase from \<20\10\^9/L to \>20\10\^9/L by at least 100%; neutrophil increase by 100% and absolute increase of \>0.5\10\^9/L if baseline \<1.0\10\^9/L.
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 (Cycle length= 28 days)
Number 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 till data cut-off date: 28 May 2021 (up to approximately 42 months)	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.
Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)	From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)	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.
Number 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 till data cut-off date: 28 May 2021 (up to approximately 42 months)	Inpatient hospital admission data was 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 occurred 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%.
Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30	Up to data cut-off date: 28 May 2021 (up to approximately 42 months)	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. The percentage of participants for each parameter score were categorized as improved, stable, and worsened. Only categories with at least one participant with event are reported.
Number 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=CR and 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.
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 till data cut-off date: 28 May 2021 (up to approximately 42 months)	OS was calculated from date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored as of the date the participant was last known to be alive.

Trial Locations

Locations (202): Compassionate Cancer Care Medical Group Inc
🇺🇸
Fountain Valley, California, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Baptist Health System (N Kendall) - USOR
🇺🇸
Miami, Florida, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Oncology Hematology Care, Inc.
🇺🇸
Cincinnati, Ohio, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
CHU Angers
🇫🇷
Angers, Maine-et-Loire, France
Quest Diagnostics, INC
🇺🇸
Denver, Colorado, United States
Presbyterian Saint Lukes Medical Center Laboratory
🇺🇸
Denver, Colorado, United States
Presbyterian/St. Luke's Medical Center
🇺🇸
Denver, Colorado, United States
Rocky Mountain Cancer Centers (Williams) - USOR
🇺🇸
Denver, Colorado, United States
Rocky Mountain Cancer Centers (Denver) - USOR
🇺🇸
Denver, Colorado, United States
Kaiser Foundation Health Plan
🇺🇸
Denver, Colorado, United States
Nebraska Cancer Specialists
🇺🇸
Omaha, Nebraska, United States
Sarah Cannon Center for Blood Centers - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncolgy - BAPTIST - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncology NASH - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncology - ST THOMAS WEST - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncology SKYLINE - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Tennessee Oncology - SOUTHERN HILLS - SCRI - PPDS
🇺🇸
Nashville, Tennessee, United States
Texas Oncology - San Antonio Medical Center - USOR
🇺🇸
San Antonio, Texas, United States
Laboratory Corporation of America
🇺🇸
Englewood, Colorado, United States
Colorado Blood Cancer Institute - PPDS
🇺🇸
Denver, Colorado, United States
Emad Ibrahim, MD, Inc
🇺🇸
Redlands, California, United States
Rocky Mountain Cancer Centers (Lakewood) - USOR
🇺🇸
Lakewood, Colorado, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
Southern Cancer Center - USOR
🇺🇸
Mobile, Alabama, United States
Rocky Mountain Cancer Centers (Colorado Springs) - USOR
🇺🇸
Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers (Boulder) - USOR
🇺🇸
Boulder, Colorado, United States
Rocky Mountain Cancer Centers (Littleton) - USOR
🇺🇸
Littleton, Colorado, United States
Rocky Mountain Cancer Centers (Longmont) - USOR
🇺🇸
Longmont, Colorado, United States
Medstar Research Institute
🇺🇸
Washington, District of Columbia, United States
Rocky Mountain Cancer Centers (Parker) - USOR
🇺🇸
Parker, Colorado, United States
Florida Cancer Specialists - NORTH - SCRI - PPDS
🇺🇸
Winter Park, Florida, United States
Mayo Clinic Jacksonville - PPDS
🇺🇸
Jacksonville, Florida, United States
University of Miami Miller School of Medicine
🇺🇸
Miami, Florida, United States
Saint Alphonsus Caldwell Cancer Care Center
🇺🇸
Caldwell, Idaho, United States
Oncology Hematology Care Inc - USOR
🇺🇸
Cincinnati, Ohio, United States
Weill Cornell Medical Center
🇺🇸
New York, New York, United States
St. Luke's Hospital
🇺🇸
Bethlehem, Pennsylvania, United States
Texas Oncology (Medical City) - USOR
🇺🇸
Dallas, Texas, United States
Tennessee Oncology - SMYRNA - SCRI - PPDS
🇺🇸
Smyrna, Tennessee, United States
Baylor Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Oncology and Hematology Associates of Southwest Virginia (Roanoke) - USOR
🇺🇸
Roanoke, Virginia, United States
Oncology and Hematology Associates of Southwest Virginia Inc
🇺🇸
Salem, Virginia, United States
CHU UCL Namur asbl - Site Godinne
🇧🇪
Yvoir, Namur, Belgium
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Hospital Santa Marcelina
🇧🇷
Sao Paulo, Brazil
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Attikon University General Hospital
🇬🇷
Athens, Attiki, Greece
Kaye Edmonton Clinic
🇨🇦
Edmonton, Alberta, Canada
Liga Norte Riograndense Contra O Cancer
🇧🇷
Natal, Rio Grande Do Norte, Brazil
University General Hospital of Larissa
🇬🇷
Larissa, Greece
Xuanwu Hospital Capital Medical University
🇨🇳
Beijing, Beijing, China
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
🇧🇷
Porto Alegre, Brazil
Vseobecna Fakultni Nemocnice V Praze
🇨🇿
Prague, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿
Hradec Kralove, Kralovehradeck Kraj, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿
Praha, Czechia
Hadassah Medical Center PPDS -
🇮🇱
Jerusalem, Israel
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
🇮🇹
Brescia, Lombardia, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹
Firenze, Italy
Universitatsklinikum Leipzig
🇩🇪
Leipzig, Sachsen, Germany
Hopital Saint Louis
🇫🇷
Paris, France
Centre Hospitalier Le Mans
🇫🇷
Le Mans, France
Universitatsklinikum Tubingen
🇩🇪
Tubingen, Baden-Wurttemberg, Germany
IRCCS Centro Di Riferimento Oncologico Della Basilicata
🇮🇹
Rionero in Vulture, Italy
University Hospital of Alexandroupolis
🇬🇷
Alexandroupolis, Greece
Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino
🇮🇹
Torino, Italy
University General Hospital of Ioannina
🇬🇷
Ioannina, Greece
University General Hospital of Patras
🇬🇷
Patras, Greece
Istituto Clinico Humanitas
🇮🇹
Rozzano, Italy
Fukushima Medical University Hospital
🇯🇵
Fukushima-shi, Hukusima, Japan
Chonnam National University Hwasun Hospital
🇰🇷
Jeongnam, Korea, Republic of
University of Fukui Hospital
🇯🇵
Yoshida-gun, Japan
Hematologica Alta Especialidad S.C.
🇲🇽
Huixquilucan, Mexico
Capital Humano para Investigacion Clinica SC
🇲🇽
Mexico, Mexico
Instytut Hematologii i Transfuzjologii
🇵🇱
Warszawa, Mazowieckie, Poland
Hospital Universitario Vall d'Hebron - PPDS
🇪🇸
Barcelona, Spain
North-West Federal Medical Research Center n.a. V.A. Almazov
🇷🇺
Saint Petersburg, Russian Federation
Hospital Universitario de La Princesa
🇪🇸
Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸
Madrid, Spain
Maidstone Hospital
🇬🇧
Maidstone, Kent, United Kingdom
ICO lHospitalet Hospital Duran i Reynals
🇪🇸
LHospitalet de Llobregat, Barcelona, Spain
Ege University Medical Faculty
🇹🇷
Izmir, Turkey
Mersin University Medical Faculty
🇹🇷
Mersin, Turkey
City Clinical Hospital # 40
🇷🇺
Moscow, Russian Federation
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸
Valencia, Spain
Singleton Hospital - PPDS
🇬🇧
Swansea, United Kingdom
Gazi University Medical Faculty Gazi Hospital
🇹🇷
Ankara, Turkey
Hospital General Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Pusan National University Hospital
🇰🇷
Busan, Korea, Republic of
Kyungpook National University Hospital
🇰🇷
Daegu, Korea, Republic of
Asan Medical Center - PPDS
🇰🇷
Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
Marien Hospital Akademisches Lehrkrankenhaus
🇩🇪
Dusseldorf, Germany
Universitatsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪
Dresden, Germany
Centerpoint Medical Center
🇺🇸
Independence, Missouri, United States
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸
Salamanca, Spain
Hospital Universitario La Paz - PPDS
🇪🇸
Madrid, Spain
Rocky Mountain Cancer Centers (Lone Tree) - USOR
🇺🇸
Lone Tree, Colorado, United States
SCRI Florida Cancer Specialists South
🇺🇸
Venice, Florida, United States
NTT Medical Center Tokyo
🇯🇵
Shinagawa-ku, Tokyo, Japan
Strong Memorial Hospital
🇺🇸
Rochester, New York, United States
Arizona Oncology Associates (Rudasill HOPE) - USOR
🇺🇸
Tucson, Arizona, United States
Southeastern Regional Medical Center - CTCA - PPDS
🇺🇸
Goodyear, Arizona, United States
Southern Cancer Center- USOR
🇺🇸
Mobile, Alabama, United States
Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc
🇺🇸
Riverside, California, United States
Rocky Mountain Cancer Centers (Pueblo) - USOR
🇺🇸
Pueblo, Colorado, United States
Rocky Mountain Cancer Centers (Thornton) - USOR
🇺🇸
Thornton, Colorado, United States
Saint Alphonsus Regional Medical Center
🇺🇸
Boise, Idaho, United States
Cleveland Clinic Florida
🇺🇸
Weston, Florida, United States
Winship Cancer Institute, Emory University
🇺🇸
Atlanta, Georgia, United States
John Theurer Cancer Center
🇺🇸
Hackensack, New Jersey, United States
Weill Cornell Medical Center - Monitoring Location
🇺🇸
New York, New York, United States
New Jersey Hematology and Oncology
🇺🇸
Toms River, New Jersey, United States
Oncology Hematology Care, Inc - Fairfield
🇺🇸
Fairfield, Ohio, United States
Hillcrest Hospital Cancer Care Center
🇺🇸
Mayfield, Ohio, United States
Greenville Health System
🇺🇸
Spartanburg, South Carolina, United States
St. Luke's University Health Network
🇺🇸
Easton, Pennsylvania, United States
Tennessee Oncology - SUMMIT - SCRI - PPDS
🇺🇸
Hermitage, Tennessee, United States
Tennessee Oncology - FRANKLIN - SCRI - PPDS
🇺🇸
Franklin, Tennessee, United States
Tennessee Oncology - DICKSON - SCRI - PPDS
🇺🇸
Dickson, Tennessee, United States
Tennessee Oncology - GALLATIN - SCRI - PPDS
🇺🇸
Gallatin, Tennessee, United States
Tennessee Oncology - LEBANON - SCRI - PPDS
🇺🇸
Lebanon, Tennessee, United States
Tennessee Oncology - MURFREESBORO - SCRI - PPDS
🇺🇸
Murfreesboro, Tennessee, United States
Tennessee Oncology - SHELBYVILLE - SCRI - PPDS
🇺🇸
Shelbyville, Tennessee, United States
Texas Oncology (Tyler) - USOR
🇺🇸
Tyler, Texas, United States
Texas Oncology (E Common) - USOR
🇺🇸
New Braunfels, Texas, United States
Texas Oncology (Round Rock) - USOR
🇺🇸
Round Rock, Texas, United States
Oncology and Hematology Associates of Southwest Virginia (Blacksburg) - USOR
🇺🇸
Blacksburg, Virginia, United States
Oncology and Hematology Associates of Southwest Virginia (Low Moor) - USOR
🇺🇸
Low Moor, Virginia, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Icon Cancer Care Chermside
🇦🇺
Chermside, Queensland, Australia
Icon Cancer Care South Brisbane
🇦🇺
South Brisbane, Queensland, Australia
Oncology and Hematology Associates of Southwest Virginia
🇺🇸
Wytheville, Virginia, United States
Icon Cancer Care
🇦🇺
South Brisbane, Queensland, Australia
Icon Cancer Care Southport
🇦🇺
Southport, Queensland, Australia
Liverpool Hospital
🇦🇺
Liverpool, Australia
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Belgium
Algemeen Ziekenhuis Klina
🇧🇪
Brasschaat, Antwerpen, Belgium
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
🇧🇷
Curitiba, Parana, Brazil
Centro de Pesquisas Oncologicas
🇧🇷
Florianopolis, Santa Catarina, Brazil
Universidade Federal do Rio de Janeiro - UFRJ
🇧🇷
Rio De Janeiro, Brazil
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
🇨🇳
Tianjin, Tianjin, China
Kyushu University Hospital
🇯🇵
Fukuoka-city, Japan
Samsung Medical Center - PPDS
🇰🇷
Seoul, Korea, Republic of
Complejo Asistencial Universitario de Leon
🇪🇸
Leon, Castilla Y Leon, Spain
Hospital Clinico Universitario de Valencia
🇪🇸
Valencia, Spain
St Bartholomew's Hospital
🇬🇧
London, United Kingdom
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Rocky Mountain Cancer Centers (Aurora) - USOR
🇺🇸
Aurora, Colorado, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Texas Oncology (West 38) - USOR
🇺🇸
Austin, Texas, United States
Texas Oncology (Balcones) - USOR
🇺🇸
Austin, Texas, United States
Texas Oncology (James Casey) - USOR
🇺🇸
Austin, Texas, United States
HCA Midwest Health - SCRI - PPDS
🇺🇸
Kansas City, Missouri, United States
Tel Aviv Sourasky Medical Center PPDS
🇮🇱
Tel Aviv, Israel
AZ Sint-Jan AV
🇧🇪
Brugge, West-Vlaanderen, Belgium
UZ Leuven
🇧🇪
Leuven, Belgium
Laiko General Hospital of Athens
🇬🇷
Athens, Greece
Georgios Papanikolaou General Hospital of Thessaloniki
🇬🇷
Thessaloniki, Greece
Edith Wolfson Medical Center
🇮🇱
Holon, Israel
University Hospital, Kyoto Prefectural University of Medicine
🇯🇵
Kyoto-shi, Kyoto, Japan
Juntendo University Hospital
🇯🇵
Bunkyo, Tokyo, Japan
Centrum Onkologii Ziemi Lubelskiej
🇵🇱
Lublin, Poland
Namik Kemal University
🇹🇷
Tekirdag, Turkey
Arizona Oncology Associates (Wilmot HOPE) - USOR
🇺🇸
Tucson, Arizona, United States
Royal Hobart Hospital
🇦🇺
Hobart, Tasmania, Australia
Greenville Health System Cancer Institute
🇺🇸
Greenville, South Carolina, United States
Athens General Hospital 'G Gennimatas'
🇬🇷
Athens, Attiki, Greece
Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital
🇯🇵
Fukuyama, Hirosima, Japan
Kindai University Hospital
🇯🇵
Osakasayama, Osaka, Japan
Dokkyo Medical University Hospital
🇯🇵
Mibu, Japan
Osaka Metropolitan University Hospital
🇯🇵
Osaka, Japan
Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
🇹🇷
Samsun, Turkey
Karadeniz Technical University Faculty of Medicine
🇹🇷
Trabzon, Turkey
Tom Baker Cancer Centre
🇨🇦
Calgary, Alberta, Canada
Kobe City Medical Center General Hospital
🇯🇵
Kobe-City, Hyogo, Japan
Yokohama City University Hospital
🇯🇵
Yokohama-shi, Japan
Swietokrzyskie Centrum Onkologii
🇵🇱
Kielce, Swietokrzyskie, Poland
Shaare Zedek Medical Center
🇮🇱
Jerusalem, Israel
Saint Alphonsus Medical Center
🇺🇸
Nampa, Idaho, United States
Saint John Regional Hospital
🇨🇦
Saint John, New Brunswick, Canada
New Jersey Hematology Oncology Associates LLC
🇺🇸
Brick, New Jersey, United States
Hopital Cote de Nacre
🇫🇷
Caen, Calvados, France
Galilee Medical Center
🇮🇱
Nahariya, Israel
ZIV Medical Center
🇮🇱
Safed, Israel
University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Arizona Oncology Associates (Orange HOPE) - USOR
🇺🇸
Tucson, Arizona, United States
Hokkaido University Hospital
🇯🇵
Sapporo, Hokkaido, Japan
Saitama Medical Center
🇯🇵
Kawagoe, Saitama, Japan
Uniwersyteckie Centrum Kliniczne
🇵🇱
Gdansk, Pomorskie, Poland
Zaklad Diagnostyki Obrazowej SOR
🇵🇱
Opole, Poland
Szpital Wojewodzki w Opolu
🇵🇱
Opole, Poland
Royal Bournemouth Hospital
🇬🇧
Bournemouth, Dorset, United Kingdom
Nagasaki University Hospital
🇯🇵
Nagasaki, Japan
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii I Transplantologii, Budynek Centrum Medycyny N
🇵🇱
Gdansk, Pomorskie, Poland
Russian Research Institute of Hematology and Blood Transfusion
🇷🇺
St. Petersburg, Russian Federation
Icon Cancer Care Wesley
🇦🇺
Auchenflower, Queensland, Australia
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
🇮🇹
Bologna, Emilia-Romagna, Italy