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)

Official Title

A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia

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).

Trial Description

Primary Outcome:

  • Event-Free Survival (EFS)
Secondary Outcome:
  • Overall Survival (OS)
  • Six-Month Survival Rate
  • One-Year Survival Rate
  • Thirty-Day Survival Rate
  • Sixty-Day Survival Rate
  • Time to AML Transformation in HR MDS and CMML Participants
  • Percentage of Participants with complete remission (CR) and complete remission with incomplete blood count recovery (CRi)
  • Percentage of Participants with CR and Marrow CR
  • Percentage of Participants with CR, partial remission (PR) and Hematologic Improvement (HI)
  • Percentage of Participants with CR and Marrow CR and PR
  • Percentage of Participants with CR and Marrow CR, PR and Hematologic Improvement (HI)
  • Percentage of Participants with Overall Response (OR)
  • Percentage of Participants with Overall Response 2 (OR2)
  • Duration of CR
  • Duration of Overall Response (OR)
  • Duration of Overall Response 2 (OR2)
  • Percentage of Participants with Red Blood Cells (RBCs) and Platelet-transfusion Independence
  • Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence
  • Time to First CR or PR
  • Percentage of Participants with Hematologic Improvement (HI)
  • Percentage of Participants with at least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML
  • Time to Progressive Disease (PD), Relapse or Death
  • Health-Related Quality of Life (HRQOL) using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30
  • Plasma Concentration of Pevonedistat
  • 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
  • Event-Free Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group
  • Overall Survival in Participants who have TP53 Mutations, 17p Deletions, and/or are Determined to be in an Adverse Cytogenetic Risk Group
  • Percentage of Participants with Overall Response by Cycle 6
The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (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-centre trial will be conducted worldwide. 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 or relapse from CR (for participants with low-blast AML at study enrollment).

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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