Triple Combination of Pevonedistat and Venetoclax Plus Azacitidine in Adults With Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy

Official Title

A Randomized, Open-label, Controlled, Phase 2 Study of Pevonedistat, Venetoclax, and Azacitidine Versus Venetoclax Plus Azacitidine in Adults With Newly Diagnosed Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy

Summary:

The purpose of this study is to determine whether the combination of pevonedistat + venetoclax + azacitidine improves event-free survival (EFS) compared with venetoclax + azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive chemotherapy.

Trial Description

Primary Outcome:

• Event-Free Survival (EFS)

Secondary Outcome:

• Overall Survival (OS)
• Six-month Survival Rate
• One-year Survival Rate
• Two-year Survival Rate
• Thirty-day Mortality Rate
• Sixty-day Mortality Rate
• Percentage of Participants with Complete Remission (CR)
• Percentage of Participants with Composite Complete Remission (CCR)
• Overall Response Rate (ORR)
• Percentage of Participants with CR + CRh
• Percentage of Participants with Leukemia Response
• Duration of CR
• Duration of CRi
• Duration of CCR
• Percentage of Participants who Failed to Achieve CR or CRi
• Duration of ORR
• Time to First CR
• Time to First CRi
• Time to First PR
• Time to Relapse from CR/CRi or Death
• Health-Related Quality of Life (HRQOL) Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale
• HRQOL Measured by EuroQoL Five Dimensions Five Levels (EQ 5D-5L) Scale
• Plasma Concentration of Pevonedistat
• Percentage of Participants with Red Blood Cells (RBCs) and/or Platelet Transfusion Independence
• Percentage of Participants with Hospitalization

The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people who have AML. This study will compare the improvement in EFS in Arm A: pevonedistat + venetoclax + azacitidine combination arm group when compared with Arm B: venetoclax + azacitidine. The study will enroll approximately 150 patients. Participants will be randomly assigned in 1:1 ratio to one of the two treatment groups in 28-day treatment cycles and which will remain disclosed to the patient and study doctor during the study:

• Pevonedistat 20 mg/m^2 + Venetoclax 400 mg (ramp-up dose, Cycle 1 only: 100-400mg) + Azacitidine 75 mg/m^2

• Venetoclax 400 mg (ramp-up dose, Cycle 1 only: 100-400 mg) + Azacitidine 75 mg/m^2 This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 4 years. 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 who discontinue study treatment without evidence of progressive disease (PD) will enter EFS follow-up or response follow-up (study visits every 3 months) or overall survival follow-up (contacted every 3 months to document subsequent therapies and survival status).

View this trial on ClinicalTrials.gov