Pevonedistat With Azacitidine Versus Azacitidine Alone in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

PRIMARY OBJECTIVE: I. To compare overall survival (OS) of MLN4924 (pevonedistat) and azacitidine in combination versus azacitidine alone. SECONDARY OBJECTIVE: I. To compare the overall response rate (ORR) and duration of response (DOR) of MLN4924 (pevonedistat) and azacitidine in combination versus azacitidine alone. EXPLORATORY OBJECTIVES: I. To compare the rate of early mortality, rate of allogeneic hematopoietic cell transplantation (HCT) and time to response of patients treated with MLN4924 (pevonedistat) and azacitidine versus azacitidine alone. II. To determine whether nuclear erythroid 2‐related factor 2 (NRF2) target gene expression is a biomarker of MLN4924 (pevonedistat) activity and predictive of treatment response. III. To correlate cytogenetic and molecular abnormalities and additional potential biomarkers with treatment activity and response. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 3, and 5 and azacitidine IV over 10‐40 minutes or subcutaneously (SC) on either days 1‐7, or days 1‐5 and 8‐9, or days 1‐6 and 8. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive azacitidine IV or SC as in Arm A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, then every 6 months thereafter.