NCT03745352

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

A Randomized Phase II Trial of MLN4924 (Pevonedistat) With Azacitidine Versus Azacitidine in Adult Relapsed or Refractory Acute Myeloid Leukemia

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well pevonedistat works with azacitidine compared to azacitidine alone in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if pevonedistat with azacitidine or azacitidine alone may work better in treating patients with acute myeloid leukemia.

Detailed description

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.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV or SC
DRUG	Pevonedistat	Given IV

Timeline

• Start date: 2019-05-20
• Primary completion: 2021-08-19
• Completion: 2021-08-19
• First posted: 2018-11-19
• Last updated: 2023-06-27

Regulatory

• FDA-regulated drug study