NCT03772925

Pevonedistat and Belinostat in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1 Study of MLN4924 (Pevonedistat) and Belinostat in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies side effects and best dose of pevonedistat and belinostat in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as pevonedistat and belinostat, 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.

Detailed description

PRIMARY OBJECTIVE: I. To identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) for a regimen combining MLN4924 (pevonedistat) with belinostat in patients with refractory/relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: I. To describe the toxicities of this regimen. II. To observe and record anti-tumor activity. III. If responses are observed, to determine what relationship, if any, exists between such responses and TP53/FLT3 mutational status. IV. To describe pharmacokinetic (PK) interactions, if any, between MLN4924 (pevonedistat) and belinostat. V. To test the feasibility of performing correlative studies involving nuclear RelA, phosphorylated (p)-ATR, p-Chk1, Cdt-1, gammaH2A.X, p-HH3, ClCasp3, NQO1, SLC7A11, ATF3, B2M, GCLM, GSR, MAG1, RPLP0, SRXN1, TXNRD1, UBC, p-BRCA1, p-FANCD2, Ac-H3K56, Ac-H4K16, p-Wee1, CtIP, BCL-2, BIM, BCL-xL, or MCL-1. OUTLINE: This is a dose-escalation study. Patients receive belinostat intravenously (IV) daily over 30 minutes on days 1-5 and pevonedistat IV once daily (QD) over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 2 months for 2 years.

Conditions

• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Myeloid Leukemia
• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Belinostat	Given IV
DRUG	Pevonedistat	Given IV

Timeline

• Start date: 2019-06-20
• Primary completion: 2022-09-06
• Completion: 2025-05-08
• First posted: 2018-12-12
• Last updated: 2026-03-03
• Results posted: 2026-03-03

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study