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

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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 ...

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, 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) once daily (QD) over 30 minutes on days 1-5 and pevonedistat IV 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.

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