A Phase 1 Study of MLN4924 (Pevonedistat) and Belinostat in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
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.
• Patients must have one of the following, histologically or cytologically confirmed:
‣ AML (non- acute promyelocytic leukemia \[APL\] AML)
• AML that is relapsed or refractory to at least one prior line of therapy
⁃ MDS, must meet all of the following at the time of enrollment:
• Higher risk MDS (intermediate-2 or high risk by the original International Prognostic Scoring System \[IPSS\]), and
∙ Relapsed, refractory, or intolerant to at least one prior line of therapy containing a hypomethylating agent (deoxyribonucleic acid \[DNA\] methyltransferase inhibitor)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Total bilirubin =\< upper limit of normal (ULN) for the laboratory except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =\< 1.5 x ULN for the laboratory of the direct bilirubin
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
• Creatinine clearance within normal limits for the laboratory OR estimated glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 appropriate to race for patients with creatinine levels above institutional normal
• Known human immunodeficiency virus (HIV) positive patients who meet the following criteria will be considered eligible:
‣ CD4 count \> 350 cells/mm\^3
⁃ Undetectable viral load
⁃ Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents
⁃ No history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy, if indicated
• If history of hepatitis C virus (HCV) infection, patients must be treated and have an undetectable HCV viral load
• The effects of belinostat and/or MLN4924 (pevonedistat) on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitors and NEDD8-activating enzyme (NAE) inhibitory agents are known to be teratogenic, women of child-bearing potential and men must use 1 highly effective method and 1 additional (barrier) method of contraception at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN4924 (pevonedistat) and belinostat administration
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible