The drug being tested in this study is called pevonedistat. The study will characterize the PK of pevonedistat, assess the safety, and determine the dose of pevonedistat, in combination with azacitidine, in participants with myelodysplastic syndromes (MDS), CMML and AML who also have severe renal impairment or mild hepatic impairment.
The study will enroll approximately 60 participants. The study will be conducted in 2 parts: Part A (PK run-in and dose escalation phase) and Part B. In Part A, participants will be assigned to one of the 3 treatment groups on the basis of their renal and hepatic function:
- Control Arm (Normal Renal and Hepatic Function)
- Renal Arm (Severe Renal Impairment)
- Hepatic Arm (Mild Hepatic Impairment)
Part A will include pevonedistat PK run-in starting on Day -7, followed by a dose-escalation phase with the combination of pevonedistat and azacitidine starting on Day 1. Eligible participants from Part A will continue treatment in optional Part B with the same treatment received in Part A: pevonedistat in combination with azacitidine.
This multi-center trial will be conducted in the United States and Spain. The overall time to participate in this study is approximately 2.5 years. Participants will attend end of the study visit 30 days after the last dose of study drug or before the start of subsequent therapy, if that occurs sooner for safety follow up.
- acute myeloid leukemia (AML)
- chronic myelomonocytic leukaemia (CMML)
- myelodysplastic syndromes (MDS)