This clinical trial is for men and women with newly diagnosed or relapsed/refractory acute myeloid leukemia.

The purpose of this study is to determine a safe dose of an investigational new drug (ziftomenib) in combination with other study drugs i.e., venetoclax and azacitidine or cytarabine plus daunorubicin. This will include an evaluation of side effects associated with ziftomenib in combination with the other study drugs and also aims to determine how ziftomenib works in combination with the other study drugs.

There are certain genetic changes within the leukemia cell thought to drive the disease in patients with acute myeloid leukemia. Certain mutations in the NPM1 gene and rearrangements involving the KMT2A gene (also referred to as the MLL gene) are known to activate the menin pathway that plays a role in AML. Ziftomenib is an investigational drug that blocks the menin pathway in hopes of preventing or slowing the leukemia cells from growing and dividing.

Investigational means that ziftomenib has not yet been approved by the U.S. Food and Drug Administration (FDA). The other study drugs are approved by the FDA but are considered investigational when combined with ziftomenib in this study.

There are two parts to this study. A dose escalation part and a dose-validation expansion part. In both parts of this study, participants will receive ziftomenib in combination with either venetoclax and azacitidine or cytarabine and daunorubicin. There are a number of different study cohorts within each part, and participants will be assigned to a cohort as determined by the study team.
   
Participation will depend on how each participant tolerates the study drugs, how their cancer responds to the treatment, and their overall condition.