This phase II MyeloMATCH treatment trial studies how well ASTX727 and venetoclax plus enasidenib works compared to ASTX727 and venetoclax alone for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML) or younger patients who are considered unfit for standard treatment, and who have an abnormal change (mutation) in the IDH2 gene. This gene mutation can cause AML to grow and spread. This trial is being done to see if adding enasidenib to the usual treatment can help more patients with the IDH2 gene get rid of AML. ASTX727 is a fixed-dose formulation of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Enasidenib works by stopping the growth and spread of tumor cells that have the IDH2 mutation. Giving ASTX727 and venetoclax plus enasidenib may work better in treating AML patients with the IDH2 mutation.
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Minimal residual disease negative (MRDneg) complete remission (CR) rate
Timeframe: Baseline to 5 years