ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

This study tests a combination of three drugs — ASTX727 (decitabine/cedazuridine), venetoclax, and gilteritinib — for people with a type of leukemia called FLT3-mutated Acute Myeloid Leukemia (AML) that is either newly diagnosed in patients who cannot tolerate intensive chemotherapy, or has come back after previous treatment. **You may be eligible if...** - You are 18 or older with AML that has an FLT3 gene mutation - You are newly diagnosed and ineligible for intensive chemotherapy (due to age 75+, heart problems, reduced lung function, or frailty) - OR your AML has relapsed or not responded to prior treatment (Phase I cohort) - You also qualify if you have high-risk myelodysplastic syndrome (MDS) and are in the Phase I portion **You may NOT be eligible if...** - Your AML does not have an FLT3 mutation - You are newly diagnosed but healthy enough for standard intensive chemotherapy (and under 75) - Your organ function does not meet minimum requirements Talk to your doctor to see if this trial is right for you.