TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts

PRIMARY OBJECTIVE: I. To establish the recommended phase 2 dose (RP2D) of UAE inhibitor TAK-243 (TAK-243) administered intravenously in a twice-weekly schedule in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). SECONDARY OBJECTIVES: I. To assess the maximum tolerated dose (MTD) evaluated on the first cycle (Day 1 to 21) of TAK-243, its safety profile, and dose limiting toxicities (DLT). II. To investigate preliminary anti-leukemic activity of TAK-243 monotherapy in patients with AML or MDS. III. To describe the pharmacokinetic (PK) profile of TAK-243. IV. To describe the pharmacodynamic (PD) effects of TAK-243. EXPLORATORY OBJECTIVE: I. To investigate associations between clinical responses and molecular/cytogenetic abnormalities in the leukemia cells or to the PK profile or PD effects of TAK-243. OUTLINE: This is a dose-escalation study. Patients receive TAK-243 intravenously (IV) over 30 minutes on days 1, 4, 8, and 11 of each cycle. Cycles repeats every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo urine sample collection, bone marrow aspiration and bone marrow biopsy, multigated acquisition scan (MUGA) and echocardiogram (ECHO) during screening and on study, and blood sample collection throughout the trial. After completion of study treatment, patients are followed up at 30 days.