PRIMARY OBJECTIVES:~I. To evaluate the safety and tolerability and to determine the dose-limiting toxicity and the maximum tolerated dose MTD of the combination of daunorubicin, cytarabine (7+3) + venetoclax for patients with acute myeloid leukemia (AML) and advanced myelodysplastic syndrome (MDS).~SECONDARY OBJECTIVES:~I. Determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR).~II. Evaluate ability of venetoclax with chemotherapy combination in eliminating leukemic stem cells (LSCs).~OUTLINE: This is a phase I, dose-escalation study of venetoclax in combination with intensive chemotherapy.~INDUCTION THERAPY: Patients receive venetoclax 400mg orally (PO) on days 1-8 or 1-11 or 1-14, daunorubicin IV over 15 minutes on days 2-4, cytarabine IV over 4 hours on days 2-8.~CONSOLIDATION THERAPY: Patients receive venetoclax PO on days 1-7, cytarabine IV over 2 hours every 12 hours on days 1,3 and 5. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
This phase Ib trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or advanced myelodysplastic syndromes. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as daunorubicin, cytarabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with combination chemotherapy may work better in treating patients with acute myeloid leukemia.