PRIMARY OBJECTIVES:~I. To determine the safety and toxicity profile of combination therapy of prexasertib (LY2606368), fludarabine and cytarabine in patients with relapsed or refractory (first or second salvage) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HRMDS).~SECONDARY OBJECTIVES:~I. To determine the complete response (CR), CR with incomplete count recovery (CRi), morphologic leukemia free state (MLFS) and partial response (PR) rates.~II. To determine the duration of response. III. To determine the disease-free survival. IV. To determine the overall survival with combination therapy of LY2606368, fludarabine and cytarabine in patients with relapsed or refractory AML/HRMDS.~V. To determine the correlative studies including but not limited to total and phosphor histone (H2AX), checkpoint kinase-2 (Chk1), checkpoint kinase-2 (Chk2), ras protein specific guanine nucleotide releasing factor 1 (Cdc25), retinoblastoma-associated protein (Rb), cyclin-dependent kinase (CDK), protein kinase B (AKT) in AML cells by flow cytometry and/or Western blot.~OUTLINE: This is a dose-escalation study of prexasertib (LY2606368).~Patients =/< 65 years of age: receive fludarabine intravenously (IV) over approximately 2 hours on days 1-4, cytarabine IV over 4 hours on days 1-4, and prexasertib (LY2606368) IV over approximately 2 hours on days 1, 3, and 4 or on days 1-4.~Patients > 65 years of age: receive fludarabine IV over approximately 2 hours on days 1-3, cytarabine IV over 4 hours on days 1-3, and prexasertib (LY2606368) IV over approximately 2 hours on days 1, 3, and 4 or on days 1-4. Treatment for both age groups repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients in remission who do not start new treatment are followed up every 2-3 months for up to 2 years.
This phase I trial studies the side effects and determine the best dose of prexasertib (LY2606368) when given together with cytarabine and fludarabine in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement or no longer responds to treatment. Prexasertib (LY2606368) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving prexasertib (LY2606368) together with cytarabine and fludarabine may work better in treating patients with acute myeloid leukemia or myelodysplastic syndrome.