PRIMARY OBJECTIVE:~I. To obtain preliminary evidence of efficacy as defined by 1-year progression free survival.~SECONDARY OBJECTIVES:~I.To determine safety of this regimen as per National Cancer Institute (NCI) toxicity criteria.~II.To determine time to neutrophil and platelet engraftment. III.To determine incidence of acute and chronic graft versus host disease (GVHD).~IV.To determine relapse incidence. V.To determine non-relapse mortality. VI.To determine overall survival. VII.To determine graft versus host disease-relapse free survival (GRFS).~OUTLINE:~Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3, busulfan intravenously (IV) over 3 hours on days -20, -13, -6, -5, -4, and -3, and fludarabine phosphate (fludarabine) IV over 1 hour and cladribine IV over 2 hours on days -6 to -3 in the absence of disease progression or unacceptable toxicity. Patients then undergo stem cell transplantation over 1-2 hours on day 0.~After completion of study treatment, patients are followed up at 7 days, at engraftment, at 1, 3, 6, and 12 months, then annually for up to 3 years.
This phase II trial studies the effect of venetoclax together with busulfan, cladribine, and fludarabine in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing stem cell transplant. Chemotherapy drugs, such as venetoclax, busulfan, cladribine, 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. Adding venetoclax to the current standard of care stem cell transplant regimen of busulfan, fludarabine, and cladribine may help to control high-risk acute myeloid leukemia or myelodysplastic syndrome.