This is a phase 1 study to determine the safety, dosing schedule and recommended phase 2 dose of a triplet therapy with navitoclax, venetoclax, and decitabine for patients with the four high-risk myeloid malignancy subgroups of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MDS/MPN) and myelofibrosis accelerated phase (MF-AP).~The U.S. Food and Drug Administration (FDA) has not approved the combination of venetoclax, navitoclax, and decitabine navitoclax as a treatment for any disease.The FDA has approved the combination of venetoclax and decitabine for acute myeloid leukemia (AML) and decitabine given alone is approved for myelodysplastic syndrome (MDS).~The research study procedures include screening for eligibility, study treatments, and blood tests and bone marrow biopsies to assess response to treatment.~Participants will receive the study treatment regimen as long as it is effective.~It is expected that about 36 people will take part in this research study.~AbbVie, a pharmaceutical company, is supporting this research study by providing funding and the study drugs navitoclax and venetoclax.
The purpose of this research study is to test the safety of a new three drug combination of navitoclax, decitabine, and venetoclax to treat advanced myeloid malignancies.~The names of the drugs involved in this study are:~Venetoclax~Decitabine~Navitoclax