Ruxolitinib in Combination With Venetoclax With and Without Azacitidine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Exclusion Criteria

• •Diagnosis of acute promyelocytic leukemia (APL or AML M3 subtype)
• •Active central nervous system involvement with AML
• •Chemotherapy or therapy with a non-investigational agent other than a biologic intended to within 1 week of the planned start of study therapy, with the exception of hydroxyurea for cytoreduction of proliferative disease, or at the discretion of the principal investigator (PI)
• •Therapy with a non-biologic investigational agent within 14 days or 5 half lives, whichever is longer, of the planned start of study therapy, or for the period recommended by the institution's research pharmacy service, or at the discretion of the PI
• •Therapy with a biologic investigational or non-investigational agent (e.g., monoclonal antibody) within 30 days of the planned start of study therapy, or for the period recommended by the institution's research pharmacy service, or at the discretion of the PI
• •Concurrent active malignancy with expected survival of less than 1 year, at the discretion of the investigator. For example, candidates with treated skin cancers, prostate cancer, breast cancer, etc. without metastatic disease are candidates for therapy since their expected survival exceeds that of relapsed or refractory AML
• •Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period
• •Participants with rapidly progressive disease (defined by blast count doubles within 48 hours) or organ dysfunction
• •Documented cardiac insufficiency (e.g., symptomatic heart failure, left ventricular ejection fraction of ≤ 40%)
• •Symptomatic shortness of breath or patient requires supplemental oxygen support
• •Clinically significant coagulation abnormality, such as disseminated intravascular coagulation
• •Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment
• •Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (hepatitis C virus \[HCV\]), chronic active hepatitis B (hepatitis B virus \[HBV\]), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis
• •Clinically significant surgery within 2 weeks of enrollment
• •Unwillingness to receive infusion of blood products
• •Requires use of medications interact with study drug and that cannot be terminated or adjusted. Use of the following therapies requires review by the sponsor investigator:
• •* Strong and moderate CYP3A inhibitors
• •* Strong and Moderate CYP3A inducers
• •Patients with uncontrolled white blood cell count (defined as \> 50 K/mm\^3 and not controlled with hydroxyurea)
• •Patients with known sensitivity to ruxolitinib, venetoclax, or azacitidine
• •Since it is unknown whether ruxolitinib, venetoclax, or azacitidine (or their metabolites) are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant, breastfeeding concurrent with study participation is prohibited