Ruxolitinib and Venetoclax in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

Ability to understand and the willingness to sign a written informed consent document
Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included
Morphologically documented relapsed/refractory acute myeloid leukemia (AML) as defined by World Health Organization (WHO) criteria after at least 1 prior therapy for AML with the exception of hydroxyurea. Patients with myelodysplastic syndrome (MDS) transformed to AML that have been treated with hypomethylating agents may be considered if they fulfill one or more of the following criteria: 1) patient has a left ventricular ejection fraction of 45% or less; 2) patient has a serum creatinine of >= 1.4 gm/dl; 3) patient is age 75 or older
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Women must not be pregnant or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration
Participants must agree to use an adequate method of contraception
Must be able to take oral medications
Creatinine clearance >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection
Total serum bilirubin =< 1.5 x upper limit of normal (ULN) unless thought to be due to leukemic involvement
Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 3.0 x ULN unless thought to be due to leukemic involvement

Exclusion Criteria:

Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype)
Active central nervous system involvement with AML
Concurrent active malignancy with expected survival of less than 1 year. 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. All subjects with concurrent malignancies will be reviewed by the principal investigator (PI) prior to enrollment
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
Clinically significant coagulation abnormality, such as disseminated intravascular coagulation
Participants who are currently receiving any other investigational agents
Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (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
Untreated human immunodeficiency virus (HIV) or active hepatitis C detectable by polymerase chain reaction (PCR), or chronic hepatitis B (patients positive for hepatitis B core antibody who are receiving intravenous immunoglobulin [IVIG] are eligible if hepatitis [Hep]B PCR is negative)
Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment
Clinically significant surgery within 2 weeks of enrollment

Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy

Participants with known history of tuberculosis (TB; Mycobacterium tuberculosis) are not eligible for participation. At investigator discretion, latent TB test should be performed for individuals considered to be at high-risk (e.g., immune compromised, persons that have traveled to, or emigrated from, regions with high rates of TB)
Cancer-directed therapy within 1 week prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count
Unwillingness to receive infusion of blood products

Participant on any of the following therapies need to be discussed with 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 not controlled with hydroxyurea)
Patients with known sensitivity to ruxolitinib or venetoclax