Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting

Inclusion Criteria:

Patients with AML who are in morphological remission after allogeneic stem cell transplantation with peripheral blood stem cell (PBSC)s or bone marrow if they had at least one of the following disease characteristics:

Therapy related AML
Cytogenetics and molecular features consistent with adverse risk group by European LeukemiaNet classification for AML
Primary induction failure defined as absence of complete remission after two different lines of anti-leukemia therapy following diagnosis
Presence of minimal residual disease by multi-color flow cytometry or cytogenetics or molecular studies at the time of HSCT
Presence of active disease defined as bone marrow blast count > 5% at the time of HSCT
Patients transplanted beyond first remission
Patients with biphenotypic or bilineage leukemia (including a myeloid component) or mixed phenotype acute leukemia (MPAL) or T cell acute lymphoblastic leukemia who are in morphological remission after allogeneic stem cell transplantation with PBSCs or bone marrow
The use of reduced intensity regimen with fludarabine/melphalan (100-140 mg/m^2) with or without total-body irradiation (TBI) with post-transplant Cytoxan
The use of myeloablative regimens including: sequential busulfan (area under curve [AUC] > 5000)/flurabine with post-transplant Cytoxan or TBI/etoposide with any GVHD regimen

Patients who are in remission with no detectable minimal residual disease after allogeneic stem cell transplant should have:

Adequate engraftment within 14 days prior to starting study drug
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L without daily use of myeloid growth factor
Platelet >= 30 x 10^9/L without platelet transfusion within 1 week; and
Be able to start the drug therapy between 42 to 100 days following HSCT
Persistence or reappearance of minimal residual disease by flow cytometry or cytogenetic or molecular testing while being in morphological remission after allogeneic stem cell transplantation
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Serum creatinine =< 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault equation
Serum bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate transaminase (AST) or alanine transaminase (ALT) =< 2.5 x ULN
Alkaline phosphatase =< 2.5 x UL
Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
Negative serum or urine pregnancy test for women with reproductive potential. The only subjects who will be exempt from this criterion are postmenopausal women (defined as women who have been amenorrheic for > 12 months) or subjects who have been surgically sterilized or otherwise proven sterile

Exclusion Criteria:

Active acute GVHD grade II or higher
Active chronic GVHD that is extensive
Uncontrolled GVHD
Concurrent use of systemic immune suppressive other than calcineurin inhibitors, mycophenolate mofetil (MMF) and sirolimus
Active uncontrolled systemic fungal, bacterial or viral infection
Active bleeding
Symptomatic or uncontrolled arrhythmias
Significant active cardiac disease within the previous 6 months, including: New York Heart Association (NYHA) class III or IV congestive heart failure. Unstable angina or angina requiring surgical or medical intervention, and/or myocardial infarction
Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)

Prior history of malignancies, other than leukemia, unless the subject has been free of the disease for >= 1 year. However, subjects with the following history/concurrent conditions are allowed:

Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system)