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

• Status: Recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies how well venetoclax and azacitidine work for the treatment of acute myeloid leukemia after stem cell transplantation. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, 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. Giving venetoclax and azacitidine after a stem cell transplant may help control high risk leukemia and prevent it from coming back after the transplant.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Azacitidine; Venetoclax

Criteria

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)