Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia
About this trial
This is an interventional treatment trial for Acute Biphenotypic Leukemia
Eligibility Criteria
Inclusion Criteria:
Acute myeloid leukemia (per the World Health Organization [WHO] 2016 classification) or high-grade myeloid neoplasm (>= 10% myeloid blasts in peripheral blood or marrow)
- Newly diagnosed patients must have adverse risk disease as per the European LeukemiaNet 2017 guidelines
- Relapsed/refractory patients must require first or subsequent salvage therapy
- Patients with biphenotypic or mixed phenotype acute leukemia are eligible
- Age >= 18 years
- Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3.0 X upper limit of normal (ULN)
- Bilirubin =< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Subject must have adequate renal function as demonstrated by a creatinine clearance >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection
- Left ventricular ejection fraction (LVEF) >= 45%, assessed by multigated acquisition (MUGA) or echocardiogram (ECHO) within 3 months prior to study day 0 or after most recent anthracycline administration if appropriate
- Eastern Cooperative Oncology Group (ECOG) =< 2
- Treatment-related mortality (TRM) score < 13.1
- Female subjects of childbearing potential must have negative results for pregnancy test
- Ability to understand and the willingness to sign a written informed consent document
- White blood cell count in peripheral blood must be < 25,000/ul prior to initiation of study therapy (CLAG-M plus venetoclax). Cytoreduction with hydroxyurea and/or cytarabine (e.g., 500 mg/m^2 per dose) is allowed to decrease the risk of tumor lysis syndrome
Exclusion Criteria:
- Acute promyelocytic leukemia or chronic myeloid leukemia in myeloid blast crisis
- Known active central nervous system (CNS) involvement with acute myeloid leukemia (AML)
- Concomitant illness associated with a likely survival of < 1 year
- Active systemic infection, unless disease is under treatment with antimicrobials and considered controlled or stable; patients with fever thought to be likely secondary to leukemia are eligible. Patients with chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment would be excluded. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface [HBs] antigen negative-, anti-HBs antibody positive and anti-hepatitis B core [HBc] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
- Active or clinically significant (or symptomatic) cardiac disease, including active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin within the last 3 months, unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before study day 0
- Known hypersensitivity to any study drug
- Pregnancy or lactation because of the unknown risks of this combination
- Concurrent treatment with any other investigational agent
- Subject is known to be positive for human immunodeficiency virus (HIV)
Treatment with any of the following within 7 days prior to the first dose of venetoclax
- Steroid therapy for anti-neoplastic intent
Administration or consumption of any of the following within 3 days prior to the first dose of venetoclax:
- Grapefruit or grapefruit products
- Seville oranges (including marmalade containing Seville oranges)
- Star fruit
Sites / Locations
- Fred Hutch/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Experimental
Treatment (CLAG-M, venetoclax)
Patients will receive induction with granulocyte colony-stimulating factor on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine on days 1-5, cytarabine on 1-5, and mitoxantrone on days 1-3. Patients also receive venetoclax orally (PO) on days 1-14. Treatment repeats every 28-35 days for up to 2 induction cycles including mitoxantrone, and up to 4 consolidation cycles without mitoxantrone in the absence of disease progression or unacceptable toxicity.