Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms

  • End date
    Dec 31, 2024
  • participants needed
  • sponsor
    University of Washington
Updated on 13 May 2022
acute leukemia
ejection fraction
granulocyte colony stimulating factor
gilbert's syndrome
blast cells
colony stimulating factor


This phase I trial finds the best dose and side effects of venetoclax in combination with cladribine, cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (CLAG-M) in treating patients with acute myeloid leukemia and high-grade myeloid neoplasms. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as cladribine, cytarabine, and mitoxantrone, 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 with CLAG-M may kill more cancer cells.



This is a dose-escalation study of 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.

After completion of study treatment, patients are followed up every 3 months for 12 months.

Condition Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, Myeloid Neoplasm, Relapsed Acute Biphenotypic Leukemia, Relapsed Acute Myeloid Leukemia, Relapsed Mixed Phenotype Acute Leukemia, Relapsed Myeloid Neoplasm, Refractory Acute Biphenotypic Leukemia, Refractory Acute Myeloid Leukemia, Refractory Mixed Phenotype Acute Leukemia, Refractory Myeloid Neoplasm
Treatment cytarabine, Mitoxantrone, cladribine, venetoclax, Recombinant Granulocyte Colony-Stimulating Factor
Clinical Study IdentifierNCT04797767
SponsorUniversity of Washington
Last Modified on13 May 2022


Yes No Not Sure

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
Grapefruit or grapefruit products
dose of venetoclax
Seville oranges (including marmalade containing Seville oranges)
Star fruit
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