Recruiting
Phase 1
Phase 2

Venetoclax & CLAG-M

Sponsor:

University of Washington

Code:

NCT04797767

Conditions

Acute Biphenotypic Leukemia

Acute Myeloid Leukemia

Mixed Phenotype Acute Leukemia

Myeloid Neoplasm

Relapsed Acute Biphenotypic Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cladribine

Cytarabine

Mitoxantrone

Recombinant Granulocyte Colony-Stimulating Factor

Venetoclax

Study Details

Brief summary:

This phase I/II trial finds the best dose, side effects and how well giving 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.

Conditions

Acute Biphenotypic Leukemia

Acute Myeloid Leukemia

Mixed Phenotype Acute Leukemia

Myeloid Neoplasm

Relapsed Acute Biphenotypic Leukemia

Study ID

NCT04797767

Start date

Feb 4, 2022

Status verified date

Apr, 2026

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (per the World Health Organization \[WHO\] 2016 classification) or high-grade myeloid neoplasm (>= 10% myeloid blasts in peripheral blood or marrow as assessed by morphology or multiparameter flow cytometry at initial presentation). Patients with biphenotypic or mixed phenotype acute leukemia are eligible.
  • PHASE I:

  • Newly diagnosed patients presenting for trial entry must have adverse risk disease as per the European LeukemiaNet 2017 guidelines
  • Relapsed/refractory patients presenting for trial entry must require first or subsequent salvage therapy and have detectable blasts in peripheral blood or >= 5% blasts in bone marrow, as assessed by morphology or multiparameter flow cytometry; or extramedullary myeloid sarcoma, per European LeukemiaNet 2017 guidelines.
  • These patients are only allowed in the phase 1 portion of the trial
  • PHASE II: Newly diagnosed patients presenting for trial entry must have adverse risk disease as per the European LeukemiaNet 2022 guidelines
  • 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 and no clinical evidence of congestive heart failure
  • 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. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use an effective method of birth control from the time of signing the consent form until at least 3 months after the last dose of study drug
  • 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
  • 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)
  • Subjects who cannot discontinue concomitant CYP3A inhibitors, except for voriconazole, prior to cycle 1 day 1 (C1D1)
  • 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

Study Design

Enrollment

62 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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. Patients undergo bone marrow biopsy and/or aspiration, and blood sample collection throughout the study.

Interventions

Cladribine

Given IV

Cytarabine

Given IV

Mitoxantrone

Given IV

Recombinant Granulocyte Colony-Stimulating Factor

Given subcutaneously

Venetoclax

Given PO

Bone Marrow Aspiration

Undergo bone marrow aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy

Biospecimen Collection

Undergo blood sample collection

Primary outcome measure

  • Incidence of adverse events (Phase I) [ Time Frame: Up to 12 months ]
  • Maximum tolerated dose of venetoclax in combination with CLAG-M (Phase I) [ Time Frame: Up to 12 months ]
  • Event free survival (Phase II) [ Time Frame: At 6 months ]

Central Contacts and Locations

Central contacts

Kim Quach

206.606.8311kquach@fredhutch.org

Mary-Beth M. Percival

206.606.1320mperciva@fredhutch.org

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

Kim Quach

206-606-8311kquach@fredhutch.org

Mary-Beth M. Percival

206-606-1320mperciva@fredhutch.org

Principal Investigator:

Mary-Beth M. Percival

More Information

Sponsor

University of Washington

Last update posted

Apr 17, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Washington on 2026-04-17.