Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
NCT ID: NCT04797767
Last Updated: 2025-10-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
62 participants
INTERVENTIONAL
2022-02-04
2027-12-31
Brief Summary
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Detailed Description
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This is a dose-escalation study of venetoclax.
Patients will receive induction with granulocyte colony-stimulating factor subcutaneously (SC) on days 0-5 (if peripheral white blood cell count is less than 20,000/uL), cladribine intravenously (IV) on days 1-5, cytarabine IV on days 1-5, and mitoxantrone IV 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.
After completion of study treatment, patients are followed up every 3 months for 12 months.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
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
Interventions
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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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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AbbVie
INDUSTRY
University of Washington
OTHER
Responsible Party
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Principal Investigators
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Mary-Beth M. Percival
Role: PRINCIPAL_INVESTIGATOR
Fred Hutch/University of Washington Cancer Consortium
Locations
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Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Countries
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Central Contacts
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Facility Contacts
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References
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Raychaudhuri S, Gooley TA, Rasmussen A, Quach K, Gill E, Halpern AB, Appelbaum JS, Ghiuzeli CM, Hendrie PC, Cassaday RD, Walter RB, Percival MM. Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm. Blood Neoplasia. 2025 Mar 3;2(3):100085. doi: 10.1016/j.bneo.2025.100085. eCollection 2025 Aug.
Other Identifiers
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NCI-2021-01379
Identifier Type: REGISTRY
Identifier Source: secondary_id
10793
Identifier Type: OTHER
Identifier Source: secondary_id
RG1121403
Identifier Type: -
Identifier Source: org_study_id
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