Combining venetoclax with chemotherapy for treating acute myeloid leukemia
A Phase 1/2 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms
This study is testing if combining a drug called venetoclax with a specific chemotherapy can help people with acute myeloid leukemia and high-grade myeloid neoplasms feel better and fight their cancer more effectively.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 62 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Washington Academic / other |
| Drugs / interventions | Chemotherapy |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT04797767 on ClinicalTrials.gov |
What this trial studies
This trial evaluates the effectiveness and safety of venetoclax in combination with a chemotherapy regimen known as CLAG-M for patients with acute myeloid leukemia and high-grade myeloid neoplasms. The study aims to determine the optimal dosage and assess side effects while monitoring how well this combination therapy kills cancer cells. Patients will receive a series of treatments over several cycles, with regular follow-ups to track their progress and any adverse effects. The approach leverages the cancer-fighting properties of venetoclax, which inhibits a protein that helps cancer cells survive, alongside established chemotherapy drugs.
Who should consider this trial
Good fit: Ideal candidates include individuals diagnosed with acute myeloid leukemia or high-grade myeloid neoplasms, particularly those with adverse risk disease or relapsed cases.
Not a fit: Patients with low-risk forms of leukemia or those who do not meet the specific diagnostic criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could improve survival rates and outcomes for patients with aggressive forms of leukemia.
How similar studies have performed: Other studies have shown promise in using venetoclax for treating various hematological malignancies, suggesting potential success for this combination approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Seattle, Washington
- Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Mary-Beth M. Percival — Fred Hutch/University of Washington Cancer Consortium
- Study coordinator: Kim Quach
- Email: kquach@fredhutch.org
- Phone: 206.606.8311
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.