Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
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| ClinicalTrials.gov Identifier: NCT04797767 |
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Recruitment Status :
Recruiting
First Posted : March 15, 2021
Last Update Posted : February 21, 2022
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Sponsor:
University of Washington
Collaborator:
AbbVie
Information provided by (Responsible Party):
University of Washington
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: Cladribine Drug: Cytarabine Drug: Mitoxantrone Biological: Recombinant Granulocyte Colony-Stimulating Factor Drug: Venetoclax | Phase 1 |
OUTLINE:
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 20 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Single-Center Trial Combining Venetoclax With G-CSF, Cladribine, Cytarabine, and Mitoxantrone (CLAG-M) for Patients With AML and High-Grade Myeloid Neoplasms |
| Actual Study Start Date : | February 4, 2022 |
| Estimated Primary Completion Date : | December 31, 2024 |
| Estimated Study Completion Date : | December 31, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial acute myeloid leukemia with mutated CEBPA
Cytogenetically normal acute myeloid leukemia
Core binding factor acute myeloid leukemia
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Cladribine
Given IV
Other Names:
Drug: Cytarabine Given IV
Other Names:
Drug: Mitoxantrone Given IV
Other Names:
Biological: Recombinant Granulocyte Colony-Stimulating Factor Given subcutaneously
Other Names:
Drug: Venetoclax Given PO
Other Names:
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Primary Outcome Measures :
- Incidence of adverse events [ Time Frame: Up to 12 months ]
- Maximum tolerated dose of venetoclax in combination with CLAG-M [ Time Frame: Up to 12 months ]
Secondary Outcome Measures :
- Complete remission rate [ Time Frame: After 2 cycles (each cycle is approximately 35 days) ]
- 1-year survival rate [ Time Frame: At 1 year ]
- Rate of allogeneic hematopoietic cell transplant [ Time Frame: At 1 year ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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)
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Treatment with any of the following within 7 days prior to the first dose of venetoclax
- Steroid therapy for anti-neoplastic intent
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04797767
Contacts
| Contact: Kim Quach | 206.606.8311 | kquach@seattlecca.org | |
| Contact: Mary-Beth M. Percival | 206.606.1320 | mperciva@seattlecca.org |
Locations
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Kim Quach 206-606-8311 kquach@seattlecca.org | |
| Contact: Mary-Beth M. Percival 206-606-1320 mperciva@seattlecca.org | |
| Principal Investigator: Mary-Beth M. Percival | |
Sponsors and Collaborators
University of Washington
AbbVie
Investigators
| Principal Investigator: | Mary-Beth M. Percival | Fred Hutch/University of Washington Cancer Consortium |
| Responsible Party: | University of Washington |
| ClinicalTrials.gov Identifier: | NCT04797767 |
| Other Study ID Numbers: |
RG1121403 NCI-2021-01379 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 10793 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
| First Posted: | March 15, 2021 Key Record Dates |
| Last Update Posted: | February 21, 2022 |
| Last Verified: | December 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Leukemia Neoplasms Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Biphenotypic, Acute Acute Disease Neoplasms by Histologic Type Disease Attributes Pathologic Processes Leukemia, Lymphoid Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine |
2-chloro-3'-deoxyadenosine Venetoclax Mitoxantrone Cladribine Sargramostim Lenograstim Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |