NCT04797767

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

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

OUTLINE: 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

• 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
• Recurrent Myeloid Sarcoma

Interventions

Type	Name	Description
DRUG	Cladribine	Given IV
DRUG	Cytarabine	Given IV
DRUG	Mitoxantrone	Given IV
BIOLOGICAL	Recombinant Granulocyte Colony-Stimulating Factor	Given subcutaneously
DRUG	Venetoclax	Given PO
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection

Timeline

• Start date: 2022-02-04
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2021-03-15
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study