University of Washington
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.
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. Pati…
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 sub…
Given IV
Given IV
Given IV
Given subcutaneously
Given PO
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo blood sample collection