This phase Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, cytarabine, filgrastim and idarubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with combination chemotherapy may work better in treating patients with acute myeloid leukemia.
Diagnosis of AML by World Health Organization (WHO) criteria. Patients with high risk myelodysplastic syndrome (MDS) as defined by the presence of >= 10% blasts are also eligible at the discretion of the principal investigator
Patients older than 65 who are deemed fit to receive intensive chemotherapy by the treating physician will be eligible after discussion with the principal investigator (PI).
Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
Creatinine clearance >= 30 mL/min based on the Cockcroft-Gault equation
Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
Patients having received any prior BCL2 inhibitor therapy
Subject has known active central nervous system (CNS) involvement with AML
Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram or multi-gated acquisition (MUGA) scan
Single group
Cytarabine
DrugGiven IV
Filgrastim
Biological/VaccineGiven SC
Fludarabine
DrugGiven IV
Idarubicin
DrugGiven IV
Pegfilgrastim
Biological/VaccineGiven SC
Venetoclax
DrugGiven PO
Overall response rate (ORR)
Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.
CR/CRi rate
Will be estimated along with the 95% credible interval.
Hematologic response
Will be estimated along with the 95% credible interval.
Duration of response
Defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.
Morphologic leukemia-free state
Will be estimated along with the 95% credible interval.
Exploratory biomarkers
Will be summarized graphically and with descriptive statistics. Peripheral blood and bone marrow aspirate samples will be obtained at study specified time points. Biomarker assays may include, but are not limited to, BH3 profiling and characterization of BCL-2 and related proteins, and assessment of the depth of response and monitoring of disease recurrence by assessment of minimal residual disease (MRD) in the bone marrow.
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M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
