This phase II trial studies how well cladribine, idarubicin, cytarabine, and venetoclax work in patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. Drugs used in chemotherapy, such as cladribine, idarubicin, and cytarabine, 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. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving cladribine, idarubicin, cytarabine, and venetoclax may help control the disease in patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia.
Additional locations may be listed on ClinicalTrials.gov for NCT02115295.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Tapan M. Kadia
Phone: 713-792-7305
PRIMARY OBJECTIVE:
I. To determine the complete response rate (CR) of cladribine in combination with idarubicin and cytarabine (araC) in patients with acute myeloid leukemia (AML), high risk (HR) myelodysplastic syndrome (MDS), or myeloid blast phase of chronic myeloid leukemia (CML).
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR) of cladribine in combination with idarubicin and araC in patients with AML, HR MDS, or myeloid blast phase of CML.
II. To assess overall survival (OS) and event free survival (EFS) of patients treated with cladribine, idarubicin, and araC.
III. To assess the duration of response to the combination in patients with AML, HR MDS, or myeloid blast phase of CML.
IV. To determine the safety and tolerability of the combination in patients with AML, HR MDS, or myeloid blast phase of CML.
EXPLORATORY OBJECTIVES:
I. To study and describe the relationship between pretreatment patient/disease characteristics (including AML-associated molecular abnormalities) and outcome.
II. To identify molecular biomarkers predictive of response to therapy.
III. To study and describe the relationship between patient/disease characteristics, use of intrathecal prophylaxis, and incidence of leptomeningeal disease.
IV. To study the trajectories of leukemia mutations and molecular minimal residual disease (MRD) during the therapy.
V. To characterize MRD and evaluate its impact on relapse and outcome in patients with AML with or without allogeneic stem cell transplantation.
VI. To characterize the pharmacokinetics (PK) of cladribine in patients with AML after intravenous (IV) administration of 5 mg/m^2 once-daily for 5 days.
OUTLINE:
INDUCTION: Patients receive cladribine intravenously (IV) over 1-2 hours and cytarabine IV over 2 hours on days 1-5 and idarubicin IV over 30-60 minutes on days 1-3. Patients with untreated AML and MDS receive venetoclax orally (PO) daily on days 2-8. AML patients with known FLT3-ITD and FLT3 kinase domain mutations may receive sorafenib PO twice daily (BID) on days 1-14, midostaurin PO BID on days 6-19, or gilteritinib PO once daily (QD) on days 1-14.
CONSOLIDATION: Patients receive cladribine IV over 1-2 hours and cytarabine IV over 2 hours on days 1-3 and idarubicin IV over 30-60 minutes on days 1-2. Patients with untreated AML and MDS receive venetoclax PO daily on days 2-8. AML patients with known FLT3-ITD and FLT3 kinase domain mutations may receive sorafenib PO BID on days 1-28 starting in cycle 2, midostaurin PO BID on days 6-19, or gilteritinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration or biopsy and blood sample collection while on study.
After completion of study treatment, patients are followed up every 6-12 months.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorTapan M. Kadia
