RATIONALE: Dasatinib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving dasatinib together with vorinostat may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib when given together with vorinostat in treating patients with accelerated phase or blastic phase chronic myelogenous leukemia or acute lymphoblastic leukemia.
OBJECTIVES: * To define the maximum tolerated dose of dasatinib and vorinostat in patients with accelerated phase or blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. * To assess the toxicity of this regimen in these patients. * To assess, preliminarily, the efficacy of this regimen in these patients. Secondary * To perform correlative studies relevant to this regimen. OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days 1-21 and oral vorinostat twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and blood sample collection periodically for correlative laboratory studies. Samples are assessed by RT-PCR for DNA damage response and proapoptotic elements (GADD45, FANC, and FOXO3A); cytogenetic analysis; flow cytometry; mutation analysis of bcr-abl; and gene expression array analysis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
50 mg orally 2 times per day or 140 mg orally one time per day
100 mg orally 2 times per day
Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL
City of Hope Comprehensive Cancer Center
Duarte, California, United States
City of Hope Medical Group
Pasadena, California, United States
Maximum tolerated dose
Time frame: 21 days after the beginning of treatment
Toxicity as assessed by NCI CTCAE v3.0
Time frame: 21 days from the beginning of the last course of treatment
Response rate
Time frame: One year after treatment completion
Objective tumor response
Time frame: One year after treatment completion
Survival
Time frame: One year after treatment completion
Time to treatment failure
Time frame: One year after treatment completion
Duration of response
Time frame: One year after treatment completion
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Bone marrow aspirate obtained pre-treatment, at first scheduled bone marrow assay and at relapse. Peripheral blood drawn pre-therapy, day +14 of first treatment cycle and at relapse.
Performed at baseline and at every bone marrow analysis on peripheral blood
Peripheral blood drawn prior to starting Vorinostat on Day 1 and on Day 14 of treatment
Performed at the end of cycle two of treatment and every six cycles for patients with accelerated CML and every 3 cycles for patients with blast crisis or Ph+ ALL
Performed pre-treatment and day +14 of treatment