Dasatinib and Vorinostat in Treating Patients With Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia or Acute Lymphoblastic Leukemia
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.
Genetic: cytogenetic analysis
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: flow cytometry
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||BMS CA180157: A Phase I Combination Study of Dasatinib Plus Vorinostat in Accelerated Phase, Chronic Phase Refractory to Second Line Therapy or Blast Crisis Chronic Myelogenous Leukemia (CML), and in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)|
- Maximum tolerated dose [ Time Frame: 21 days after the beginning of treatment ] [ Designated as safety issue: Yes ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 21 days from the beginning of the last course of treatment ] [ Designated as safety issue: Yes ]
- Response rate [ Time Frame: One year after treatment completion ] [ Designated as safety issue: No ]
- Objective tumor response [ Time Frame: One year after treatment completion ] [ Designated as safety issue: No ]
- Survival [ Time Frame: One year after treatment completion ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: One year after treatment completion ] [ Designated as safety issue: No ]
- Duration of response [ Time Frame: One year after treatment completion ] [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
- 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.
- 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.
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|City of Hope Medical Group|
|Pasadena, California, United States, 91105|
|Principal Investigator:||David Snyder, MD||Beckman Research Institute|