Dasatinib and Cyclosporine in Treating Patients With Chronic Myelogenous Leukemia Refractory or Intolerant to Imatinib Mesylate
This phase I trial studies the side effects and the best way to give dasatinib and cyclosporine in treating patients with chronic myelogenous leukemia (CML) refractory or intolerant to imatinib mesylate. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cyclosporine may help dasatinib work better by making cancer cells more sensitive to the drug. Giving dasatinib together with cyclosporine may be an effective treatment for CML
Accelerated Phase Chronic Myelogenous Leukemia
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Chronic Phase Chronic Myelogenous Leukemia
Relapsing Chronic Myelogenous Leukemia
Other: flow cytometry
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Exploiting Synergy in Chronic Myelogenous Leukemia: A Phase Ib Evaluation of Dasatinib Plus Cyclosporine in Patients With Ph+ Leukemia (ESCAPE1b)|
- Safety and tolerability of combining dasatinib and cyclosporine, as assessed by the incidence of adverse events and serious adverse events in this patient population [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]Serious adverse events, toxicity, and patient withdrawals/discontinuations will be determined by the severity, duration, causality, seriousness, and type of event as defined in the protocol.
- Pharmacokinetic profiles of patients taking dasatinib alone versus dasatinib with cyclosporine [ Time Frame: At baseline and on days 7, 21, 49, 77, and 105 ] [ Designated as safety issue: No ]Exposure to dasatinib will be determined and compared using peak levels (Cmax) and areas under the curve (AUC). Paired t-tests will be used to determine statistical significance.
|Study Start Date:||September 2011|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dasatinib and cyclosporine)
Patients receive dasatinib PO QD on days 1-28 and cyclosporine PO BID on days 8-28. Treatment repeats every 28 days for 4 months in the absence of disease progression or unacceptable toxicity.
Other Names:Other: flow cytometry
Correlative studiesOther: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: cyclosporine
I. To define the safety and tolerability of cyclosporine A in combination with dasatinib in adults with Bcr-Abl+ chronic myelogenous leukemia in chronic phase, or when used in specified patients with accelerated phase CML.
I. To assess pharmacokinetic parameters of dasatinib when combined with cyclosporine.
II. To assess whether the combination of dasatinib and cyclosporine alters T cell number and function.
III. To assess the feasibility of determining phosphorylation of Src in peripheral blood mononuclear cells by flow cytometry as a surrogate measure of dasatinib activity.
Patients receive dasatinib orally (PO) once daily (QD) on days 1-28 and cyclosporine PO twice daily (BID) on days 8-28. Treatment repeats every 28 days for 4 months in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood sample collection at baseline and periodically during treatment for pharmacokinetic and pharmacodynamic studies and T-cell number and function by flow cytometry.
After completion of study treatment, patients are followed up for 4 weeks.
|United States, Colorado|
|University of Colorado||Recruiting|
|Denver, Colorado, United States, 80217-3364|
|Contact: Christopher C. Porter 303-724-4665 email@example.com|
|Principal Investigator: Christopher C. Porter|
|Principal Investigator:||Christopher Porter||University of Colorado, Denver|