Dasatinib and Cyclosporine in Treating Patients With Chronic Myelogenous Leukemia Refractory or Intolerant to Imatinib Mesylate
|Accelerated Phase Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia Relapsing Chronic Myelogenous Leukemia||Drug: dasatinib Other: diagnostic laboratory biomarker analysis Other: pharmacological study Drug: cyclosporine||Phase 1|
|Study Design:||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 ]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 ]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|
|Primary Completion Date:||June 2012 (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: 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01426334
|United States, Colorado|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion|
|Aurora, Colorado, United States, 80045|
|University of Colorado|
|Denver, Colorado, United States, 80217-3364|
|Principal Investigator:||Christopher Porter||University of Colorado Cancer Center - Anschutz Cancer Pavilion|