Clinical Trial: Dasatinib and Cyclosporine in Treating Patients With Chronic Myelogenous Leukemia Refractory or Intolerant to Imatinib Mesylate

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Exploiting Synergy in Chronic Myelogenous Leukemia: A Phase Ib Evaluation of Dasatinib Plus Cyclosporine in Patients With Ph+ Leukemia (ESCAPE1b)

Brief Summary: 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.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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.


Original Primary Outcome: Safety and tolerability of combining dasatinib and cyclosporine, as assessed by the incidence of adverse events and serious adverse events in this patient population

Current Secondary Outcome: 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.


Original Secondary Outcome: Pharmacokinetic profiles of dasatinib alone versus dasatinib with cyclosporine

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 30, 2011
Date Started: September 2011
Date Completion:
Last Updated: April 1, 2014
Last Verified: June 2013