A Study of Dasatinib and Rituximab for Relapsed/Refractory Chronic Lymphocytic Leukemia
- Registration Number
- NCT00949988
- Lead Sponsor
- University of California, San Diego
- Brief Summary
This is an open-label phase I/II study that will investigate the combination of dasatinib and rituximab therapy in patients with relapsed/refractory CLL. In phase I, eligible subjects will take either 100 mg or 140 mg of dasatinib daily along with rituximab on day 1 of each cycle for 6 cycles. In phase II, eligible subjects will all receive the same dose of dasatinib, as established in the phase I portion, along with rituximab on day 1 of each cycle for 6 cycles.
The investigators hypothesize that the combination of dasatinib and rituximab will demonstrate efficacy in the treatment of patients with relapsed/refractory CLL.
- Detailed Description
In phase I, patients will be enrolled in a standard "3+3" dose escalation scheme with two dasatinib cohort doses of 100 mg QD and 140 mg QD x 28 days/cycle with rituximab 500 mg/m2 on day 1 of each cycle (375 mg/m2 on day 1 of cycle 1 only). During the first cycle of each dose cohort patients will receive dasatinib on days -7 to 0 to allow for pharmacokinetic and pharmacodynamic analysis of single agent dasatinib dosing. Cohorts will be assessed for DLTs during the first 2 cycles. Treatment will continue for 6 cycles or until intolerable toxicity or disease progression. It is estimated that accrual of 3-6 patients will be completed in 4-6 months depending on DLTs observed.
The dasatinib dose established in phase I will move forward to the phase II setting. If there are no DLTs, the phase II dose will be chosen based on PD parameters. Dasatinib will be administered for 28 days/cycle with rituximab 500 mg/m2 on day 1 of each cycle (375 mg/m2 on day 1 of cycle 1 only) for 6 cycles or until intolerable toxicity or disease progression. For this portion of the study, up to an additional 22 patients will be enrolled over a 6-month period for a total of 28 patients at the chosen dose level.
For both, phase I and II, patients will complete up to six cycles of D+R therapy and endpoints will be evaluated 8 weeks after treatment. Patients will be followed until disease progression, study withdrawal or death. Patients with a PR or CR will be eligible to remain on dasatinib alone.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dasatinib - 100 mg (Phase I) Dasatinib and Rituximab Dasatinib - 100 mg (Phase I) Dasatinib - 70 mg (Phase I) Dasatinib and Rituximab Dasatinib - 70 mg (Phase I)
- Primary Outcome Measures
Name Time Method Phase I: To Determine the Dose-limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) of D+R Therapy in Patients With Relapsed/Refractory CLL 1 year
- Secondary Outcome Measures
Name Time Method To Determine the Effect of Several Prognostic Factors Including CD38 Expression, ZAP-70 Expression, Immunoglobulin Variable Heavy Chain (VH) Gene Mutation Status and Cytogenetic/FISH Profile on Treatment Response. 2 years A Multi-Center Phase I/II Study of Dasatinib and Rituximab for Relapsed/Refractory Chronic Lymphocytic Leukemia 2 years Phase II:
To determine the efficacy of D+R treatment in patients with relapsed/refractory CLL as measured by complete and partial response ratesTo Assess Duration of Progression-free Survival 5 years To Assess the Safety Profile of D+R in Relapsed/Refractory CLL Patients 2 years To Assess Minimal Residual Disease (MRD) by Flow Cytometry 2 years To Evaluate Pharmacokinetics for Dasatinib in the Treated Patients 2 years To Evaluate in CLL Cells Pharmacodynamic (PD) Parameters Including the Following: in Vivo Signal Transduction Events, Levels of Cellular Apoptosis and Regulation of Apoptosis Related Genes and Proteins. 2 years
Trial Locations
- Locations (1)
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States