Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are similar diseases of the white blood cells and are typically treated the same way. Recent research shows that a key enzyme in CLL cells is responsible for cell survival. This enzyme is called LYN kinase. Laboratory studies show that inhibition of LYN kinase in CLL cells results in the death of CLL cells. Dasatinib has the ability to inhibit LYN kinase and, therefore, should have some effect on CLL cells. The purpose of this study is to see of the study drug dasatinib, in combination with fludarabine and rituximab, is safe and effective to use for people with relapsed or refractory CLL/SLL.
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Dasatinib With Fludarabine and Rituximab in Relapsed and Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma|
- Response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]To describe the response rate of complete respone and partial response to treatment with this drug combination.
- Duration of Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]To describe the duration of response
- Progression-Free and Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]To describe the progression-free and overall surivial
- Toxicities [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Dasatinib may enhance the myelosuppression expected from fludarabine. This toxicity will be monitored with frequent CBC's. If after Day 21 of a cycle there is a grade 4 cytopenia, a dose reduction will occur in the next cycle of treatment, and that cycle cannot start until the ANC > 1,000 and the platelets > 25,000. There is also a risk for pleural effusions with dasatinib, but the risk will be low, since there is a break from dasatinib dosing on days 15-28 of each cycle. Nevertheless, if a grade 2 pleural effusion occurs, there will be a dose reduction in the next cycle of treatment.
|Study Start Date:||July 2010|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
- Since the purpose of the study is to determine the response rate of the 3 drug regimen, everyone who participates will receive the same dose of the study drug, dasatinib and the 2 standard drugs, fludarabine and rituximab.
- Participants will receive the drugs dasatinib, fludarabine, and rituximab at the following time points through each cycle of treatment. A cycle of study treatment is 28 days. Dasatinib pills will be taken orally each day for the first 2 weeks of each cycle. Fludarabine will be give intravenously on three days of each cycle (Days 3-5 in the first cycle, days 1-3 after that). Rituximab will be given intravenously with a total dose of 375 mg/m2 each cycle (split on Days 3+4 in the first cycle and at the discretion of the treating physician after that on Days 1-3).
- The following procedures will be repeated throughout the study: medical history review; physical exam; performance status test; blood tests and EKG. They will occur daily during the first week of treatment, then weekly for the rest of cycle 1. After cycle 1 these procedures will be done once a week for 4 weeks then once a month for 6 months.
- Tumor assessments will be repeated once every 2 months for the first six months of the study, and then once every 6 months after that.
- Blood samples will be obtained in the first 5 days of treatment for pharmacokinetic studies and pharmacodynamic studies.
- Participants that are benefiting from the study treatment after the first cycle can continue to receive an additional 6 cycles of study treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01173679
|Contact: Philip Amrein, MDfirstname.lastname@example.org|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Sub-Investigator: Jon Arnason, M.D.|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Philip Amrein, MD||Massachusetts General Hospital|