Dose Escalation Study of Revlimid With Fludarabine-Rituximab for CLL/SLL
The purpose of this study is to determine the safety of lenalidomide (revlimid) in combination with fludarabine and rituximab and to determine the highest dose of lenalidomide that can safely be given in that combination. Lenalidomide is a drug that alters the immune system and may also interfere with the the development of tiny blood vessels that help support tumor growth. Lenalidomide is approved by the FDA for the treatment of two different blood cancers called myelodysplastic syndrome and multiple myeloma. Lenalidomide has also been studied in subjects with relapsed CLL. In this research study we are adding lenalidomide to a well-established initial therapy for CLL/SLL.
Chronic Lymphocytic Leukemia
Small Lymphocytic Leukemia
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of Lenalidomide (Revlimid) in Combination With Fludarabine-Rituximab (Rituxan) for Previously Untreated CLL/SLL|
- To evaluate the safety of lenalidomide in combination with fludarabine-rituximab (FR) and to determine the maximum tolerated dose in subjects with previously untreated CLL/SLL. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To determine the objective response rate and progression-free survival following lenalidomide/FR in this patient population [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To determine the improvement in ORR following two months of consolidation lenalidomide after completion of combination therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To assess effects on immune function as measured by cytokine levels, T and NK cell subsets, T cell activation during therapy and DTH vaccine responses. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Study Completion Date:||December 2012|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Experimental: Lenalidomide, fludarabine and rituximab
Lenalidomide-Dose level will depend upon time the participant enrolls on the study: Given orally once a day for 3 weeks followed by a one week rest period fludarabine- Dose level will vary depending upon when participant enters the trial: Given intravenously for 3-5 days Rituximab- Given intravenously on Day 1 of each 28 day cycle
Dose level will depend upon time the participant enrolls on the study: Given orally once a day for 3 weeks followed by a one week rest period
Other Name: RevlimidDrug: Fludarabine
Dose level will vary depending upon when participant enters the trial: Given intravenously for 3-5 daysDrug: Rituximab
Given intravenously on Day 1 of each 28 day cycle
- Participants will be treated in groups (cohorts) of three to six subjects per cohort. The dose of lenalidomide or fludarabine will be increased from one cohort to the next. Regardless of the treatment cohort, participants will receive treatment in cycles lasting 28 days.
- For the first 3-5 days (depending on the group), participants will be treated on an outpatient basis in the infusion room at the Dana-Farber Clinic, with fludarabine and rituximab. Fludarabine is given intravenously for 3-5 days. Rituximab is given intravenously on day 1 of each 28-day cycle. Lenalidomide is given orally once per day for 3 weeks, followed by 1 week of rest.
- Participants will be monitored very closely during the study treatment. During the first 28 day period (cycle 1), a physical exam and routine blood tests will be performed weekly. All participants in a group must finish the first 28-day treatment period before we proceed with the next group. Once started on study treatment, participants will continue for six cycles (a cycle is 28 days) of combination therapy with all three drugs. During that period they will have a physical exam and routine blood tests on day 1 of each treatment cycle, and additional blood tests on day 15 of each cycle.
- When participants complete 6 cycles of combination therapy, they will proceed with two additional months of the lenalidomide alone, for 21 out of 28 days.
- Disease response will be evaluated after 2, 6, and 8 months of study treatment. The following tests and procedures will be performed: Physical exam; blood tests; CT scans to evaluate lymph nodes; skin testing; and bone marrow biopsy if all other tests show no evidence of any remaining CLL and if the baseline bone marrow biopsy was positive
- Participants will have a physical exam and lab work every 3 months as long as their disease remains in remission.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00543114
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Jennifer R. Brown, MD, PhD||Dana-Farber Cancer Institute|