Thalidomide, Lenalidomide, and Rituximab for Previously Treated Waldenstrom Macroglobulinemia (THRiL for WM)
The purpose of this study is to evaluate the efficacy and safety of daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated Waldenstrom macroglobulunemia (WM). Thalidomide and lenalidomide are drugs that modulate the immune system and have been shown to bring about responses in subjects with WM. However, their use has been limited due to side effects. The investigators hypothesize that alternating doses of thalidomide and lenalidomide may alleviate the side effects while preserving the effectiveness of the therapies.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Trial of Daily Alternating Thalidomide and Lenalidomide Plus Rituximab (ThRiL) for Patients With Previously Treated Waldenstrom Macroglobulinemia|
- Number of patients who demonstrate a response (complete, partial, minor) to treatment [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]
Response criteria for subjects with WM is based upon the Consensus Panel Recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.
Overall response rate (CR + PR + MR) measured at time of best response.
- Number of adverse events experienced with alternating thalidomide and lenalidomide plus rituximab for subjects with previously treated Waldenstrom's Macroglobulinemia [ Time Frame: approximately 24 months per patient ] [ Designated as safety issue: Yes ]Capture the number of adverse events experienced when combining thalidomide, lenalidomide, and rituximab in patients with previously treated WM
- Survival of subjects treated with THRiL for WM. [ Time Frame: approximately 24 months per patient ] [ Designated as safety issue: No ]Estimate overall survival of patients enrolled on THRiL for WM.
- Rate of rituximab related IgM flare [ Time Frame: Approximately 24 months per patient ] [ Designated as safety issue: Yes ]Estimate the rate of rituximab-related IgM flare
- Time to response [ Time Frame: approximately 24 months ] [ Designated as safety issue: No ]Measure the time from initiating therapy to demonstrating response in WM.
- Response duration of subjects treated with THRiL for WM [ Time Frame: 24 months ] [ Designated as safety issue: No ]Measure response duration of patients enrolled on THRiL for WM
|Study Start Date:||June 2012|
|Study Completion Date:||April 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: All Patients
Daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in patients with previously treated WM
Thalidomide 50 mg (every ODD day of a 28 day cycle: Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 & 27)Drug: Lenalidomide
Lenalidomide (every EVEN day of a 28 day cycle: Days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 & 28). Lenalidomide will be initiated at a starting dose of 5 mg.
Other Name: RevlimidDrug: Rituximab
Rituximab 375 mg/m2 IV on Days 1, 8, 15 and 22 (+/- 2 days) and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycle 7, 13, 19, etc).
Other Name: Rituxan
Waldenstrom macroglobulinemia (WM) is an incurable B-cell lymphoproliferative disorder characterized by expansion of malignant B-lymphocytes and excessive production of monoclonal IgM. The survival and proliferation of the neoplastic WM cells is highly dependent on signals from the microenvironment. Thalidomide and lenalidomide are immunomodulatory agents with single agent activity in WM. Their use is limited by significant toxicities, including tumor flare (thalidomide and lenalidomide); sedation, constipation, and neuropathy (thalidomide); and cytopenias (lenalidomide). Alternating doses of thalidomide and lenalidomide may alleviate the toxicities, while preserving efficacy since the agents have non-overlapping toxicities and yet similar hypothesized mechanisms of action. Additionally, starting at a lower dose of lenalidomide than previously studied in WM may allow for improved tolerability. A pilot study of daily alternating therapy in subjects with chronic lymphocytic leukemia demonstrated that the two agents could be combined with non-overlapping toxicity. This phase II study aims to evaluate the efficacy and safety of daily alternating thalidomide and lenalidomide plus rituximab (ThRiL) in subjects with previously treated WM.
Subjects will receive thalidomide 50 mg every other day (i.e., every odd day: days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 & 27 of a 28 day cycle) alternating with lenalidomide on every other day (i.e., every even day: days 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 & 28 of a 28 day cycle), dosed based upon stepwise incremental dosing. Rituximab 375 mg/m2 will be administered on days 1, 8, 15 and 22 starting with Cycle 1 and then again on the same weekly x 4 schedule every 6th cycle thereafter (Cycles 7, 13, 19, etc).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01779167
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|Principal Investigator:||Peter Martin, MD||Weill Medical College of Cornell University|