A Phase 2 Trial of Daily Alternating Thalidomide and Lenalidomide Plus Rituximab (ThRiL) for Patients With Previously Treated Waldenstrom Macroglobulinemia
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).
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of patients who demonstrate a response (complete, partial, minor) to treatment
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.
Approximately 24 months
No
Peter Martin, MD
Principal Investigator
Weill Medical College of Cornell University
United States: Food and Drug Administration
1112012086
NCT01779167
June 2012
June 2016
Name | Location |
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Weill Cornell Medical College | New York, New York 10021 |