Waldenstrom Macroglobulinemia Clinical Trial
Official title:
A Phase 2 Trial of Daily Alternating Thalidomide and Lenalidomide Plus Rituximab (ThRiL) for Patients With Previously Treated Waldenstrom Macroglobulinemia
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.
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).
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