Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Alemtuzumab (Campath)
T Cell Large Granular Lymphocyte (T-LGL) lymphoproliferative disorders are a heterogeneous
group of uncommon diseases which may involve a polyclonal or a monoclonal T cell population,
which bear characteristic surface markers corresponding to activated cytotoxic (CD3+, CD8+)
lymphocytes. They are often associated with quite severe neutropenia, anemia, and
thrombocytopenia, which may be life-threatening. There is some evidence that the abnormal
cytotoxic lymphocyte population may cause the cytopenias by suppressing hematopoiesis,
although the mechanism is unclear. Immunosuppressive therapy has been shown to improve the
cytopenias of T-LGL leukemia, however the long term use of the commonly used agents often
lead to significant toxicity in the older patients which are affected by this disease.
Alemtuzumab (Campath[R]) is currently approved as second line agent in patients with chronic
lymphocytic leukemia (CLL) and has been used successfully in the treatment of certain
autoimmune disorders. In the Hematology Branch, Campath is currently being investigated in
two bone marrow failure syndromes: aplastic anemia and myelodysplasia. Cytopenia(s) is an
important characteristic of patients with T-LGL leukemia, often being the indication for
immunosuppressive therapy. Our preliminary experience with Campath indicates that it is well
tolerated, in particular among the elderly patients.
Therefore, we propose this pilot, Phase II, single agent, study which will evaluate the
efficacy and safety of alemtuzumab (Campath[R]), an immunosuppressive drug, in subjects with
T-LGL leukemia. Commercially available alemtuzumab (Campath[R]) will be administered off
label at 10 mg per day by intravenous infusion for 10 days total. Subjects who do not show a
response to initial Campath or relapse may receive a second cycle of drug after the 3 month
The primary end point of the study is the response rate at three months, defined as
improvement in cytopenia(s). Secondary endpoints will include relapse-free survival,
response at 6 months, life threatening toxicity, reduction in the number of abnormal T-LGL
clone, response to second cycle of Campath, and overall survival.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s)
Bogdan Dumitriu, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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