Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Alemtuzumab (Campath)
18 Years
85 Years
Both
Lymphoproliferative Disorders
Trial Information
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
time point.
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.
Inclusion Criteria
- INCLUSION CRITERIA:
Clinical history supportive of the diagnosis of T-LGL leukemia (i.e. a history of
cytopenias with peripheral blood morphologic evidence of LGLs)
Immunophenotypic studies of peripheral blood showing an increased population of T-LGLs
(suggested by staining with CD3+, CD8+ and CD16+ or CD57+) or gammadelta T cells
Restricted or clonal rearrangement of the T-cell receptor by PCR AND one or more of the
following:
Severe neutropenia (less than 500 neutrophils/microliter); OR
Severe thrombocytopenia (less than 20,000 platelets/microliter), or moderate
thrombocytopenia (less than 50,000 platelets/microliter) with active bleeding; OR
Symptomatic anemia with a hemoglobin less than 9 g/dL or red blood cell transfusion
requirement of greater than 2 units/month for two months prior to initiation of Campath
Ages 18-85 (both inclusive)
EXCLUSION CRITERIA:
A reactive LGL lymphocytosis to a viral infection
Serologic evidence of HIV infection
Infection not adequately responding to appropriate therapy
Previous immunosuppressive therapy with alemtuzumab
History of carcinoma that is not considered cured (excluding non-melanoma skin carcinoma)
Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
or metabolic disease of such severity that it would preclude the subject's ability to
tolerate protocol therapy or that death within 7-10 days is likely
Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if
of childbearing potential
Not able to understand the investigational nature of the study or give informed consent.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s)
Outcome Time Frame:
3 months
Safety Issue:
No
Principal Investigator
Bogdan Dumitriu, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Heart, Lung, and Blood Institute (NHLBI)
Authority:
United States: Federal Government
Study ID:
060190
NCT ID:
NCT00345345
Start Date:
June 2006
Completion Date:
June 2014
Related Keywords:
- Lymphoproliferative Disorders
- Neutropenia
- Monoclonal Antibody Therapy
- Anti-CD52
- T-LGL Leukemia
- LGL Leukemia
- Anemia
- Immunosuppression
- Chronic T Cell Lymphocytosis with Neutropenia
- Leukemia
- Leukemia
- Lymphoproliferative Disorders
- Leukemia, Large Granular Lymphocytic
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
