Alemtuzumab (Campath(Registered Trademark)) to Treat T-Large Granular Lymphocyte Leukemia
This study will examine the use of alemtuzumab (Campath(Registered Trademark)) in patients with T cell large granular lymphocytic leukemia (T-LGL). Patients with T-LGL often have reduced white blood cells, red blood cells and platelets, and increased numbers of abnormal cells called large granular lymphocytes (LGLs). Patients may have recurrent infections, anemia, or abnormal bleeding. Campath(Registered Trademark) destroys specific parts of the abnormal LGLs, which interfere with the production of normal blood cells. This study will determine whether Campath(Registered Trademark) can increase blood counts and reduce the number of abnormal LGLs in patients and will examine the side effects of the drug.
Patients 18 to 85 years of age with T-LGL leukemia may be eligible for this study. Participants undergo the following procedures:
Before starting Campath(Registered Trademark) treatment
- Medical history and physical examination, blood tests, electrocardiogram (ECG).
- Echocardiogram (heart ultrasound) and 24-hour Holter monitoring (continuous ECG recording).
- Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone. The procedure is done using local anesthetic.
- Placement of central line, if needed: An intravenous line (tube) is placed into a major vein in the chest. It can stay in the body and be used for the entire treatment period. The line is used to give chemotherapy or other medications, including antibiotics and blood transfusions, and to collect blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room.
- Apheresis: A catheter (plastic tube) is placed in a vein in each arm. Blood is drawn from one vein and run through a cell-separating machine, where the white blood cells are collected and saved. The remaining blood is transfused back to the patients through the vein in the other arm.
During Campath(Registered Trademark) treatment
- Campath(Registered Trademark) therapy: After a small test dose, patients receive10 daily infusions of Campath(Registered Trademark), each of which lasts about 2 hours. The first few infusions are given at the NIH Clinical Center so that the patient can be monitored closely.
- Induction therapy: Aerosolized pentamadine, valacyclovir and other medicines are given to protect against or treat various infections that commonly affect patients with suppressed immune systems.
- Whole blood or platelet transfusions, if needed, and injections of growth factors, if needed.
- Blood tests and check of vital signs (temperature, pulse, blood pressure) every day during treatment. Echocardiogram and 24-hour Holter monitor after the last dose of Campath(Registered Trademark).
Follow-up evaluations after Campath(Registered Trademark) treatment ends
- Blood tests at home or at NIH (weekly for the first 3 months, then every other week until 6 months, then annually for 5 years
- Echocardiogram at NIH (at 3 months only)
- Bone marrow biopsy at NIH (at 6 and 12 months, then as clinically indicated)
- One repeat apheresis collection for laboratory studies.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Alemtuzumab (Campath)|
- The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Secondary endpoints will include relapse-free survival, response at 6 months, life threatening toxicity, reduction in the number of abnormal T-LGL clone, and overall survival. [ Time Frame: Months/years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Drug: 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.
|Contact: Olga J Rios, R.N.||(301) email@example.com|
|Contact: Bogdan Dumitriu, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Bogdan Dumitriu, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|