Alemtuzumab (Campath) to Treat T-Large Granular Lymphocyte Leukemia
Condition: T-LGL Lymphoproliferative Disorders
MeSH terms: Lymphoproliferative Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine the use of alemtuzumab (Campath) 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 destroys specific parts of the abnormal LGLs, which interfere with the
      production of normal blood cells. This study will determine whether Campath 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 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        -  Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle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 treatment

        -  Campath therapy: After a small test dose, patients receive10 daily infusions of Campath,
           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.

      Follow-up evaluations after Campath 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.
    

Detailed description: 
      T Cell Large Granular Lymphocyte (T-LGL) lymphoproliferative disorders are a heterogeneous
      group of uncommon diseases which may involve a monoclonal or oligoclonal 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, 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.
    

Intervention name(s): Alemtuzumab (Campath)
Intervention type(s): Biological
Intervention description(s): Alemtuzumab (Campath) will be administered at 10 mg/dose IV for 10 days as an infusion over 2 hours.
Intervention MeSH terms: Alemtuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neutropenia; Monoclonal Antibody Therapy; Anti-CD52; T-LGL Leukemia; LGL Leukemia; Leukemia