Alemtuzumab (Campath) to Treat T-Large Granular Lymphocyte Leukemia
Condition: T-LGL Lymphoproliferative Disorders
MeSH terms: Lymphoproliferative Disorders
Intervention: Alemtuzumab (Campath)
Intervention description: Alemtuzumab (Campath) will be administered at 10 mg/dose IV for 10 days as an infusion over 2 hours.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Neutropenia; Monoclonal Antibody Therapy; Anti-CD52; T-LGL Leukemia; LGL Leukemia; Leukemia

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        -  Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle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.
    

Eligibility 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.