Alemtuzumab to Treat Severe Aplastic Anemia
Condition: Severe Aplastic Anemia, Refractory; Severe Aplastic Anemia, Relapse
MeSH terms: Anemia; Anemia, Aplastic; Anemia, Refractory
Intervention: Alemtuzumab (Campath ); Cyclosporine
Intervention description: Campath administered at a dose of 10/mg/day for 10 days; Subjects who relapse after initial response to alemtuzumab therapy will have cyclosporine added to the regimen after the 6 month visit. Dosing will be based on ideal body weight and will be adjusted to maintain a target level of 200 - 400 ng /ml.
Intervention MeSH terms: Cyclosporine; Alemtuzumab; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 2 Years
Maximum age: 110 Years
Healthy volunteers: No
Keywords: Immunosuppression; T-cells; Hematopoiesis; Autoimmunity; Thrombocytopenia; Severe Aplastic Anemia; SAA

Summary:

      This study will evaluate the safety and usefulness of a new immunosuppressive drug,
      alemtuzumab (Campath ), in patients with severe aplastic anemia (SAA). SAA is a rare and
      serious blood disorder in which the bone marrow stops making red blood cells, white blood
      cells and platelets. Alemtuzumab is a monoclonal antibody that attaches to and kills white
      blood cells called lymphocytes. In certain types of aplastic anemia, lymphocytes are
      responsible for the destruction of stem cells in the bone marrow, leading to a decrease in
      blood counts. Because alemtuzumab destroys lymphocytes, it may be effective in treating
      aplastic anemia. Alemtuzumab is currently approved to treat chronic lymphocytic leukemia and
      is also helpful in other conditions that require immunosuppression, such as rheumatoid
      arthritis and immune cytopenias.

      Patients 2 years of age and older with severe aplastic anemia whose disease does not respond
      to immunosuppressive therapy or has recurred following immunosuppressive therapy may be
      eligible for this study. Participants undergo the following tests and procedures:

        -  Pretreatment evaluation: Patients have a medical history, physical examination, blood
           tests, electrocardiogram (EKG), echocardiogram, 24-hour Holter monitor (continuous
           24-hour monitoring of electrical activity of the heart), bone marrow biopsy (withdrawal
           through a needle of a small sample of bone marrow for analysis).

        -  Placement of a central line, if needed: An intravenous line (tube) is placed into a
           major vein in the patient's chest. It can stay in the body for the entire treatment
           period and be used to give chemotherapy or other medications, including antibiotics and
           blood transfusions, if needed, and to withdraw blood samples.

        -  Alemtuzumab therapy: Patients are admitted to the NIH Clinical Center for the first few
           injections for close monitoring of side effects. After receiving an initial small test
           dose, patients begin the first of ten daily injections under the skin, each lasting
           about 2 hours. Once patients tolerate the infusions with minimal or no side effects,
           they may be given the remaining infusions on an outpatient basis. Patients who relapse
           after their initial response to alemtuzumab are given cyclosporine to see if this drug
           will boost their immune response.

        -  Patients receive transfusions, growth factors, and antibiotic therapy, as needed.

        -  Infection therapy: Patients are given aerosolized pentamidine to protect against lung
           infections and valacyclovir to protect against herpes infections.

        -  A blood test is done and vital signs are measured every day while patients receive
           alemtuzumab.

        -  Patients have an echocardiogram and 24-hour Holter monitor after the last dose of
           alemtuzumab.

        -  Blood tests are done weekly for the first 3 months after alemtuzumab administration,
           then every other week until 6 months.

      Patients return to the NIH for follow-up visits 1 month, 3 months, 6 months, and yearly for 5
      years after the last dose of alemtuzumab for the following tests and evaluations:

        -  Blood test

        -  Repeat echocardiogram at 3-month visit

        -  Repeat bone marrow biopsy 6 months and 12 months after alemtuzumab, then as clinically
           indicated for 5 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Relapsed severe aplastic anemia after initial hematologic response to a prior course of
        h-ATG or r-ATG based immunosuppression

        Or

        Refractory severe aplastic anemia not responding to both horse-ATG and rabbit ATG-based
        immunosuppression

        The criteria for severe aplastic anemia are two of the three criteria:

          -  Absolute neutrophil count less than or equal to 500 /mm(3)

          -  Platelets to less than or equal to 20,000/mm(3)

          -  Absolute reticulocyte count less than 60,000 /microL

        Age greater than or equal to 2 years old and greater than 12 kg

        Prospective subjects or their parent(s)/responsible guardian(s) must be able to comprehend
        and be willing to sign an informed consent.

        EXCLUSION CRITERIA:

        Known Diagnosis of Fanconi's anemia

        Evidence of a clonal disorder on cytogenetics. In the refractory disease setting,
        prospective subjects with super severe neutropenia (ANC less than 200 /microL) will not be
        excluded if results of cytogenetics are not available or pending.

        Infection not adequately responding to appropriate therapy

        HIV positivity

        Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old
        Man's Beard) within 2 weeks of enrollment

        Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
        or metabolic disease of such severity that it would preclude the patient's ability to
        tolerate protocol therapy, or that death within 7-10 days is likely

        Previous hypersensitivity to alemtuzumab or its components

        Potential subjects with cancer who are on active chemotherapeutic treatment or who take
        drugs with hematological effects will not be eligible

        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