Rabbit Antithymocyte Globulin Versus Campath-1H for Treating Severe Aplastic Anemia
Condition: Aplastic Anemia
MeSH terms: Anemia; Anemia, Aplastic
Intervention: Campath-1H; r-ATG; CsA
Intervention description: Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).; Rabbit ATG 3.5mg/kg/day for consecutive 5 days; CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.
Intervention MeSH terms: Cyclosporine; Alemtuzumab; Cyclosporins; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Alemtuzumab (Campath-1H); Rabbit ATG; Severe Aplastic Anemia; Cyclosporine; Thrombocytopenia; Leukopenia; Neutropenia; Autoimmunity; Relapse; Anemia

Summary:

      Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is
      effectively treated by immunosuppressive therapy, usually a combination of antithymocyte
      globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent
      to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of
      patients will not show blood count improvement after ATG/CsA. General experience and small
      pilot studies have suggested that such patients may benefit from further immunosuppression.
      Furthermore, analysis of our own clinical data suggest that patients with poor blood count
      responses to a single course of ATG, even when transfusion-independence is achieved, have a
      markedly worse prognosis than patients with robust hematologic improvement. The management of
      such cases is uncertain.

      This study will enroll patients who are either refractory to h-ATG (continued severe
      pancytopenia) or who have only modest improvement in blood counts (weak hematologic
      responders) to receive a further immunosuppressive therapy, delivered either as rabbit ATG
      (Thymoglobulin, r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H
      ). Primary endpoint will be response rate at 3 months defined as no longer meeting criteria
      for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 3 months,
      survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia
      and acute leukemia will be the secondary endpoints.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Severe aplastic anemia confirmed at NIH by:

        Bone marrow cellularity less than 30% (excluding lymphocytes)

        At least two of the following:

        Absolute neutrophil count less than 500/microL;

        Platelet count less than 20,000/ microL;

        Reticulocyte count less than 60,000/ microL.

        Severe aplastic anemia refractory to prior course(s) of h-ATG/CsA defined after 3 months
        from treatment with less or equal to 4 years from receiving h-ATG.

        OR

        Suboptimal response to initial immunosuppression with h-ATG/CsA as defined by platelet and
        reticulocyte count less than 50,000 /microL at 3 months.

        Age greater than or equal to 2 years of age

        EXCLUSION CRITERIA:

        Diagnosis of Fanconi anemia.

        Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia (ANC
        less than 200/microL) will not be excluded initially if results of cytogenetics are not
        available or pending. If evidence of a clonal disorder is later identified, the subject
        will go off study.

        Prior treatment courses with rabbit ATG or high dose cyclophosphamide (200 mg/kg or
        equivalent).

        Infection not adequately responding to appropriate therapy.

        Underlying immunodeficiency state including seropositivity for HIV.

        Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old
        Man's Beard) within two weeks of enrollment.

        Previous hypersensitivity to Campath-1H or its components.

        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.

        Potential subjects with cancer who are on active chemotherapeutic treatment or who take
        drugs with hematological effects will not be eligible.

        Serum creatinine greater than 2.5 mg/dL.

        Current pregnancy or lactation or unwillingness to take contraceptives.

        Inability to understand the investigational nature of the study or give informed consent.