Combination Therapy of Severe Aplastic Anemia
Condition: Severe Aplastic Anemia
MeSH terms: Anemia; Anemia, Aplastic
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test the safety and effectiveness of a combination of three drugs in treating
      severe aplastic anemia and preventing its recurrence. Two drugs used in this trial ATG and
      cyclosporine are standard combination therapy for aplastic anemia. This study will try to
      improve this therapy in three ways: 1) by altering the drug regimen to allow the drugs to
      work better; 2) by reducing the risk of kidney damage; and 3) by adding a third drug
      mycophenolate mofetil to try to prevent disease relapse.

      Patients with severe aplastic anemia who do not have a suitable bone marrow donor or who
      decline bone marrow transplantation may participate in this study. Patients will have a skin
      test for ATG allergy, chest X-ray, blood test, and bone marrow aspiration before treatment
      begins. ATG will then be started, infused through a vein continuously for 4 days. Ten days
      after ATG is stopped, cyclosporine treatment will begin, taken twice a day by mouth in either
      liquid or capsule form and will continue for 6 months. Also, in the first 2 weeks of
      treatment, patients will be given a full dose of corticosteroid (prednisone) to prevent serum
      sickness that could develop as a side effect of ATG therapy. The dosage will be decreased
      after that. Mycophenolate will be started at the same time as ATG, in two daily doses by
      mouth, and will continue for 18 months.

      Patients will be hospitalized at the beginning of the study. During this time, blood will be
      drawn at 3-week intervals and a bone marrow examination will be repeated 3 months after
      treatment has begun. Additional tests, including X-rays may be required. After hospital
      discharge, patients will be followed on an outpatient basis at 3-month intervals. The
      patients own physician will perform blood tests weekly and kidney and liver function tests
      every 2 weeks during cyclosporine therapy. Transfusions may be required initially.
    

Detailed description: 
      Severe acquired aplastic anemia (SAA) has a poor prognosis if untreated. Bone marrow
      transplantation is available to only a minority of patients due to lack of a matched sibling
      donor, advanced age of the patient, or cost. Clinical studies at NIH and elsewhere have
      demonstrated excellent response rates and improved survival with immunosuppressive
      treatments. Laboratory data implicate underlying cytotoxic T-lymphocyte-mediated suppression
      of hematopoiesis as the likely proximal cause of disease in most patients. In earlier
      clinical protocols we treated SAA with cyclosporine A (CSA) (86-H-0007), antithymocyte
      globulin (ATG) (87-H-0124), and combined ATG and CSA (90-H-0146). While intensive
      immunosuppression is most effective, relapse is common and some patients also develop second
      hematologic complications like myelodysplasia. In this protocol, we modify our regimen by
      delaying the introduction of cyclosporine to promote ATG tolerizing effects and adding
      mycophenolate mofetil (MMF), a new agent that, like ATG may be relatively specific for
      activated lymphocytes, in an effort to reduce the high relapse rate.
    

Intervention name(s): Cyclosporine A; ATG; MMF
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Cyclosporine A; ATG; MMF
Intervention MeSH terms: Cyclosporine; Cyclosporins
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematopoiesis; Bone Marrow Failure; Aplastic Anemia