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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:
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:
Full description
Hematopoietic stem cell destruction in many human bone marrow failure syndromes is now recognized to be secondary to immune mechanisms. Severe aplastic anemia (SAA) is a life-threatening blood disease which can be effectively treated with immunosuppressive drug regimens. However, a significant minority of patients with SAA fail to respond to a single course of horse antithymocyte globulin and cyclosporine, and other patients experience relapse, especially on discontinuation of therapy. Pancytopenia secondary to refractory or relapsed aplastic anemia has a poor prognosis, with death usually resulting from infectious complications. Alemtuzumab (Campath ) is a humanized IgG1 monoclonal antibody directed against the CD52 protein; CD52 is expressed on all lymphocytes and monocytes. Alemtuzumab (Campath ) produces profound and persistent lymphopenia. The antibody has been used to treat a wide range of autoimmune diseases, lymphoid malignancies, and in solid organ and hematopoietic stem cell transplantation. In our limited experience with alemtuzumab for the treatment of SAA refractory to horse antithymocyte globulin, meaningful hematologic responses have been observed and toxicity has been modest.
We therefore propose a non-randomized pilot phase II study of this humanized monoclonal antibody in SAA relapsed or refractory to ATG. Commercially available alemtuzumab (Campath ) will be administered at 10 mg per day subcutaneously for 10 days total.
The primary end point of the study is the response rate at 6 months, defined as no longer satisfying blood count criteria for SAA.
Relapse, robustness of the hematopoietic recovery at 3 and 6 months, 3 months responses, survival, and clonal evolution to myelodysplasia and acute leukemia will be secondary end points.
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Inclusion and exclusion 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:
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
Primary purpose
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47 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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