A Pilot Study of Alemtuzumab (Campath) in Patients With Relapsed or Refractory Severe Aplastic Anemia

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.