Rituximab to Treat Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia
This study will test whether the immune-suppressing drug rituximab can increase blood counts and reduce the need for transfusions in patients with moderate aplastic anemia, pure red cell aplasia, or Diamond Blackfan anemia. These are rare and serious blood disorders in which the immune system turns against bone marrow cells, causing the bone marrow to stop producing red blood cells in patients with pure red cell aplasia and Diamond Blackfan anemia, and red blood cells, white blood cells and platelets in patients with aplastic anemia. Rituximab is a laboratory-made monoclonal antibody that recognizes and destroys white blood cells called lymphocytes that are responsible for destroying bone marrow cells in these diseases. The drug is currently approved by the Food and Drug Administration for treating patients with B-cell non-Hodgkin's lymphoma, a disease of white blood cells.
Patients 2 years of age or older with pure red cell aplasia or Diamond Blackfan anemia and patients 18 years of age or older with moderate aplastic anemia who did not respond to previous immunosuppressive therapy or relapsed after treatment may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, electrocardiogram, and bone marrow biopsy (withdrawal of a mall sample of bone marrow through a needle).
Participants receive four doses of rituximab, once a week for 4 weeks through a needle in an arm vein. The infusion rate depends on how well the patient tolerates the drug. The first infusion usually takes 4 to 6 hours and the rest take 3 to 4 hours. The first and fourth infusions are given at NIH; the second and third may be given at NIH or by a patient's referring doctor. Patients who respond to rituximab but then relapse may receive one additional course of four doses. Patients may continue with transfusions and their current medications, including growth factors (e.g., Epogen and Neupogen) while on study, but may have to stop taking immunosuppressive drugs, such as prednisone or cyclosporine. Patients who must start another immunosuppressive medication are taken off rituximab and followed for safety with clinic visits one week and then once a month for 6 months after the first dose of rituximab.
Patients have a blood test once a week while receiving rituximab to evaluate blood counts. After treatment is completed, patients are evaluated once a month until 6 months, then once a year until 3 years to monitor the response to treatment and any drug side effects. Patients are evaluated at NIH for the 3- and 6-month visits and the annual visits. They may be seen at NIH or by their referring doctors for the 1-, 2-, 4- and 5-month visits. A blood test is done at every visit, and a bone marrow aspiration and biopsy are done at the 3-month visit (and when clinically needed to evaluate the effect of rituximab on bone marrow cells).
Red-Cell Aplasia, Pure
Drug: Rituximab (Rituxan)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Recombinant Humanized Anti-CD20 Antibody (Rituximab) in Patients With Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia|
- Primary endpoints will be changed in peripheral blood counts (platelets, absolute neutrophil count, reticulocyte count, hemoglobin) and transfusion requirements at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Secondary endpoints include response at 3 months, durablity of response, disease progression, survival and the response to a second course of therapy when indicated. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Drug: Rituximab (Rituxan)
Many bone marrow failure syndromes in humans result from an immune destruction of single or multiple hematopoietic cell lines. These diseases include aplastic anemia, pure red cell aplasia (PRCA) and Diamond-Blackfan anemia (DBA). Immunosuppression has significantly improved the survival of severe aplastic anemia (SAA) patients. However, the management of moderate aplastic anemia (MAA) remains controversial, given its better prognosis as well as the toxicity and inconvenience of long term immunosuppressants like antithymocyte globulin (ATG) and cyclosporine (CsA). Similarly PRCA and DBA frequently respond to steroids but prolonged or repetitive courses may be needed with significant long term toxicity. There are no studies describing the natural history of MAA in adults. Based on studies in children where 2/3 of patients progress to SAA, we have taken a proactive approach to study activity of milder and less toxic immunosuppressants. During the last several years we introduced daclizumab in the treatment of MAA with a response rate of 38%.
Rituximab (Rituxan(Registered Trademark)) is a chimeric murine/human monoclonal antibody, directed against CD20. CD20 is expressed on pre-B lymphocytes as well as on resting and activated mature B lymphocytes. Rituximab leads to rapid and sustained depletion of both normal and malignant B-cells. Its safety profile is well defined, as it has been given to more than 300,000 patients with non-Hodgkin's lymphoma. Rituximab (Rituxan(Registered Trademark)) has proven beneficial as a therapy for a variety of autoimmune diseases including autoimmune hemolytic anemia, immune thrombocytopenic purpura, PRCA, acquired factor VIII and factor IX inhibitors, chronic refractory graft-versus-host disease, rheumatoid arthritis and systemic lupus erythematosus.
To investigate whether rituximab (Rituxan(Registered Trademark)) has activity in patients with bone marrow failure syndromes, we propose this non-randomized, off label, Phase II study in MAA, PRCA, or DBA. Subjects will be treated with 375 mg/m2 of rituximab (Rituxan(Registered Trademark)), infused intravenously once every week for a total of 4 doses. Patients who respond and relapse may receive a second cycle of drug per PI discretion. Subjects with suboptimal response may receive a second cycle of drug at the 6 month time point.
Subjects will be evaluated for the efficacy and safety of this monoclonal antibody on their disease. Primary endpoints will be changes in peripheral blood counts (platelets, absolute neutrophil count, reticulocyte count, hemoglobin) and transfusion requirements at 6 months. Secondary endpoints include response at 3 months, durability of response, disease progression, survival and the response to a second course of therapy when indicated.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00229619
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|