A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
- Severe aplastic anemia (SAA) can lead to problems with bone marrow health and result in low blood cell counts, which require frequent transfusions. Standard initial treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). Patients with SAA who do not respond to initial treatment with ATG (refractory) have a high risk of dying without additional treatment. In these cases, for those who do not have a matched bone marrow transplant donor there is no well-defined standard therapy. In our experience with patients who do not respond to horse ATG + CsA, only about one-third of patients who are re-treated with rabbit ATG + CsA improve. Experience with cyclophosphamide in the treatment of refractory severe aplastic anemia suggests that this drug is able to improve blood counts in about 50% of cases. However, the cyclophosphamide regimen has been associated with a significant infection risk (mostly caused by fungus) in studies conducted over 10 years ago due to the lowering of the white blood cell levels.
- Better antibiotic drugs against fungus have been developed and are widely used to treat patients who have low white blood cell counts and are at risk of developing infections. In SAA patients in particular, these newer antibiotics have had a large impact in preventing and treating fungus infections. Researchers are revisiting the use of cyclophosphamide at lower doses to minimize its side effects given in combination with another immune suppressant, fludarabine.
- To determine the safety and effectiveness of the combination of fludarabine plus cyclophosphamide in treating severe aplastic anemia that has not responded to initial treatments.
- Individuals at least 2 years of age who have severe aplastic anemia that has not improved after treatment with horse ATG or both horse and rabbit ATG.
- After initial screening, medical history, and blood tests, participants will be admitted to the inpatient unit at the National Institutes of Health Clinical Center.
- Participants will receive 2 days of cyclophosphamide, followed by 5 days of fludarabine.
- Participants will also receive antibiotics and other drugs to protect against bacterial, fungal, and viral infections. Participants will take these drugs regularly until their white blood cell counts improve.
- After discharge from the clinical center, participants will have follow-up evaluations at 3 months, 6 months, and annually for 5 years. Evaluations will include blood samples and periodic bone marrow biopsies.
Severe Aplastic Anemia
Refractory Severe Aplastic Anemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia|
- The primary objective is to evaluate the safety and activity profile of Flu/Cy in SAA.-The primary safety endpoint will be toxicity profile in the 6 months following Flu/Cy-The primary efficacy endpoint is response rate at 6 months
- Secondary endpoints will also be evaluated for the study to include: (a) hematologic response at 3 and 12 months and yearly thereafter; (b) relapse (c) clonal evolution to PNH, myelodysplasia or acute leukemia; (e) survival.
|Study Start Date:||August 2010|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Danielle M Townsley, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|