Cyclophosphamide Plus Cyclosporine in Treatment-Naive 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 treatment for SAA involves injections of antithymocyte globulin (ATG) plus cyclosporine (CsA). This regimen has been shown to improve the blood counts in about two-thirds of patients. However, the ATG/CsA regimen has the following limitations: (a) the disease can come back (relapse) in about one-third of patients who improve initially; and (b) in about 10% to 15% of cases, certain types of bone marrow cancer (such as myelodysplasia and leukemia) can develop (called evolution). Experience with other drugs in SAA such as cyclophosphamide suggests that similar response rates to ATG/CsA can be achieved with a lower risk of relapse and clonal evolution. However, cyclophosphamide was found to have significant side effects in SAA when investigated over 10 years ago due to increase risk of fungal infections.
- 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 in SAA treatment, and plan to give a lower dose of CsA in combination with the immune-suppressing drug cyclophosphamide, as well as antibiotics to protect against infections, as a possible treatment for the disease.
- To determine the safety and effectiveness of the combination of cyclophosphamide and cyclosporine in treating severe aplastic anemia that has not been treated with immunosuppressive therapy.
- Individuals at least 2 years of age who have severe aplastic anemia that has not been treated with immunosuppressive therapy.
- 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 4 days of cyclophosphamide, followed by cyclosporine. Cyclosporine treatment will begin the day after the end of cyclophosphamide treatment and will continue for the following 6 months. The doses will be monitored and adjusted in response to frequent blood tests and monitoring.
- 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
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia|
- The primary objective is to evaluate the safety and activity profile of Cy/CsA in SAA. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Secondary endpoints will also be evaluated for the study to include:(a) Hematological response at 3 and 12 months and yearly thereafter; (b) relapse; (c) clonal evolution to PNH, myelodysplasia or acute leukemia; (d) survival. [ Time Frame: 1 to 5 years ]
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01193283
|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)|