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.
Severe Aplastic Anemia
|Study Design:||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 Cyclophosphamide and Cyclosporine in Severe Aplastic Anemia (SAA) Patients. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
The objective of this phase I/II study is to assess the safety of cyclophosphamide 120 mg/kg + low dose cyclosporine (100 - 200 micrograms per liter) as initial therapy in subjects with treatment-naïve SAA. We hypothesize that cyclophosphamide/ cyclosporine has activity in SAA with higher complete response rates with few instances of relapse and clonal evolution and could be a viable alternative treatment.
The study will evaluate the safety and activity profile of cyclophosphamide/ cyclosporine in SAA. The safety endpoint will be toxicity profile after 6 months of treatment. The efficacy endpoint is complete response at 6 months.
|Study Start Date:||August 2010|
|Study Completion Date:||September 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: SAA hematologic response
Treatment-naive severe aplastic anemia patients will receive a low dose of cyclophosphamide (120mg/kg) and low dose cyclosporine ( target therapeutic level of 100-200 micrograms per liter). Cyclophosphamide will be given once daily for 4 doses. Cyclosporine will be started after cyclophosphamide completion, cyclosporine will be given twice daily. The dosing will be modified to attain the therapeutic level.
30 my/kg for 4 days
Other Name: CytoxanDrug: Cyclosporine
daily to a trough of 100 t0 200 ng/ml
Show Detailed Description
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)|