A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
Completed · Phase 1/Phase 2
Conditions studied: Aplastic Anemia, Neutropenia, Pancytopenia, Severe Aplastic Anemia
In brief
Background: * 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. Objectives: \- 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.
Key facts
- Study ID
- NCT01187017
- Run by
- National Heart, Lung, and Blood Institute (NHLBI)
- People needed
- 1
- Starts
- 2010-08-01
- Expected to finish
- 2012-07-01
- Last updated by the study team
- 2021-07-02
Who can join
Age: 2 and older. Sex: any. Healthy volunteers: not accepted.
You may not qualify if…
- Diagnosis of Fanconi anemia
- Cardiac ejection fraction < 30 percent (evaluated by ECHO)
- Evidence of a clonal hematologic bone marrow disorder on cytogenetics. Patients with the presence of trisomy 8, loss of Y or del(20q) will not be excluded in the absence of dysplastic changes in the marrow. Patients with very severe neutropenia (ANC < 200 /microL) will not be excluded initially if cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the patient will go off study)
- Prior immunosuppressive therapy with high dose Cy
- Infection not adequately controlled with appropriate therapy
- Serologic evidence of HIV infection
- Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 30 days is likely
- Subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects
- Current pregnancy or unwillingness to take oral contraceptives or refrain from pregnancy if of childbearing potential
- Not able to understand the investigational nature of the study or to give informed consent
Where it is running
- National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States
Full record on ClinicalTrials.gov
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