A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia (NCT01187017) | Clinical Trial Compass
CompletedPhase 1/2
A Pilot Study of Fludarabine Plus Cyclophosphamide in Refractory Severe Aplastic Anemia
United States1 participantsStarted 2010-08
Plain-language summary
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.
Who can participate
Age range2 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Severe aplastic anemia characterized by:
✓. Failure to respond to an initial course of h-ATG/CsA at least 3 months post-treatment or a suboptimal response to initial h-ATG/CsA defined by both platelet and reticulocyte count \< 50,000 /microL at 3 months post-treatment
✓. Refractory SAA unresponsive to both horse and rabbit ATG-based regimens
✓. Age greater than or equal to 2 years old
✓. Weight greater than or equal to 12 kg
Exclusion criteria
✕. 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)
What they're measuring
1
Response Rate at 6 Months
Timeframe: 6 months
Trial details
NCT IDNCT01187017
SponsorNational Heart, Lung, and Blood Institute (NHLBI)
✕. 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