A Phase II Trial of HSCT for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
Children's Hospital Medical Center, Cincinnati
Summary
The purpose of this study is to determine whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Patients will undergo a transplant utilizing mis-matched related or matched unrelated donors following a preparative regimen of busulfan, fludarabine, anti-thymocyte globulin and cyclophosphamide.
Description
The trial proposed is a three arm phase II treatment protocol designed to investigate the safety and efficacy of risk-adjusted chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Candidates for this trial will include patients with Fanconi anemia presenting with severe marrow failure (transfusion dependent) or myelodysplastic syndrome, or acute myelogenous leukemia for whom an allogeneic stem cell transplant is indicated.
Eligibility
- Age range
- 0+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have a diagnosis of Fanconi anemia * Patients must have one of the following hematologic diagnoses: 1. Severe Aplastic Anemia (SAA), with bone marrow cellularity of \<25% OR Severe Isolated Single Lineage Cytopenia and at least one of the following features: 1. Platelet count \<20 x 109/L or platelet transfusion dependence\* 2. ANC \<1000 x 109/L 3. Hgb \<8 gm/dl or red cell transfusion dependence\* 2. Myelodysplastic Syndrome (MDS) (based on WHO or IPSS Classification 3. Acute Myelogenous Leukemia (untreated, in remission or with ref…
Interventions
- DrugBusulfan
A standard dose of busulfan, associated with excellent outcomes in our previous trial will be used for young patients with marrow aplasia (arm A). A higher dose of busulfan will be used in younger patients with MDS and AML (arm B) to maximize disease control. A lower dose of busulfan will be used in older patients (arm C) to minimize toxicity.
- DrugCyclophosphamide
Arms A, B and C - Cytoxan will be given as a 1-2 hour infusion for 4 days. The dose will be adjusted according to patients ideal body weight for obese patients.
- DrugFludarabine
Arms A, B and C - Fludarabine will be given IV over 30 minutes daily for 4 days. The dose will be adjusted according to renal function according to Institutional guidelines.
- Drugrabbit ATG
Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.
- DrugG-CSF
All patients will also receive G-CSF post-transplant to foster engraftment.
- Biological
Locations (3)
- Memorial Sloan Kettering Cancer CenterNew York, New York
- Cincinnati Children's Hospital Medical CenterCincinnati, Ohio
- Fred Hutchinson Cancer Research CenterSeattle, Washington