NCT02143830

HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Children's Hospital Medical Center, Cincinnati · Academic / Other
• Sex: All
• Age: 3 Months
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Fanconi Anemia
• Severe Marrow Failure
• Myelodysplastic Syndrome (MDS)
• Acute Myelogenous Leukemia (AML)

Interventions

Type	Name	Description
DRUG	Busulfan	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.
DRUG	Cyclophosphamide	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.
DRUG	Fludarabine	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.
DRUG	rabbit ATG	Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.
DRUG	G-CSF	All patients will also receive G-CSF post-transplant to foster engraftment.
BIOLOGICAL	Peripheral blood stem cell	The source of stem cells for all patients will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 4-6 days. T-cell depletion will be uniformly performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device).

Timeline

• Start date: 2014-04-01
• Primary completion: 2026-12-01
• Completion: 2028-12-01
• First posted: 2014-05-21
• Last updated: 2025-11-12

Locations

3 sites across 1 country: United States