NCT02928991

Fludarabine Based RIC for Bone Marrow Failure Syndromes

Fludarabine-Based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients With Bone Marrow Failure Syndromes

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 22 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).

Detailed description

Acquired AA patients will receive the experimental regimen of fludarabine with dose-reduced cyclophosphamide, with results in this prospective single arm experimental group evaluated in the context of our institutional historical experience using HD Cy regimens as well as published outcomes using both fludarabine and high-dose cyclophosphamide-based regimens for MRD-BMT in aplastic anemia. iBMF syndrome patients will receive one of two fludarabine-containing regimens based on disease characteristics, and our outcomes will be compared to previously published data using a variety of regimens. Graft versus host disease (GvHD) prophylaxis will consist of cyclosporine/tacrolimus alone for patients with acquired AA or cyclosporine/tacrolimus plus mycophenolate for patients with iBMF syndromes. For both acquired AA and iBMF syndrome patients, donor chimerism will be assessed at scheduled intervals following BMT and will be used to define patients with full donor or mixed chimerism for comparisons of survival, graft failure, cytogenetic, GvHD, and immune reconstitution outcomes.

Conditions

• Bone Marrow Failure Syndromes

Interventions

Type	Name	Description
OTHER	MRD-BMT with Fludarabine-based RIC for Acquired AA	Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3 Cyclophosphamide: Dose: 60mg/kg/day Days: -5, -4 Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2 Bone marrow infusion: Day 0
OTHER	MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia	Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -7, -6, -5, -4, -3 Cyclophosphamide: Dose: 10 mg/kg/day Days: -6, -5, -4, -3 Thymoglobulin: Dose: 3mg/kg/day Days: -4, -3, -2 Bone marrow infusion: Day 0
OTHER	MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia	Fludarabine: Dose: 30mg/m2/day (\<10kg will receive 1mg/kg/day) Days: -6, -5, -4, -3, -2 Busulfan: Dose: every 6 hours for a total of 12 doses with dosing adjustments to achieve a steady state concentration of 900-1200ng/mL OR daily for a total of 3 doses targeting AUC 3600-6000 (micromole/liter)\*minute Days: -7, -6, -5, -4 Thymoglobulin: Dose: 3mg/kg/day Days: -10, -9, -8 Bone marrow infusion: Day 0

Timeline

• Start date: 2015-04-01
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2016-10-10
• Last updated: 2025-05-20

Locations

1 site across 1 country: United States