An Early Phase 1 interventional study of MRD-BMT with Fludarabine-based RIC for Acquired AA and MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia in Bone Marrow Failure Syndromes, sponsored by Children's Hospital of Philadelphia. Active, not recruiting at 1 site in United States. Open to participants aged Up to 22 Years. Per ClinicalTrials.gov, last updated 2026-05-28.
Sponsored by Children's Hospital of Philadelphia · Early Phase 1, Interventional, and Treatment
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).
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.
85 studies on the registry are indexed under Bone Marrow Failure Disorders; 33 are open to participants now.
This study's planned enrollment of 25 is close to the median of 24 across 62 interventional studies indexed under Bone Marrow Failure Disorders.
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Of its 28 completed or terminated interventional studies of FDA-regulated products, 22 (79%) have results posted.
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Patients 0-22 years with acquired aplastic anemia or a diagnosed inherited bone marrow failure syndrome, and a fully Human leukocyte antigen (HLA)-matched (10/10) related donor.
Inclusion Criteria:
Patient:
Diseases:
Patients with severe or very severe acquired AA, defined by:
Patients with clinically diagnosed and/or genetically proven iBMF syndromes, resulting in chronic red blood cell or platelet-transfusion dependence and/or an absolute neutrophil count \<500/µL. These disorders include, but are not limited to:
Organ Function:
Donor Selection Criteria:
Exclusion Criteria:
Patients with severe or very severe acquired aplastic anemia (AA). Patients will receive a matched related donor bone marrow transplant following reduced intensity conditioning (RIC) including thymoglobulin (ATG), fludarabine and dose-reduced cyclophosphamide.
Other: MRD-BMT with Fludarabine-based RIC for Acquired AA
Patients with inherited bone marrow failure (iBMF) syndromes with trilineage aplasia includes those with diagnoses of Fanconi Anemia, Dyskeratosis Congenita, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with fludarabine, cyclophosphamide, thymoglobulin.
Other: MRD-BMT with Fludarabine-based RIC for iBMF with trilineage aplasia
Patients with inherited bone marrow failure (iBMF) syndromes without trilineage aplasia includes those with diagnoses of Severe Congenital Neutropenia, Diamond-Blackfan Anemia, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with thymoglobulin, busulfan and fludarabine.
Other: MRD-BMT with Fludarabine-based RIC for iBMF without trilineage aplasia
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
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
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
Rate of graft failure
Combined rate of primary and secondary graft failure. Primary graft failure is defined as no evidence of neutrophil engraftment by day +28 after stem cell infusion. Secondary graft failure is defined as an ANC\<100 for \>7-10 days after initial engraftment occurs and is confirmed by hypocellular bone marrow biopsy and donor engraftment \<20%.
Time frame: Up to 1 year post transplant
Time to neutrophil engraftment
The time from the day of transplant until neutrophil engraftment, which is defined as the first day of ANC \>500/ul for the first of 3 consecutive days.
Time frame: Up to 1 year post transplant
Transplant-related mortality
Time frame: Up to 100 days post transplant
Rate of overall survival
Time frame: Up to 1 year post transplant
Rate of disease free survival
Time frame: Up to 1 year post transplant
Plan to share: No
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Bone Marrow Failure Disorders→
Children's Hospital of Philadelphia