A Phase 2 interventional study of Busulfan and Cyclophosphamide in Fanconi Anemia, Severe Marrow Failure and Myelodysplastic Syndrome (MDS), sponsored by Children's Hospital Medical Center, Cincinnati. Recruiting at 3 sites in United States. Open to participants aged 3 Months and older. Per ClinicalTrials.gov, last updated 2025-11-12.
Sponsored by Children's Hospital Medical Center, Cincinnati · Phase 2, Interventional, and Treatment
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.
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.
98 studies on the registry are indexed under Fanconi Anemia; 20 are open to participants now.
This study's planned enrollment of 70 is above the median of 20 across 59 interventional studies indexed under Fanconi Anemia.
Browse Fanconi Anemia studies →Children's Hospital Medical Center, Cincinnati is the lead sponsor of 661 studies on the registry; 134 are open to participants now.
Of its 54 completed or terminated interventional studies of FDA-regulated products, 30 (56%) have results posted.
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Patients must have one of the following hematologic diagnoses:
Severe Aplastic Anemia (SAA), with bone marrow cellularity of \<25% OR Severe Isolated Single Lineage Cytopenia and at least one of the following features:
Patients must have adequate physical function measured by:
Exclusion Criteria:
Patients 18 years old or younger with marrow aplasia or single lineage cytopenias will be receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days), as used in our most current study that led to \> 90% survival rates . Busulfan pharmacokinetics will not be used. All patients will receive rabbit ATG (4 doses x 4 days) prior to and granulocyte-colony stimulating factor (G-CSF) after transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells for all patients will be peripheral blood stem cells mobilized by treatment of the donor with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). Enrollment on this arm will include up to 50 patients.
Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: rabbit ATG · Drug: G-CSF · Biological: Peripheral blood stem cell
Patients 18 years old or younger with MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). Busulfan pharmacokinetics will be used in this arm, as the dose of busulfan is higher. All patients will receive rabbit ATG (thymoglobulin) (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for prophylaxis against GVHD. The source of the stem cells for all patients will be peripheral blood stem cells induced and mobilized by treatment of the donor. T-cell will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled in this arm will be 10.
Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: rabbit ATG · Drug: G-CSF · Biological: Peripheral blood stem cell
Patients 19 years old or older with marrow aplasia or MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). In this study, we will test whether outcomes can be improved, yet engraftment maintained, with a slightly reduced dose of busulfan. Patients will receive rabbit ATG (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells will be peripheral blood stem cells collected from donors treated with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled will be 10.
Drug: Busulfan · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: rabbit ATG · Drug: G-CSF · Biological: Peripheral blood stem cell
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.
Also known as: Myleran, Busulfex IV
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.
Also known as: Cytoxan
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.
Also known as: Fludara
Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.
Also known as: thymoglobulin
All patients will also receive G-CSF post-transplant to foster engraftment.
Also known as: Granulocyte colony-stimulating factor, filgrastim, neupogen
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).
Graft Failure or Rejection
Primary non-engraftment is diagnosed when the patient fails to achieve an ANC \>=500/mm3 at any time in the first 28 days post-transplant. If (1) after achievement of an absolute neutrophil count (ANC) \>=500/mm3, the ANC declines to \<500/mm3 for more than 3 consecutive days in the absence of relapse, or, (2) there is absence of donor cells in the marrow and/or blood as demonstrated by chimerism assay in the absence of relapse, a diagnosis of secondary graft failure is made. The patient is not evaluable for graft failure or rejection if recurrence of host MDS is detected concurrently.
Time frame: 5 years
Post-transplant severe morbidity and mortality
The occurrence of severe post-transplant regimen-related severe morbidity (grade IV toxicity) and/or mortality will be the second endpoint of this study. In the context of the agents or agent-combination used for cytoreduction used, particular attention will be given to toxicity involving (1) the liver, (2) the lungs, (3) the oral mucosa and gastrointestinal tract, and (4) the central nervous system.
Time frame: 2 years post-transplant
Graft Versus Host Disease
Patients will be observed for acute and/or chronic graft versus host disease (GvHD). Standard clinical criteria for the grading of acute and chronic GvHD will be done according to IBMTR guidelines.
Time frame: One year
Leukemic Relapse
For patients with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells.
Time frame: 5 years
Secondary malignancies
Patients will be followed for 5 years through annual contact with their treatment center in order to track the risk of developing a secondary malignancy.
Time frame: 5 years
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Children's Hospital Medical Center, Cincinnati