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Recruiting

HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

NCT02143830 · Children's Hospital Medical Center, Cincinnati
In plain English

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Official title
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
About this study
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 criteria
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 refractory or relapsed disease) * Donors will be either human leukocyte antigen (HLA) compatible unrelated or HLA-genotypically matched related donors (no fully matched sibling donor). * Patients and donors may be of either gender or any ethnic background. * Patients must have a Karnofsky adult, or Lansky pediatric performance scale status \> 70%. * Patients must have adequate physical function measured by: 1. Cardiac: asymptomatic or if symptomatic then 1) left ventricular ejection fraction (LVEF) at rest must be \> 50% and must improve with exercise or 2) Shortening Fraction \> 29% 2. Hepatic: \< 5 x upper limit of normal (ULN) alanine transaminase (ALT) and \< 2.0 mg/dl total serum bilirubin. 3. Renal: serum creatinine \<1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 50 ml/min/1.73 m2 4. Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted * Each patient must be willing to participate as a research subject and must sign an informed consent form. * Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study. Exclusion Criteria: * Active CNS leukemia * Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. * Active uncontrolled viral, bacterial or fungal infection * Patient seropositive for HIV-I/II; HTLV -I/II
Study design
Enrollment target: 70 participants
Allocation: non_randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2014-04
Estimated completion: 2028-12
Last updated: 2025-11-12
Interventions
Drug: BusulfanDrug: CyclophosphamideDrug: FludarabineDrug: rabbit ATGDrug: G-CSFBiological: Peripheral blood stem cell
Primary outcomes
  • Graft Failure or Rejection (5 years)
Sponsor
Children's Hospital Medical Center, Cincinnati · other
With: Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center
Contacts & investigators
ContactJamie Wilhelm · contact · Jamie.Wilhelm@cchmc.org · (513)803-1102
ContactSara Loveless, RN · contact · Sara.Loveless@cchmc.org · (513)803-7656
InvestigatorParinda Mehta, MD · principal_investigator, CCHMC
All locations (3)
Memorial Sloan Kettering Cancer CenterCompleted
New York, New York, United States
Cincinnati Children's Hospital Medical CenterRecruiting
Cincinnati, Ohio, United States
Fred Hutchinson Cancer Research CenterRecruiting
Seattle, Washington, United States
HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy · TrialPath