HLA-Haploidentical Related Marrow Grafts for the Treatment of Primary Immunodeficiencies and Other Nonmalignant Disorders Using Conditioning With Low-Dose Cyclophosphamide, 200 cGy TBI and Fludarabine; Postgrafting Immunosuppression Will Consist of a Single Low Dose of Cyclophosphamide, MMF and Tacrolimus.
I. To determine safety of nonmyeloablative conditioning and hematopoietic cell
transplantation (HCT) from human leukocyte antigen (HLA)-haploidentical related donors for
patients with nonmalignant inherited disorders who do not have an HLA-matched related or
I. To determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical
related donor graft can establish mixed chimerism (> 5% cluster of differentiation [CD]3+
donor T-cell chimerism) in patients with nonmalignant inherited disorders.
II. To determine the transplant related mortality at day 100.
III. To determine the incidence and severity of graft-versus-host disease (GHVD).
IV. To assess immune reconstitution.
V. To evaluate the infections during the first 200 days after HCT.
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over
1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6 and -5; and undergo
total body irradiation on day -1.
TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on days
3 and 4, and oral mycophenolate mofetil every 8 hours on days 5-35. Patients also receive
tacrolimus IV continuously over 22-24 hours or over 1-2 hours on days 5-180, followed by
oral tacrolimus (when tolerated), with taper on day 84.
After completion of study treatment, patients are followed up at 6, 12, 18 and 24 months,
then annually thereafter for 5 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety as assessed by the probability of transplant-related mortality exceeding 25% or of grades III-IV acute GVHD exceeding 25%
This will be deemed to occur if the lower level of a one-sided 80% confidence interval for either proportion exceeds 25% and will be evaluated after 5 patients have been followed. Adverse events will be assessed using an adapted version of the Common Toxicity Criteria.
By day 100
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
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