Hematopoietic Cell Transplantation for Treatment of Patients With Primary Immunodeficiencies and Other Nonmalignant Inherited Disorders Using Low-dose TBI and Fludarabine With or Without Campath
I. Improve donor chimerism levels in patients with inherited nonmalignant disorders
undergoing hematopoietic cell transplantation (HCT) using a reduced intensity conditioning
regimen either through the addition of Campath (alemtuzumab) or a slightly higher dose of
total-body irradiation (TBI).
I. Decrease the incidence and severity of acute and chronic graft-versus-host disease (GVHD)
through use of marrow as the stem cell source and Campath.
II. Assess disease response following HCT.
III. Immune reconstitution following HCT.
IV. Incidence of infections.
V. Overall survival.
VI. Percent of patients with cluster of differentiation (CD)33/CD19 donor chimerism > 50%.
CONDITIONING REGIMEN: *Patients with no life-threatening viral or fungal infections within 1
month before the planned hematopoietic cell transplantation (HCT) receive alemtuzumab
intravenously (IV) over 6 hours on day -10 and fludarabine phosphate IV over 30 minutes on
days -4 to -2. They also undergo low-dose TBI on day 0. Patients with hemophagocytic
lymphohistiocytosis (HLH), immune dysregulation polyendocrinopathy enteropathy X-linked
(IPEX) syndrome, DiGeorge syndrome, or life-threatening viral or fungal infections within 1
month before the planned HCT receive fludarabine phosphate IV over 30 minutes on days -4 to
-2 and undergo 2 low doses of TBI on day 0.
HEMATOPOIETIC CELL TRANSPLANTATION: Patients undergo HCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine IV or orally (PO) 2-3 times daily beginning
on day -3 and continuing until day 100 followed by a taper until day 180. They also receive
mycophenolate mofetil IV or PO 3 times daily beginning on day 0 and continuing until day 40
followed by a taper until day 96.
After completion of HCT, patients are followed up at day 84, at 6, 12, 18 and 24 months
post-transplantation, and then once a year for 3 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients who achieve greater than 50% donor T-cell chimerism
The study will be considered a success and the protocol worthy of further study if there is sufficient evidence that this rate is greater than the 50% rate observed in the most recently transplanted patients with nonmalignant disorders. Analyses will be carried out separately for the alemtuzumab recipients and the TBI recipients. We will be 80% confidence of success if a one-sided 80% confidence interval for the proportion of patients with successful chimerism exceeds 50%. Cumulative incidence will be used to evaluate the probability of chimerism.
At 1 year post transplant
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|Children's Hospital and Research Center at Oakland||Oakland, California 94609-1809|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|Children's Hospital of Wisconsin||Milwaukee, Wisconsin 53201|
|Oregon Health and Science University||Portland, Oregon 97201|