A Phase II Study to Evaluate the Efficacy of Posttransplant Cyclophosphamide for Prevention of Chronic Graft-versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation
I. The primary objective of this study is to assess outcomes when high-dose cyclophosphamide
(CY) is administered on days 3 and 4 followed by cyclosporine (CSP) after human leukocyte
antigen (HLA)-matched related or unrelated mobilized blood cell transplantation with
total-body irradiation (TBI) or busulfan (BU)-based conditioning.
I. The secondary objective of this study is to assess hematopoietic cell transplantation
(HCT) outcomes when withdrawal of CSP is accelerated in patients without acute
graft-versus-host disease (GVHD).
OUTLINE: Patients' conditioning regimens are determined by the Clinical Coordinator after
consultation with the attending physician. Based on disease, patients receive either TBI or
fludarabine and busulfan.
PREPARATIVE REGIMEN: Patients receive TBI twice daily (BID) on days -4 or -3 to -1. Some
patients also receive fludarabine intravenously (IV) daily on days -5 to -2 and busulfan IV
over 3 hours once daily (QD) or over 2 hours every 6 hours on days -5 to -2. Patients may
also undergo central nervous system (CNS) prophylaxis, testicular irradiation, and/or
involved field irradiation as per standard practice.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation
(PBSCT) on day 0 per standard practice.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4. Patients
also receive cyclosporine IV every 12 hours or every 8 hours beginning on day 5 with taper
on days 56-126.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at day 180 and then annually
for 5 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Chronic GVHD requiring systemic immunosuppressive treatment
Chronic GVHD will be defined by National Institutes of Health (NIH) criteria and requiring systemic treatment. A reduction in the cumulative incidence of GVHD from ~35% to ~15% at 1 year would represent a reasonable goal. A sample size of 42 patients provides 90% power to observe such a difference with one-side 5% type-1 error.
At 1 year after transplantation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|