A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-Center Trial
I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem
cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy)
+/- fludarabine, 90 mg/m^2 and post-grafting immunosuppression with cyclosporine
(CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an
initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.
II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting
following mobilization and high-dose chemotherapy with autografting.
I. To determine the disease free survival and overall survival of non-myeloablative
allografting following autologous PBSCT.
CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive
cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on
days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over
3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3
hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.
TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients
with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine
IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients
with related donors) or 100 (patients with unrelated donors) followed by taper to day 180.
Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related
donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day
96 (patients with unrelated donors).
Some patients may undergo donor lymphocyte infusion if there is evidence of disease
progression and no evidence of graft-vs-host disease (GVHD).
After completion of study treatment, patients are followed up at 1, 1.5, 2, and 3 years and
then annually thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Engraftment of HLA identical PBSC allografts
The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).
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|
|VA Puget Sound Health Care System||Seattle, Washington 98101|