Nonmyeloablative Conditioning With Pre- and Post-Transplant Rituximab Followed by Related or Unrelated Donor Hematopoietic Cell Transplantation for Patients With Advanced Chronic Lymphocytic Leukemia: A Multi-Center Trial
I. Determine whether nonmyeloablative conditioning and allogeneic hematopoietic cell
transplantation (HCT) improves survival at 18 months for patients with fludarabine
(fludarabine phosphate)-refractory, fludarabine/cyclophosphamide/rituximab (FCR)-failed, or
del 17p CLL over that of historical controls (45% at 18 months) given CAMPATH-1H
I. Estimate the overall response rate (complete remission [CR] + partial remission [PR]) by
standard morphologic, flow cytometric, and molecular techniques.
II. Assess the rate of relapse/progression.
III. Define incidences of regimen-related toxicities (RRT) and infections within the first
200 days and the incidence of transplant-related mortality (TRM) within the first year.
IV. Estimate incidences of grade II-III and III-IV acute graft-versus-host disease (GVHD)
and chronic GVHD.
V. Determine whether the addition of Rituximab to the nonmyeloablative conditioning and
allogeneic HCT improves survival at 18 months over our historical data (57% at 18 months).
VI. Determine the incidence of serious adverse events with the addition of Rituximab in
comparison to historical data of unrelated nonmyeloablative HCT.
VII. Evaluate the pharmacokinetics of Rituximab.
VIII. Evaluate B-cell and T-cell immune reconstitution in comparison to historical data of
unrelated nonmyeloablative HCT.
IX. Describe donor and host polymorphisms of the FCgammaRIIIa receptor and cluster of
differentiation (CD)32 and evaluate their impact on disease response and relapse.
X. Investigate the mechanism of disease resistance in relapsed/nonresponding patients.
XI. Isolate donor cytotoxic T lymphocytes specific for host minor histocompatibility
Patients receive a conditioning regimen comprising fludarabine phosphate intravenously (IV)
on days -4 to -2 and rituximab IV on days -3, 10, 24, and 38.
Patients undergo single fraction low-dose total-body irradiation (TBI) on day 0. After
completion of TBI, patients undergo allogeneic hematopoietic stem cell transplantation
(HSCT) on day 0. Patients then receive rituximab IV on days 10, 24, and 38.
Patients receive an immunosuppressive regimen comprising cyclosporine orally (PO) twice
daily (BID) on days -3 to 56 followed by a taper to day 180 (related recipients) or on days
-3 to 100 followed by a taper to day 180 (unrelated recipients). Patients also receive
mycophenolate mofetil PO BID on days 0-27 (related recipients) or three times daily (TID) on
days 0-40 followed by a taper to day 96 (unrelated recipients).
After completion of study treatment, patients are followed up at 6 months, 1 year, and then
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
At 18 months
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Federal Government
|Mayo Clinic||Rochester, Minnesota 55905|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|VA Puget Sound Health Care System||Seattle, Washington 98101|
|Presbyterian - Saint Lukes Medical Center - Health One||Denver, Colorado 80218|