Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
|Lymphoma Leukemia Multiple Myeloma Myelodysplastic Syndrome||Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant Procedure: T-cell depleted peripheral blood stem cell transplant||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Non-Myeloablative HLA-Matched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies|
- To evaluate the risks of severe (grade III/IV) GVHD or transplant related mortality at < 100 days following HLA-matched non-myeloablative stem cell transplantation (or following "prophylactic" DLI given for chimerism conversion). [ Time Frame: 100 days ]
- To evaluate the incidence of acute and chronic GVHD. [ Time Frame: indefinite ]
- To evaluate the incidence of graft loss. [ Time Frame: 100 days ]
- To evaluate progression free and overall survival. [ Time Frame: indefinite ]
|Study Start Date:||December 2004|
|Study Completion Date:||March 2007|
|Primary Completion Date:||March 2007 (Final data collection date for primary outcome measure)|
T-cell depleted HLA-matched peripheral blood stem cell transplantation
Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7 and 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days-7,-6; fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1.
Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant.
Other Name: Cyclosporine iv beginning on transplant day -1Procedure: T-cell depleted peripheral blood stem cell transplant
Rabbit anti-thymocyte globulin 0.5 mg/kg on transplant day-8, 2.5 mg/kg on day-7, 3.0 mg/kg on day-6; cyclophosphamide 60 mg/kg on days -7, -6; fludarabine 25 mg/m2 on days -5 through -1.
T-cell depleted peripheral blood stem cell transplant .
Other Name: Cyclosporine iv beginning on day -1.
Our prior experience in the lab and in clinical trials with non-myeloablative HLA-matched and mismatched transplant strategies have been remarkable for a low transplant related mortality rate, but a still formidable risk of GVHD and graft rejection. In this trial, we have incorporated a combination ex-vivo T-cell depletion strategy to prevent GVHD with vigorous in vivo depletion of host (and to a lesser extent donor) T-cells to prevent graft rejection.
Patients will receive non-myeloablative conditioning with cyclophosphamide, thymoglobulin, fludarabine, and thymic irradiation, followed by a T-cell depleted PBSC infusion. Cyclosporine will be given for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00113828
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Thomas Spitzer, M.D.||Massachusetts General Hospital, Harvard University|