Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies
The purpose of this study is to determine if recipients of non-myeloablative ex-vivo T-cell depleted peripheral blood (PBSC) stem cell transplantation using a mismatched related donor will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure compared to alternative haploidentical stem cell transplantation.
Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies|
- To evaluate the risk of graft loss and severe GVHD or transplant related mortality at < 100 days following HLA-mismatched non-myeloablative stem cell transplantation. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
- To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2002|
|Estimated Study Completion Date:||December 2007|
|Estimated Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
One major obstacle to further advancement in the role of bone marrow transplant (BMT) in hematological malignancies is graft-versus-host-disease (GVHD), which can best be prevented by removing T-cells from the donor stem cell product. However, previous experience with T-cell depletion has been associated with an increased rate of engraftment failure and leukemic relapse. Another obstacle is that a large fraction of leukemia and lymphomas afflict older patients who are more prone to GVHD and have co-morbid conditions that prevent them from being a candidate for BMT.
This trial uses a non-myeloablative conditioning regimen with cyclophosphamide, MEDI-507, fludarabine, and thymic irradiation followed by a T-cell depleted PBSC infusion. Cyclosporine is used 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.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02116|
|Principal Investigator:||Thomas Spitzer, M.D.||Massachusetts General Hospital, Harvard University|