Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant
This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system.
Bone Marrow Transplantation
Kidney Failure, Chronic
Procedure: Combined kidney and bone marrow transplant
Drug: Cyclosporine A
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Renal Allograft Tolerance Through Mixed Chimerism (ITN010ST)|
- Renal allograft acceptance [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Ability to discontinue immunosuppressive therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Donor-specific tolerance and chimerism [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Immune reconstitution [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Safety profile of the conditioning regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2003|
|Study Completion Date:||July 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
Conditioning regimen consisting of cyclosporine A, rituximab, a short course of corticosteroids, and MEDI-507, followed by bone marrow and kidney transplantation occurring at the same time
T-cell depleting antibodyProcedure: Combined kidney and bone marrow transplant
kidney and bone marrow transplant from same donorDrug: Cyclosporine A
B-cell suppressorDrug: Corticosteroids
Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, patients must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" (a mixing of the donor and recipient's immune system) can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.
Patients in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, patients will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, a man-made antibody known as rituximab to suppress B cells, a short course of steroids, and a T-cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether patients with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.
Patients will be assessed before and after transplantation and will be actively followed for 24 months. Patients will be monitored for graft rejection and medication toxicity. After Month 24, the study will continue with an additional 36 months of medical record-based surveillance.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||David H. Sachs, MD||Department of Medicine, Massachusetts General Hospital|
|Principal Investigator:||A. Benedict Cosimi, MD||Department of Medicine, Massachusetts General Hospital|