Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant
Summary
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.
Description
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.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Kidney Failure
Intervention
MEDI-507, Combined kidney and bone marrow transplant, Cyclosporine A, Rituximab, Corticosteroids
Location
Massachusetts General Hospital
Boston
Massachusetts
United States
02114
Status
Active, not recruiting
Source
National Institute of Allergy and Infectious Diseases (NIAID)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00063817
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Bone Marrow Neoplasms
Neoplasms located in the bone marrow. They are differentiated from neoplasms composed of bone marrow cells, such as MULTIPLE MYELOMA. Most bone marrow neoplasms are metastatic.
Bone Marrow Purging
Techniques for the removal of subpopulations of cells (usually residual tumor cells) from the bone marrow ex vivo before it is infused. The purging is achieved by a variety of agents including pharmacologic agents, biophysical agents (laser photoirradiation or radioisotopes) and immunologic agents. Bone marrow purging is used in both autologous and allogeneic BONE MARROW TRANSPLANTATION.
Bone Marrow
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
Transplantation Conditioning
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
Bone Marrow Examination
Removal of bone marrow and evaluation of its histologic picture.
Clinical Trials
Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their tr...
Combined Bone Marrow and Kidney Transplant for Multiple Myeloma With Kidney Failure
The purpose of this study is to determine whether a combined bone marrow and kidney transplant will be effective in treating stage II or greater multiple myeloma and associated kidney fail...
The primary objective is to cure multiple myeloma with less toxic allogeneic bone marrow transplantation while inducing renal allograft tolerance through mixed chimerism in patients with e...
Study of MEDI 507 in the Treatment of Pediatric Patients
To assess the safety of escalating dose levels of MEDI-507 in pediatric stem cell and bone marrow allograft recipients who have at least Grade II GvHD.
This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chron...
PubMed Articles
In vivo B-cell depletion with rituximab for alternative donor hemopoietic SCT.
We retrospectively analyzed 55 patients given a fixed dose of rituximab (200 mg) on day+5 after an alternative donor transplant, to prevent EBV DNA-emia; 68 alternative transplants who did not recei...
Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication following allogeneic hematopoietic stem cell transplantation (HSCT). Monitoring...
Belatacept: In Adult Kidney Transplant Recipients.
Belatacept is a second-generation cytotoxic T-lymphocyte-associated antigen-4-Ig fusion protein, which down-regulates T-cell response, and is used in the prophylaxis of organ rejection in adults recei...
BACKGROUND.: Specific tolerance after combined kidney and bone marrow transplantation for multiple myeloma with end-stage renal disease through mixed lymphohematopoietic chimerism has been achieved, a...
Osteoporosis After Transplantation.
Transplantation is an established therapy for end-stage diseases of kidney, lung, liver, and heart among others. Osteoporosis and fragility fractures are serious complications of organ transplantation...
