Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone Marrow Transplantation are enrolling patients into a research study to determine if blood stem cells injected after kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn. Patients must have a healthy, completely human leukocyte antigen (HLA)-matched brother or sister as the organ and stem cell donor.
One to two months before kidney transplant surgery, blood stem cells will be removed from the donor and the cells will be frozen. After transplant surgery, the recipient will receive radiation and anti-T cell antibody treatments for two weeks to prepare for injection of the stem cells. The stem cells will be injected at the end of the two-week treatment. If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation. Patients will be followed in the Stanford clinics for transplant patients. Patients who live outside of the San Francisco Bay Area must remain near Stanford for six weeks after transplant surgery.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-Cell Transfusion in HLA-Matched Living Donor Kidney Transplantation|
- Discontinuation of maintenance immunosuppressive drugs [ Time Frame: Measured at 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||July 2004|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Immune tolerance, kidney transplantation
Induction of immune tolerance in HLA-matched living donor kidney transplantation
Device: Immune tolerance
Kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and antithymocyte globulin followed by immunosuppressive drugs for at least 6 months. Immunosuppressive drugs are stopped at 6 to 12 months if stable mixed chimerism achieved and there is no rejection of the transplant kidney.
The IDE used in this study is the column used for hematopoietic cell sorting.
The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants. Fifteen participants will be conditioned with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (ATG), and given an infusion of donor "mobilized" blood mononuclear cells prior to transplantation.
This is a single-center, open-label study in adult renal transplant patients. Fifteen patients will receive TLI, ATG, and an infusion of CD34+ selected G-CSF mobilized blood cells combined with a fixed number (1x10^6) of CD3+ T cells from the same mobilized blood cell source. Patients will receive a one-month course of mycophenolate mofetil and a six to 12 month tapering course of cyclosporine that will be discontinued at six months. At serial timepoints (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, (3) mixed lymphocyte response (MLR) assays of peripheral blood mononuclear cells against donor and third party cells will be performed, and (4) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue cyclosporine at six months if (1) chimerism is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) there is stable graft function without clinical rejection episodes, and (3) there is lack of histologic rejection on protocol biopsies. In the proposed study, patients will be given a target dose of 8-10x10^6 CD34+ cells/kg and 1x10^6 CD3+ cells/kg because sustained chimerism may be necessary for sustained tolerance to the graft.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00319657
|Contact: Stephan Busque, MDemail@example.com|
|Contact: Asha Shori, CCRPfirstname.lastname@example.org|
|United States, California|
|Stanford University, School of Medicine||Recruiting|
|Stanford, California, United States, 94305|
|Principal Investigator: Samuel Strober, MD|
|Sub-Investigator: Stephan Busque, MD|
|Sub-Investigator: John Scandling, MD|
|Principal Investigator:||Samuel Strober, MD||Stanford University|