Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 5/16/2018 |
| Start Date: | July 2004 |
| End Date: | July 2021 |
Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-Cell Transfusion in HLA-Matched Living Donor Kidney Transplantation
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, in combination with lymphoid irradiation
,will change the immune system such that immunosuppressive drugs can be completely withdrawn.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are withdrawn completely at least six months after transplantation.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.
Marrow Transplantation are enrolling patients into a research study to determine if blood
stem cells injected after kidney transplantation, in combination with lymphoid irradiation
,will change the immune system such that immunosuppressive drugs can be completely withdrawn.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.
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.
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.
Inclusion Criteria:
- Kidney transplant performed at Stanford University Medical Center
- Have an HLA-matched sibling donor
- No known contraindication to administration of rabbit ATG or radiation
- Willing to use a reliable form of contraception for at least 24 months following
transplantation
Exclusion Criteria:
- Previous treatment with rabbit ATG or a known allergy to rabbit proteins
- History of cancer, other than non-melanoma skin cancer
- Pregnant or breastfeeding
- HIV, Hepatitis B, or Hepatitis C infection
- Previous organ transplant
- Leukopenia (white blood cell count less than 3000/mm³)
- Thrombocytopenia (platelet count less than 100,000/mm³)
- cPRA>80%
We found this trial at
1
site
291 Campus Dr
Stanford, California 94305
Stanford, California 94305
(650) 725-3900
Principal Investigator: Samuel Strober, MD
Stanford University School of Medicine Vast in both its physical scale and its impact on...
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