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Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs

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ClinicalTrials.gov Identifier: NCT00319657
Recruitment Status : Active, not recruiting
First Posted : April 27, 2006
Last Update Posted : May 14, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Samuel Strober, Stanford University

April 28, 2006
April 27, 2006
May 14, 2018
July 2004
July 2021   (Final data collection date for primary outcome measure)
Discontinuation of maintenance immunosuppressive drugs [ Time Frame: Measured at 12 months ]
Study subjects are discontinued from immunosuppressive drugs as they have achieved immune tolerance at 12 months
  • Discontinuation of maintenance immunosuppressive drugs
  • Normal kidney graft function
  • Stable mixed chimerism (all measured for 3 years following kidney transplantation)
Complete list of historical versions of study NCT00319657 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
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with lymphoid irradiation ,will change the immune system such that immunosuppressive drugs can be completely withdrawn.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 If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation.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.

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Intervention Model Description:
Combined hematopoietic stem cell and kidney transplantation
Masking: None (Open Label)
Primary Purpose: Treatment
Immune Tolerance
  • Biological: Hematopoietic cell transplantation
    Transplantation of hematopoietic stem cells from the living donor.
  • Radiation: Total lymphoid irradiation
    Total lymphoid irradiation is used as part of the conditioning regimen for the hematopoietic stem cell transplant.
Experimental: Immune tolerance, kidney transplantation
Intervention: Participants will receive hematopoietic cell transplantation and Total lymphoid irradiation. The intervention is intended to induce immune tolerance in HLA-matched living donor kidney transplantation, to allow withdrawal of the immunosuppressive drugs. Immune tolerance is achieved through the development of donor/recipient mixed chimerism following combined kidney and hematopoietic stem cell transplantation from the living donor.
Interventions:
  • Biological: Hematopoietic cell transplantation
  • Radiation: Total lymphoid irradiation

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
Same as current
July 2021
July 2021   (Final data collection date for primary outcome measure)

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%
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00319657
367
P01HL075462-02 ( U.S. NIH Grant/Contract )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Plan Description: Individual Patient Data will not be shared
Samuel Strober, Stanford University
Stanford University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Samuel Strober, MD Stanford University
Stanford University
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP