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Trial record 1 of 6 for:    strober stanford
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Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00319657
Recruitment Status : Active, not recruiting
First Posted : April 27, 2006
Last Update Posted : March 25, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Samuel Strober, Stanford University

Tracking Information
First Submitted Date  ICMJE April 28, 2006
First Posted Date  ICMJE April 27, 2006
Last Update Posted Date March 25, 2020
Study Start Date  ICMJE July 2004
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2006)
  • Discontinuation of maintenance immunosuppressive drugs
  • Normal kidney graft function
  • Stable mixed chimerism (all measured for 3 years following kidney transplantation)
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
Official Title  ICMJE Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-Cell Transfusion in HLA-Matched Living Donor Kidney Transplantation
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Combined hematopoietic stem cell and kidney transplantation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Immune Tolerance
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 28, 2006)
15
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00319657
Other Study ID Numbers  ICMJE 367
P01HL075462-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Individual Patient Data will not be shared
Responsible Party Samuel Strober, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Samuel Strober, MD Stanford University
PRS Account Stanford University
Verification Date March 2020

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