ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : May 14, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Samuel Strober, Stanford University

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with lymphoid irradiation ,will change the immune system such that immunosuppressive drugs can be completely withdrawn.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 If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation.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.


Condition or disease Intervention/treatment Phase
Immune Tolerance Biological: Hematopoietic cell transplantation Radiation: Total lymphoid irradiation Phase 1 Phase 2

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The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants.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 : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Combined hematopoietic stem cell and kidney transplantation
Masking: None (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
Study Start Date : July 2004
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00319657


Locations
United States, California
Stanford University, School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Samuel Strober, MD Stanford University

Additional Information:
Publications of Results:
Other Publications:
Responsible Party: Samuel Strober, Chair of Study, Stanford University
ClinicalTrials.gov Identifier: NCT00319657     History of Changes
Other Study ID Numbers: 367
P01HL075462-02 ( U.S. NIH Grant/Contract )
First Posted: April 27, 2006    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual Patient Data will not be shared

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Samuel Strober, Stanford University:
Kidney Transplantation
Blood Stem Cell Transplantation

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs