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

June 15, 2021 updated by: Samuel Strober, Stanford University

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with lymphoid irradiation ,will change the immune system such that immunosuppressive drugs can be completely withdrawn.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 If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation.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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants.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

Enrollment (Anticipated)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University, School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Measured at 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: Samuel Strober, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Anticipated)

July 1, 2026

Study Completion (Anticipated)

July 1, 2026

Study Registration Dates

First Submitted

April 28, 2006

First Submitted That Met QC Criteria

April 28, 2006

First Posted (Estimate)

April 27, 2006

Study Record Updates

Last Update Posted (Actual)

June 18, 2021

Last Update Submitted That Met QC Criteria

June 15, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 367
  • P01HL075462-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual Patient Data will not be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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