Working… Menu

Induction of Donor Specific Tolerance in Recipients of Live Donor Kidney Allografts by Donor Stem Cell Infusion

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. Identifier: NCT00498160
Recruitment Status : Active, not recruiting
First Posted : July 9, 2007
Last Update Posted : October 8, 2020
Northwestern University
Information provided by (Responsible Party):
Talaris Therapeutics Inc.

Brief Summary:
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with kidney failure allowing a reduction or cessation of immune-suppressive therapy.

Condition or disease Intervention/treatment Phase
Renal Failure Biological: Enriched Hematopoetic Stem Cell Infusion Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Detailed Description:

At the present time, kidney transplant recipients must take anti-rejection medication to prevent rejection of the donated kidney. Even with this medication, chronic rejection is the most common cause of late graft loss. The anti-rejection agents themselves are significantly toxic, with side effects including kidney damage, infection and an increased incidence of cancer. The goal of this study is to allow the patient to develop "tolerance" to the transplanted kidney while maintaining a competent immune system. Tolerance enables the transplant recipient's body to recognize the transplanted organ as self rather than foreign tissue. The recipient will not try to reject the donor kidney and the need for anti-rejection medication could be dramatically decreased or eliminated entirely. To accomplish this, patients in this study will receive specially treated bone marrow taken from their kidney donor. Bone marrow transplant has been shown in animal studies and in humans to induce tolerance following organ transplant.

Two factors limit the application of donor marrow transplant to induce tolerance: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully, a state called mixed chimerism. The toxicity of conditioning and transplantation is significantly reduced.

In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in living donor or deceased donor kidney transplant recipients. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. We believe this study will provide a breakthrough in the approach to kidney transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following kidney transplant and reduce or eliminate the need for anti-rejection therapy.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 1) Induction of Donor Specific Tolerance in Recipients of Kidney Allografts by Donor Bone Marrow Cell Infusion (Deceased Donors) and 2) Induction of Donor Specific Tolerance in Recipients of Live Donor Kidney Allografts by Donor Stem Cell Infusion
Study Start Date : January 2005
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: Living or Deceased Donor Kidney Allograft
Recipients with the need for a living kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same living donor. Recipients with the need for a deceased donor kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same deceased donor
Biological: Enriched Hematopoetic Stem Cell Infusion
Enriched Hematopoetic Stem Cell Infusion

Primary Outcome Measures :
  1. Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment [ Time Frame: one month to three years ]
    Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.

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.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must be between the ages of 18 and 65 years and meet the institution's criteria for renal transplantation for end-organ failure
  • Patient is receiving first renal transplant
  • Patient is receiving a renal transplant only
  • The crossmatch is negative between donor and recipient
  • Women who are of child bearing potential must have a negative pregnancy test (urine test is acceptable) within 48 hours of initiating total body irradiation (TBI) and agree to use reliable contraception for 1 year following transplant

Note: The subjects do not need to be local residents in order to be eligible for this trial, but must be willing to reside in the area, or within a four hour drive, for the first three months of the protocol so that we can monitor them closely in the early post transplant period. As long as there is insurance or funding that will cover the cost of the transplant and any research related complications, it is not necessary for the subjects to be US citizens to participate in this trial.

Exclusion Criteria:

  • Clinically active bacterial, fungal, viral or parasitic infection
  • Pregnancy
  • Clinical or serologic evidence of viral infection which would preclude the recipient from receiving a kidney transplant
  • Previous radiation therapy at a dose which would preclude TBI
  • Positive crossmatch between donor and recipient
  • Evidence for immunologic memory against donor
  • BMI >35 or <18

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 identifier (NCT number): NCT00498160

Layout table for location information
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
Talaris Therapeutics Inc.
Northwestern University
Layout table for investigator information
Study Director: Suzanne T Ildstad, MD Talaris Therapeutics Inc.
Layout table for additonal information
Responsible Party: Talaris Therapeutics Inc. Identifier: NCT00498160    
Other Study ID Numbers: ICT-7392-041698
First Posted: July 9, 2007    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Talaris Therapeutics Inc.:
Kidney transplant
Marrow/stem cell transplant
Additional relevant MeSH terms:
Layout table for MeSH terms
Renal Insufficiency
Kidney Diseases
Urologic Diseases