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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Northwestern University
Jewish Hospital and St. Mary's Healthcare
Information provided by (Responsible Party):
University of Louisville
ClinicalTrials.gov Identifier:
NCT00498160
First received: July 6, 2007
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Renal Failure
Device: Enriched Hematopoetic Stem Cell Transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment [ Time Frame: one month to three years ] [ Designated as safety issue: No ]
    Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.


Enrollment: 38
Study Start Date: January 2005
Estimated Study Completion Date: December 2024
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enriched Hematopoetic Stem Cell Transplant
Enriched Hematopoetic Stem Cell Transplant
Device: Enriched Hematopoetic Stem Cell Transplant
Bone marrow will be processed via a new technology which will enrich hematopoietic stem cells and graft facilitating cells. Monitoring for chimerism will be done at key time points.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498160

Locations
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Kentucky
Jewish Hospital and Institute for Cellular Therapeutics, University of Louisville
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Northwestern University
Jewish Hospital and St. Mary's Healthcare
Investigators
Principal Investigator: Joseph Leventhal, MD, PhD Northwestern Memorial Hospital
Principal Investigator: Mary Eng, MD Jewish Hospital and St. Mary's Healthcare
  More Information

No publications provided

Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT00498160     History of Changes
Other Study ID Numbers: ICT-7392-041698
Study First Received: July 6, 2007
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Louisville:
Kidney transplant
Tolerance
Marrow/stem cell transplant

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 23, 2014