Recruiting
Early Phase 1

Graft Tolerance

Sponsor:

Samuel Strober

Code:

NCT03292445

Conditions

Immune Tolerance

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Immune tolerance after kidney transplant

Donor blood stem cells and T cells

Study Details

Brief summary:

This research study is to determine if donor blood stem cells given after living, related, HLA antigen (Ag) haplotype match or living, unrelated donor kidney transplantation. Minimal HLA antigen matching will include matching of 2 HLA antigens that can be either HLA A, B, and /or DR. This research will change the immune system such that immunosuppressive drugs can be completely withdrawn or reduced to minimal dose without kidney rejection.

Conditions

Immune Tolerance

Study ID

NCT03292445

Start date

Feb 14, 2017

Status verified date

Jul, 2020

Completion date

Feb 14, 2024

Anticipated

Primary completion date

Feb 14, 2022

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. All consenting adults (18 years of age) living donor renal transplant recipients at Stanford University Medical Center who have a one haplotype match donor.
2. Patients who agree to participate in the study and sign an Informed Consent.
3. Patients who have no known contraindication to administration of rabbit ATG or radiation.
4. Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 24 months posttranplant.

Exclusion Criteria:

1. Previous treatment with rabbit ATG or known allergy to rabbit proteins.
2. History of malignancy with the exception of non-melanoma skin malignancies.
3. Pregnant women or nursing mothers.
4. Serological evidence of HIV, Hepatitis B or Hepatitis C infection.
5. Seronegative for Epstein-Barr virus , if donor is seropositive.
6. Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3)
7. Panel Reactive antibody greater then 20% or demonstration of donor specific antibody (DSA).
8. Prior organ transplantation.
9. High risk of primary kidney disease recurrence (i.e. primary FSGS).

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Immune tolerance after kidney transplant

Immune tolerance after kidney transplant will be induced by transfusion of enriched donor blood stem cells and T cells to initiate blood cell mixed chimerism in patients conditioned with total lymphoid irradiation and rabbit anti-thymocyte globulin after kidney transplant. Patients will receive corticosteroids for 14 weeks with gradual dose reduction. They will also receive 12 months of mycophenolate mofetil and 18 months of tacrolimus with dose tapering beginning 9 months post-transplant and continuing as long as mixed chimerism is maintained and there is no evidence of graft versus host disease and no kidney rejection evident. Patients losing chimerism will continue on low dose immunosuppressive drug doses unless additional kidney rejection therapy is needed.

Interventions

Immune tolerance after kidney transplant

Induction of immune tolerance after kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and anti-thymocyte globulin followed by immunosuppressive drugs for 18 months. Immunosuppressive drugs are stopped if stable chimerism is achieved and there is no kidney rejection.

Donor blood stem cells and T cells

Immune tolerance after kidney transplantation resulting from mixed blood cells chimerism will be induced by donor blood stem cells and T cells given to the kidney recipient. Donor cells will be collected by apheresis after "mobilization" of blood stem cells from bone marrow 6-8 weeks before kidney transplant. Collected cells will undergo CD34 selection to recover >10 million donor blood stem cells/kg of patient weight to be combined with up to 150 million donor T cells/kg for transfusion soon after kidney transplant. The IND for this study covers the infusion of donor blood stem cells.

Primary outcome measure

  • Reduction of dependence on immunosuppressive drugs to prevent graft rejection. [ Time Frame: 24 months post-transplant ]

Central Contacts and Locations

Central contacts

Asha Shori, CCRP

6507360245ashas@stanford.edu

Stephan Busque, MD,MS

650-498-6189sbusque@stanford.edu

Locations

Stanford University Medical Center

Recruiting

Palo Alto, California, United States, 94304

Contacts

Asha Shori, CCRP

650-736-0245ashas@stanford.edu

Stephan Busque, MD, MS

650-498-6189sbusque@stanford.edu

Principal Investigator:

John D Sandling, MD

University of Wisconsin

Recruiting

Madison, Wisconsin, United States, 53792-1690

Contacts

Dixon Kaufman, MD

608-265-6471kaufman@surgery.wisc.edu

Tommy Boland

608-263-9459bolandt@suregery.wisc.edu

More Information

Sponsor

Samuel Strober

Last update posted

Jul 17, 2020

Last verified

Jul, 2020

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Samuel Strober on 2020-07-17.