Inducing Graft Tolerance in HLA Haplotype Matched Related and 3 Ag Matched Unrelated Living Donor Kidney Transplantation

NCT03292445 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: 40442
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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 This research will change the immune system such that immunosuppressive drugs can be completely withdrawn or reduced to minimal dose without kidney rejection.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

Outcome Measures

Primary Outcomes (1)

• Reduction of dependence on immunosuppressive drugs to prevent graft rejection.

  Percentage of patients able to maintain normal renal function after coming off all immunosuppressive drug therapy and percentage of patients maintaining normal renal function with only minimum effective dose immunosuppressive drug monotherapy.

  24 months post-transplant

Secondary Outcomes (2)

• Incidence of rejection episodes requiring corticosteroid therapy

  24 months post-transplant

• Incidence of graft loss.

  24 months post-transplant

Study Arms (1)

Immune tolerance after kidney transplant

EXPERIMENTAL

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.

Procedure: Immune tolerance after kidney transplant; Drug: Donor blood stem cells and T cells

Interventions

Immune tolerance after kidney transplant PROCEDURE

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.

Immune tolerance after kidney transplant

Donor blood stem cells and T cells DRUG

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.

Also known as: Immune tolerance after kidney transplant

Immune tolerance after kidney transplant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Samuel Strober: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (2)

Stanford University Medical Center

Palo Alto, California, 94304, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792-1690, United States

RECRUITING

Related Publications (4)

• Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.

  PMID: 21991976 BACKGROUND

• Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.

  PMID: 22405058 BACKGROUND

• Scandling JD, Busque S, Shizuru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, Jensen K, Shori A, Strober JA, Lavori P, Turnbull BB, Engleman EG, Strober S. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant. 2015 Mar;15(3):695-704. doi: 10.1111/ajt.13091.

  PMID: 25693475 BACKGROUND

• Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008 Jan 24;358(4):362-8. doi: 10.1056/NEJMoa074191.

  PMID: 18216356 RESULT

Study Officials

• Samuel Md Strober, MD

  Stanford University

  STUDY CHAIR

Central Study Contacts

Asha Shori, CCRP

CONTACT

6507360245; ashas@stanford.edu

Stephan Busque, MD,MS

CONTACT

650-498-6189; sbusque@stanford.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in HLA Haplotype Matched Related and 3 Ag HLA Matched Unrelated Living Donor Kidney Transplantation

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 25, 2017
• Study Start: February 14, 2017
• Primary Completion: February 14, 2022
• Study Completion: February 14, 2024
• Last Updated: July 17, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)