Combined Blood Stem Cell and Kidney Transplant of One Haplotype Match Living Donor Pairs.

Study Description

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Brief Summary:

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 donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.

Condition or disease	Intervention/treatment	Phase
ESRD	Drug: Immune Tolerance	Phase 1

Detailed Description:

The goal of this study is for the recipients of a living related kidney transplant of one HLA haplotype to be withdrawn of immunosuppressive medication and become "tolerant "to their kidney graft. The recipient will receive a conditioning regimen composed of low dose radiation to the lymphoid tissue (total lymphoid irradiation, TLI) and anti-thymocyte globulin (ATG) at the time of transplant. They will then be infused with purified "stem cell" and T-cell from their kidney donors 2 weeks after the transplant to try to achieve mixed chimerism of their white blood cells with the donor (the recipient would have a mixture some of the with blood cells of the donor and theirs in their blood). The kidney donor has to provide peripheral stem cell 6-8 weeks before kidney donation. It is an outpatient procedure done using peripheral veins after treatment with G-CSF (filgrastim).Immunosuppressive medication will be decreased gradually and possibly stopped by 1 1/2 year after the transplantation if the recipient meets withdrawing criteria (persistence of mixed chimerism more than 18 months, no episode of rejection and no rejection on surveillance kidney biopsy). Potential candidates need to be approved for kidney transplant and available for close follow-up at Stanford University Medical Center.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	25 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-cell Transfusion in HLA Haplotype Match Living Donor Kidney Transplantation
Study Start Date :	July 2010
Estimated Primary Completion Date :	June 2021
Estimated Study Completion Date :	June 2021

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Immune Tolerance, Kidney transplantation; Induction of immune tolerance in Haplotype matched living donor kidney transplantation.

Drug: Immune Tolerance; Immune tolerance Kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and antithymocyte globulin followed by immunosuppressive drugs for 18 months. Immunosuppressive drugs are stopped if stable chimerism is achieved and there is no rejection of the transplant kidney. The IDE used in this study is the column used for hematopoietic cell sorting.; Other Name: Kidney transplantation

Outcome Measures

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Primary Outcome Measures :

1. Long term freedom from transplant immunosuppressive drugs, safety, rate of infection, graft survival and patient survival. [ Time Frame: 5 years and indefinitely if possible ]
   Subjects on study will have tapering of the immunosuppressive medication and withdrawal of the immunosuppressive medication if withdrawal criteria are met.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. All consenting adults who are 18 to 60 years, living donor transplant candidates and have a happlotype related living donor or > 2 HLA antigen matched, unrelated, living donor (including at least one HLA-DR antigen match pus at least one antigen match of either HLA-A or HLA-B).
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 posttransplant.
5. ABO compatible.

Exclusion Criteria:

1. Previous treatment with rabbit ATG or a 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 than 80% or demonstration of donor specific antibody (DSA).
8. Prior organ transplantation.
9. High risk of primary kidney disease recurrence (e.g atypical HUS). However, patients with primary FSGS will not be excluded.

Contacts and Locations

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Contacts

Contact: Asha Shori, CCRP	(650) 736-0245	ashas@stanford.edu

Locations

United States, California
Stanford University School of Medicine	Recruiting
Stanford, California, United States, 94305
Contact: Asha Shori, CCRP 650-736-0245 ashas@stanford.edu
Principal Investigator: John D Scandling
Sub-Investigator: Judith Anne Shizuru
Sub-Investigator: Dr. Marc L. Melcher
Sub-Investigator: Richard T. Hoppe
Sub-Investigator: Robert Lowsky
Sub-Investigator: Julie M. Yabu
Principal Investigator: Samuel Md Strober
Principal Investigator: Stephan Busque

Sponsors and Collaborators

Stanford University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Stephan Busque	Stanford University

More Information

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Publications:

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.

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.

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.

Responsible Party:	Stephan Busque, Professor of Surgery, Abdominal Transplantation, Stanford University Medical Center, Stanford University
ClinicalTrials.gov Identifier:	NCT01165762 History of Changes
Other Study ID Numbers:	SU-06232010-6408; P01HL075462 ( U.S. NIH Grant/Contract )
First Posted:	July 20, 2010
Last Update Posted:	June 20, 2018
Last Verified:	June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No