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

• ClinicalTrials.gov Identifier: NCT01165762
• Recruitment Status: Active, not recruiting
• First Posted: July 20, 2010
• Last Update Posted: July 6, 2022
• Sponsor: Everett Meyer
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Everett Meyer, Stanford University

Tracking Information

• First Submitted Date: July 13, 2010
• First Posted Date: July 20, 2010
• Last Update Posted Date: July 6, 2022
• Actual Study Start Date: July 14, 2010
• Estimated Primary Completion Date: June 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 18, 2018)

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.

• Original Primary Outcome Measures (submitted: July 19, 2010): Long term freedom from transplant immunosuppressive drugs, safety, rate of infection, graft survival and patient survival. [ Time Frame: 5 years and indefinitely if possible ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combined Blood Stem Cell and Kidney Transplant of One Haplotype Match Living Donor Pairs.
• Official Title: Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-cell Transfusion in HLA Haplotype Match Living Donor Kidney Transplantation
• 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match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.
• 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The goal of this study is for the recipients of a living related kidney transplant of one HLA haplotype to be withdrawn of immunosuppressive medication and become "tolerant "to their kidney graft.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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: ESRD

Intervention

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

Study Arms

Experimental: Immune Tolerance, Kidney transplantation

Induction of immune tolerance in Haplotype matched living donor kidney transplantation.

Intervention: Drug: Immune Tolerance

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. No abstract available.
• 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.
• Jensen KP, Hongo DA, Ji X, Zheng P, Pawar R, Wu TH, Busque S, Scandling JD, Shizuru JA, Lowsky R, Shori A, Dutt S, Waters J, Saraswathula A, Baker J, Tamaresis JS, Lavori P, Negrin R, Maecker H, Engleman EG, Meyer E, Strober S. Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients. Blood Adv. 2021 Sep 14;5(17):3290-3302. doi: 10.1182/bloodadvances.2020003669.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 19, 2010): 25
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 14, 2025
• Estimated Primary Completion Date: June 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. All consenting adults who are 18 to 60 years, living donor transplant candidates and have a haplotype related living donor or > 2 HLA antigen matched, unrelated, living donor (including at least one HLA-DR antigen match plus 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 post-transplant.
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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01165762
• Other Study ID Numbers: SU-06232010-6408; P01HL075462 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Everett Meyer, Stanford University
• Original Responsible Party: Stephan Busque, Stanford University School of Medicine
• Current Study Sponsor: Everett Meyer
• Original Study Sponsor: Stanford University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Stephan Busque, MD,MS; Stanford University

• PRS Account: Stanford University
• Verification Date: June 2022