TLI, TBI, ATG & Hematopoietic Stem Cell Transplantation and Recipient T Regs Therapy in Living Donor Kidney Transplantation

NCT03943238 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 50540
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This study will determine whether a preparatory regimen including total lymphoid irradiation (TLI), total body irradiation (TBI), anti-thymocyte globulin (ATG) and infusion of the donor hematopoietic stem cells when given along with recipient regulatory T cells (Tregs) will allow for eventual discontinuation of anti-rejection drugs after living donor kidney transplantation.

Conditions

Living Donor Kidney Transplantation

Keywords

kidney transplant; Immunological Tolerance; Tregs; Stem cells

Outcome Measures

Primary Outcomes (2)

• Count of participants with sustained mixed chimerism of >25% at 18 months

  Chimerism is defined as the co-existence of the immune cell from both the donor and the recipient.

  Month 18

• Count of participants able to withdraw from immunosuppressive drugs without evidence of rejection at 18 months

  Month 18

Secondary Outcomes (2)

• Count of participants with adverse events associated with the infusion of the Tregs cell product

  up to 2 years

• Count of participants with bacterial, viral, or fungal infections

  up to 2 years

Study Arms (1)

Combined kidney/stem cell transplants and recipient's Tregs

EXPERIMENTAL

Preparatory regimen including TLI, TBI, ATG after kidney transplantation followed by infusion of donor CD34+, T cell and recipient Tregs

Biological: Infusion of Donor Hematopoetic Stem Cells and Recipient Tregs

Interventions

Infusion of Donor Hematopoetic Stem Cells and Recipient Tregs BIOLOGICAL

Living donor kidney transplant recipients will receive after a preparatory regimen of total lymphoid irradiation, total body irradiation and anti-thymocyte globulin an infusion of purified donor CD34+ of \>10 x10\^6 cells /Kg, 100 x 10\^6 donor T cell/ Kg and and an escalated dose of recipient Tregs starting at 25 x10\^6/Kg.

Combined kidney/stem cell transplants and recipient's Tregs

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 who are 18 to 65 years, living donor renal transplant recipients at Stanford University Medical Center or Northwestern Medicine who have a haplotype matched (minimum single Human Leukocyte Antigen - DR locus (HLA-DR) and HLA-A or B match) living related or unrelated 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 1 year posttransplant

You may not qualify if:

• Previous treatment with rabbit ATG or a 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 surface antigen positive (HBsAg+), or Hepatitis C infection. Epstein Barr Virus (EBV) positive to EBV negative.
• Leukopenia (with a white blood cell count \< 3000/mm3) or thrombocytopenia (with a platelet count \< 100,000/mm3).
• Panel Reactive Antibody (PRA) greater than 80% or demonstration of historic and/or current donor specific antibody (DSA)
• Prior organ transplantation
• High risk of primary kidney disease recurrence
• Advanced coronary or vascular disease.

Sponsors & Collaborators

• Stanford University: lead
• California Institute for Regenerative Medicine (CIRM): collaborator
• Northwestern University: collaborator

Study Sites (2)

Stanford University

Palo Alto, California, 94305, United States

RECRUITING

Nothwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (5)

• Leventhal JR, Ildstad ST. Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell Infusion: The importance of durable chimerism. Hum Immunol. 2018 May;79(5):272-276. doi: 10.1016/j.humimm.2018.01.007. Epub 2018 Mar 2.

  PMID: 29409743 BACKGROUND

• Ildstad ST, Leventhal J, Wen Y, Yolcu E. Facilitating cells: Translation of hematopoietic chimerism to achieve clinical tolerance. Chimerism. 2015 Apr 3;6(1-2):33-9. doi: 10.1080/19381956.2015.1130780. Epub 2016 Jan 8.

  PMID: 26745761 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, 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, Lowsky R, Shizuru J, Shori A, Engleman E, Jensen K, Strober S. Macrochimerism and clinical transplant tolerance. Hum Immunol. 2018 May;79(5):266-271. doi: 10.1016/j.humimm.2018.01.002. Epub 2018 Jan 9.

  PMID: 29330112 BACKGROUND

Study Officials

• Everett Meyer, MD

  Stanford University

  STUDY DIRECTOR

Central Study Contacts

Kevin Ly, BS

CONTACT

650-497-6057; kevinly@stanford.edu

Stephan Busque, MD

CONTACT

650-498-6189; sbusque@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In this phase 1 study, a conditioning regimen of Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donr CD34+, T cell and Recipient T regulatory Cell Transfusion in Human Leukocyte Antigen Mismatched Living Donor Kidney Transplantation will be studied

Study Record Dates

• First Submitted: May 7, 2019
• First Posted: May 9, 2019
• Study Start: February 1, 2020
• Primary Completion: August 1, 2024
• Study Completion: October 1, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)