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NCT Number: NCT03943238

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

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.

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Key information

Conditions

Living Donor Kidney Transplantation

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Stanford University, Palo Alto, California, United States

Loading trial locations.

About this study

It has been demonstrated that hematopoietic mixed chimerism or the coexistence of both donor and recipient immune cells can lead to tolerance to the graft in absence of graft versus host disease (GVHD). The goal of this pilot study is to determine if recipients of living donor kidney transplant can be successfully withdraw from immunosuppressive drugs. The patients will receive a preparatory regimen consisting of TLI and a low single dose of TBI and ATG following their kidney transplantation. Two weeks later, they will receive purified hematopoietic stem cells (CD34+) and Tcells that have been collected 6 weeks prior from their kidney donor. Regulatory T cells (Tregs) that have been collected from the recipient prior to the transplantation and expanded in vitro will be infuse the following day to enhance the chance of engraftment of the donor bone marrow cells. If chimerism develops and persists, the immunosuppressive drug will be tapered and stop. Mycophenolate mofetil (MMF) will be stopped 12 months after transplantation and if the chimerism remains stable, tacrolimus will be stopped 6 months later. The dose of Tregs will be escalated if the % of donor chimerism is not at least 25% during the first 60 days.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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.

Treatment and study plan

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.

Primary outcomes

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

    Time frame: Month 18

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

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

    Time frame: Month 18

Secondary outcomes

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

    Time frame: up to 2 years

  2. Count of participants with bacterial, viral, or fungal infections

    Time frame: up to 2 years

Study contacts

Contact information is provided by the study sponsor or research team.

Kevin Ly, BS

CONTACT

[email protected]

650-497-6057

Stephan Busque, MD

CONTACT

[email protected]

650-498-6189

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Collaborators

  • California Institute for Regenerative Medicine (CIRM)
  • Northwestern University

Registry information

Official study title

Phase 1 Study of Total Lymphoid Irradiation, Total Body Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+, T-cell and Recipient T Regulatory Cell Transfusion in Human Leukocyte Antigen Mismatched Living Donor Kidney Transplantation

Important dates

Study start
2020
Primary completion
2029
Study completion
2029
First posted
May 9, 2019
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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