Retro-active Immunological Tolerance in Patients With Well-functioning Pre-existing HLA-identical Kidney Transplants

Chronic Kidney Diseases Clinical Trial

Official title: A Single-armed, Unblinded, Non-randomized Feasibility Study of Hematopoietic Stem Cell Infusion Following a Conditioning Regimen of Total Lymphoid Irradiation (TLI) and Anti-thymocyte Globulin (ATG) in Patients With a Pre-existing, Well-functioning HLA-identical Kidney Transplant

Status Recruiting

Clinical Trial Summary

The study seeks to determine if patients with a pre-existing, well-functioning kidney transplant from a HLA-identical living donor can be withdrawn from immunosuppressive medications without compromising allograft function through hematopoietic stem cell (HPSC) infusion from the same donor. HPSC infusion will be preceded by a conditioning regimen of total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG).

Clinical Trial Description

Immunological tolerance through combined kidney and HPSC transplant has been demonstrated at few centers of excellence within the United States. The ultimate aim of these protocols is to liberate patients from lifelong immunosuppression. Thus far, protocols have been limited to HLA-identical donor recipient pairs, undergoing simultaneous kidney transplant and HPSC infusion. In all protocols, the recipient undergoes a conditioning regimen to optimize engraftment. Our protocol employs a conditioning regimen of TLI and ATG.

There are many more patients with pre-existing well-functioning HLA-identical kidney transplants than those who present de novo for participation in tolerance trials. Despite this, post hoc tolerance induction through HPSC infusion in patients with a pre-existing kidney transplant has not yet been performed. Given the demonstrated success of tolerance protocols in simultaneous haploidentical kidney and HPSC transplant, the next logical step is to demonstrate that tolerance can be induced in the much greater subset of patients with pre-existing kidney transplants.

This study employs an established protocol for immunological tolerance induction in patients with a pre-existing, well- functioning kidney transplant from their haploidentical donor. These patients will undergo a conditioning with TLI and ATG, followed by infusion of HPSC from the same HLA-identical donor that provided the original kidney. The Investigators call this process "retroactive tolerance induction."

The investigators will evaluate whether recipients can be withdrawn from immunosuppressive drugs without compromising allograft function. At serial time points, (1) graft function will be monitored, and (2) chimerism will be measured in recipient whole blood and white blood cell subsets. Weaning of tacrolimus will begin at 6 months, with a goal of drug discontinuation within 12 months if the following conditions are met: (1) chimerism (defined as ≥1% donor type cells among the T cells, B cells, NK cells, and granulocytes) is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) stable graft function (defined as eGFR >30 mL/min and no greater than sustained 30% change over 3 months from baseline) without clinical rejection episodes is maintained, and (3) there is no evidence of graft vs. host disease (GVHD). ;

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• End Stage Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Kidney Transplant Failure and Rejection
• Renal Insufficiency, Chronic

• NCT number: NCT05525507
• Study type: Interventional
• Source: University of California, Los Angeles
• Contact: Ruth Wynne Jones
• Phone: 424-402-9564
• Email: rwynnejones@mednet.ucla.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: December 21, 2022
• Completion date: September 2026