Delayed Immunological Tolerance in Patients With Well-functioning Pre-existing HLA-matched Kidney Transplants

NCT05525507 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Delayed Tolerance
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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determine if patients with a pre-existing, well-functioning kidney transplant from a HLA-identical living donor can be withdrawn from immunosuppressive medications without compromising allograft function through hematopoietic stem cell (HPSC) infusion from the same donor.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).

Conditions

End Stage Kidney Disease; Immunological Tolerance; Kidney Transplant Failure and Rejection; Chronic Kidney Diseases

Keywords

immunological tolerance; kidney transplant; tolerance; end stage kidney disease; end stage renal disease; chronic kidney disease

Outcome Measures

Primary Outcomes (1)

• Incidence of successful discontinuation of immunosuppression

  To determine whether patients with pre-existing kidney transplants from a haploidentical living donor can be withdrawn from immunosuppressive drugs while maintaining stable graft function within 12 months of hematopoietic stem cell infusion from the same HLA-identical living donor, preceded by conditioning with TLI and ATG.

  12 months

Secondary Outcomes (2)

• Incidence of allograft rejection

  48 months

• Graft survival

  24 months

Study Arms (1)

Immune tolerance in HLA-identical kidney transplant recipient

EXPERIMENTAL

We seek to establish immunological tolerance in patients with a pre-existing, well- functioning kidney transplant from an HLA-identical donor. Patients will undergo conditioning with TLI and ATG, followed by infusion of hematopoietic stem cells from the same donor . We will evaluate whether recipients can be withdrawn from immunosuppressive drugs without compromising allograft function. At serial time points, graft function will be monitored, and chimerism will be measured. 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, (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) no evidence of graft vs. host disease (GVHD).

Combination Product: Conditioning and Stem cell infusion

Interventions

Conditioning and Stem cell infusion COMBINATION_PRODUCT

Patients will undergo a conditioning with TLI and ATG, followed by infusion of hematopoietic stem cells from the same HLA-identical donor that provided the original kidney

Immune tolerance in HLA-identical kidney transplant recipient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ages 18 years and older with a pre- existing kidney transplant from an HLA-matched living donor.
• Pre-existing living kidney transplant must be within 3 months to 5 years from date of scheduled HPSC infusion.
• No history of rejection with current HLA matched kidney transplant.
• Recipient is without post-transplant major complications, including de novo malignancy, active infection or rejection.
• Stable renal function determined per investigator discretion.
• Agreement to participate in the study and ability to give informed consent.
• Meets institutional criteria for HSPC infusion.
• Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion.
• No known contraindication to administration of rATG or radiation.
• If participant is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) participant must be confirmed not pregnant by a serum or urine pregnancy test) and must agree to practice a reliable form of contraception including hormonal treatments, barrier methods or intrauterine device for at least 12 months post-transplant.
• Karnofsky Performance Score (KPS) ≥ 70.
• Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
• Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal.
• Adequate social support based on evaluation by the UCLA bone marrow and/or renal transplant team.

You may not qualify if:

• Donor is identical twin.
• Major ABO incompatibility with donor
• Positive HLA Donor-Specific Antibody (DSA)
• History of multi-organ transplantation
• History of rejection with current HLA-matched kidney transplant
• Known allergy to rabbit proteins
• History of post-transplant major complications, including de novo malignancy, active/chronic infection or rejection, with the exception of low risk, early-stage malignancy with
• ≥90% 5-year survival not receiving chemotherapy or immunotherapy and non-melanomatous skin cancer.
• History of active malignancy within the past 5 years with the exception:
• Low risk cancer on active surveillance
• Malignancy treated with curative intent with no known active disease \>2 years before the first dose of study treatment and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ, and DCIS)
• Worsening renal functioning over preceding 3-month interval determined per investigator discretion.
• Pregnant (confirmed by urine or serum pregnancy test) or lactating.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA

Los Angeles, California, 90095, United States

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic; Rejection, Psychology; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Social Behavior; Behavior

Study Officials

• Jeffrey Veale, MD

  Professor of Urology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Wynne Jones

CONTACT

424-402-9564; rwynnejones@mednet.ucla.edu

Jenny Lester, MPH

CONTACT

310-794-9728; jlester@mednet.ucla.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: Professor

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: December 21, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)