Immune Tolerance Induction After Liver Transplantation

NCT07269041 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-25-2369
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is being conducted to help liver transplant recipients safely discontinue toxic immunosuppressive drugs years after surgery. Lifelong use of these drugs is the current standard, but they come with life-threatening side effects. UCLA has pioneered this "Delayed Tolerance" approach, achieving success in numerous kidney recipients now living drug-free. The process uses a conditioning regimen followed by donor stem cell infusion to retrain the immune system to accept the liver as "self."

Conditions

Liver Transplantation; Immune Tolerance; Immune Tolerance/Drug Effects; Graft Survival; Hematopoietic Stem Cell; Chimerism; Immunosuppression After Liver Transplantation; Immunosuppression Disorders; End Stage Liver Disease

Keywords

Liver Transplantation; Immune Tolerance; Hematopoietic Stem Cell Infusion; Chimerism; Mixed Chimerism; Total Lymphoid Irradiation; Antithymocyte Globulin; Immunosuppression Withdrawal; Living Donor Liver Transplant; Tolerance Induction; Delayed Immune Tolerance; Retroactive Immune Tolerance; Immunosuppression Toxicity

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects weaned off liver transplant immunosuppressants at 12 months after HSPC infusion

  The percentage of subjects who successfully discontinue all liver transplant immunosuppressant medications at 12 months after HSPC infusion.

  12 months post-HSPC infusion.

Secondary Outcomes (3)

• Liver graft rejection within 48 months post-HSPC infusion

  Up to 48 months post-HSPC infusion.

• Graft failure

  Up to 48 months post-HSPC infusion.

• Incidence of GVHD

  Up to 48 months post-HSPC infusion.

Other Outcomes (8)

• Chimerism persistence

  12, 24, 36, and 48 months post-HSPC infusion.

• Incidence of acute or chronic GVHD (detailed)

  Up to 48 months post-HSPC infusion

• Liver function

  12, 24, 36, and 48 months post-HSPC infusion.

Study Arms (1)

Tolerance Induction Arm

EXPERIMENTAL

Adult recipients with a pre-existing, well-functioning HLA-matched living-donor liver transplant from the same donor will undergo outpatient conditioning with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG), followed by infusion of mobilized donor hematopoietic stem and progenitor cells (separate CD34+ and CD3+ fractions). After HSPC infusion, participants will be monitored for donor chimerism, graft function, rejection, and GVHD, and will undergo a structured taper of maintenance immunosuppression with the goal of complete withdrawal if donor chimerism is present and protocol criteria are met.

Biological: Donor Hematopoietic Stem and Progenitor Cell Infusion

Interventions

Donor Hematopoietic Stem and Progenitor Cell Infusion BIOLOGICAL

Participants with a pre-existing, well-functioning HLA-matched living-donor liver transplant from the same donor will receive a delayed infusion of donor-derived hematopoietic stem and progenitor cells (HSPCs). Donors undergo mobilization and apheresis to collect peripheral blood stem cells, which are processed to generate a CD34+ cell product with an accompanying defined CD3+ T-cell dose. Recipients receive outpatient conditioning with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG) prior to infusion. The goal of the intervention is to induce tolerance by achieving durable mixed chimerism and enable structured withdrawal of maintenance immunosuppression.

Also known as: Donor HSPC Infusion

Tolerance Induction Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ages 18 years and older with a pre-existing liver transplant from a living donor with a donor-recipient match at 6 or more out of 12 alleles across the HLA-A, -B, -C, -DR, -DQ, and -DP loci, as determined by high-resolution HLA typing.
• Pre-existing living-donor liver transplant must be 12 months to 20 years from date of scheduled HSPC infusion.
• Agreement to participate in the study and ability to give informed consent.
• Liver biopsy within 4 weeks of enrollment without signs of rejection.
• 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 months of the trial at the physician's discretion.
• No known contraindication to administration of rATG or radiation therapy.
• If subject is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status), subject 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 following initiation of the tolerance protocol.

You may not qualify if:

• Major ABO incompatibility with donor.
• Any of the following labs \> 2.0 times the upper limit of normal on screening: AST, ALT, ALP, GGT or TBil.
• History of rejection with current HLA-matched liver transplant within the last year.
• History of GVHD following liver transplant.
• Positive Class II HLA Donor-Specific Antibody (DSA) or class I DSA specificity above 5,000 MFI at the time of the stem cell infusion.
• History of multi-organ transplantation, either simultaneous or as separate events.
• History of more than one liver transplant.
• Known allergy to rabbit proteins.
• History of a major post-transplant complication at investigator discretion.
• History of active malignancy within the past 5 years except for:
• Malignancy that has not required treatment in the past 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, DCIS).
• Active bacterial, fungal or mycobacterial infection.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Health 200 Medical Plaza

Los Angeles, California, 90095, United States

RECRUITING

Related Publications (2)

• Nassiri N, Lum E, Mead MD, Raldow AC, Kogut N, Veale JL. Immune tolerance induction through haematopoietic chimerism after kidney donation. Lancet. 2022 Aug 6;400(10350):e2. doi: 10.1016/S0140-6736(22)00914-X. No abstract available.

  PMID: 35934008 BACKGROUND

• Lum EL, Nassiri N, Kogut N, Oliai C, Raldow A, Reed EF, Veale JL. Delayed immune tolerance through donor haematopoietic stem cell infusion 14 months after kidney transplantation. Lancet. 2024 Oct 5;404(10460):1346. doi: 10.1016/S0140-6736(24)01935-4. No abstract available.

  PMID: 39368842 BACKGROUND

Related Links

• UCLA Immune Tolerance Website

MeSH Terms

Conditions

End Stage Liver Disease

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Jeffrey Veale, MD

  UCLA Health

  PRINCIPAL INVESTIGATOR

• Cray V. Noah, MD

  UCLA Health

  STUDY DIRECTOR

Central Study Contacts

Cray V. Noah, MD

CONTACT

310-267-7727; cnoah@mednet.ucla.edu

Ruth Jones

CONTACT

424-402-9564; tolerance@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: Principal Investigator

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 8, 2025
• Study Start: February 20, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2033
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)