Immune tolerance induction through haematopoietic chimerism after kidney donation.
Nima Nassiri, Erik Lum, Monica D Mead...
https://pubmed.ncbi.nlm.nih.gov/35934008Actively Recruiting
Phase 1
Phase 2
Age: 18Years +
All Genders
ID07269041
A Phase I Feasibility Study of Stem Cell Infusion After Conditioning to Induce Immune Tolerance in Adults With Well-Functioning HLA-Matched Living-Donor Liver Transplants
Led by University of California, Los Angeles · Updated on 2026-03-12
12
Participants Needed
1
Research Sites
208 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new approach to help adult liver transplant recipients safely stop using lifelong immunosuppressive drugs, which often cause serious side effects. This study focuses on patients who have a well-functioning liver transplant from an HLA-matched living donor. The aim is to determine if these patients can stop their immunosuppressive medications without harming the transplanted liver by using a combination of conditioning treatments and donor stem cell infusion to retrain the immune system to accept the liver as its own. Participants will undergo an outpatient conditioning regimen lasting two weeks, which includes total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG). On the final day, they will receive an infusion of donor hematopoietic stem and progenitor cells (HSPCs) collected from the same living donor. After treatment, participants will be closely monitored for graft function, donor cell presence in the blood, and signs of rejection or graft-versus-host disease. Tacrolimus, a common immunosuppressive drug, will be gradually reduced starting at six months, aiming for complete withdrawal by 10 to 12 months if certain safety and function criteria are met. During the study, patients will have regular blood tests, liver biopsies, and immune system assessments to track their progress. Researchers will measure the percentage of participants able to stop immunosuppressants by 12 months and monitor for any rejection or graft failure for up to 48 months after the stem cell infusion. The study will last several years, including long-term follow-up to ensure the safety and success of this "delayed tolerance" approach pioneered at UCLA.
CONDITIONS
Brief Title
Immune Tolerance Induction After Liver Transplantation
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Adults 18 years and older with a pre-existing liver transplant from a living donor matching 6 or more out of 12 HLA alleles
- Liver transplant performed between 12 months and 20 years before stem cell infusion
- Ability to give informed consent and agree to participate
- Liver biopsy within 4 weeks before enrollment showing no rejection
- Meets institutional criteria for stem cell infusion
- Lives or is willing to stay within 3 hours of UCLA Medical Center for first 3 months
- No known contraindications to rabbit anti-thymocyte globulin or radiation therapy
- For women of reproductive potential, pregnancy test negative and agreement to reliable contraception for 12 months after starting protocol
You will not qualify if you...
- Major ABO blood type incompatibility with donor
- Liver enzyme or bilirubin levels more than twice the upper normal limit at screening
- History of rejection in past year with current liver transplant
- History of graft-versus-host disease after liver transplant
- High levels of donor-specific antibodies at stem cell infusion
- History of multiple or multi-organ transplants
- Known allergy to rabbit proteins
- Major post-transplant complications as determined by investigator
- Active or recent malignancy within 5 years except certain low-risk or treated cancers
- Active bacterial, fungal, or mycobacterial infection
- Significant active viral infections including CMV, EBV, HCV, or HBV
- HIV or HTLV infection
- Uncontrolled serious illnesses like heart failure or arrhythmia
- Active extra-hepatic autoimmune disease needing immunosuppression
- Autoimmune disease as reason for liver transplant
- Conditions preventing informed consent or compliance
- Recent use of immunotherapy drugs within 6 months
- Use of certain liver-toxic medications unless stable for 6 months
- Active liver, gallbladder, or pancreatic diseases affecting safety or assessments
- Donor exclusions include ABO incompatibility, medical unfitness for apheresis, pregnancy or lactation, infections, psychiatric or neurological disorders, recent anticoagulant use, and recent active malignancy except certain low-risk cases
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Run-in Period
Duration - 2 weeks
Participants undergo outpatient conditioning with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG) over two weeks prior to stem cell infusion.
Multiple outpatient visits during conditioning
Treatment
Duration - 1 day
Participants receive an infusion of donor-derived hematopoietic stem and progenitor cells (HSPCs) on the final day of conditioning to induce immune tolerance.
1 infusion visit (outpatient)
Monitoring
Duration - Up to 12 months post-infusion
Participants are monitored for donor chimerism, graft function, rejection, and graft-versus-host disease while undergoing a structured taper and potential withdrawal of maintenance immunosuppression.
Regular outpatient visits for assessments and biopsies over 12 months
Long-term Monitoring
Duration - Up to 48 months post-infusion
Participants continue to be observed for liver graft rejection, graft failure, and graft-versus-host disease for up to 48 months after stem cell infusion.
Periodic outpatient visits for follow-up assessments
Trial Site Locations
Total: 1 location
1
UCLA Health 200 Medical Plaza
Los Angeles, California, United States, 90095
Actively Recruiting
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Research Team
C
Cray V. Noah, MD
R
Ruth Jones
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
Delayed immune tolerance through donor haematopoietic stem cell infusion 14 months after kidney transplantation.
Erik L Lum, Nima Nassiri, Neil Kogut...
https://pubmed.ncbi.nlm.nih.gov/39368842