A Phase I Feasibility Study of HSPC Infusion Following Total Lymphoid Irradiation and Anti-thymocyte Globulin in Patients With a Pre-existing, Well-functioning HLA-matched Living-donor Liver Transplant to Induce Immune Tolerance.
University of California, Los Angeles
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."
Description
This study seeks to determine if patients with a pre-existing, well-functioning liver transplant from an HLA-matched living donor can be withdrawn from maintenance immunosuppressive medications without compromising allograft function through hematopoietic stem and progenitor cell (HSPC) infusion from the same donor. HSPC infusion will be preceded by a conditioning regimen of total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG) that takes course over two weeks, with HSPC infusion being on the final day. This entire protocol will take place in the outpatient setting. At se…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Recipient Inclusion Criteria: 1. 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. 2. Pre-existing living-donor liver transplant must be 12 months to 20 years from date of scheduled HSPC infusion. 3. Agreement to participate in the study and ability to give informed consent. 4. Liver biopsy within 4 weeks of enrollment without signs of rejection. 5. Meets institutional criteria for HSPC infus…
Interventions
- BiologicalDonor Hematopoietic Stem and Progenitor Cell Infusion
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.
Location
- UCLA Health 200 Medical PlazaLos Angeles, California