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.
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.
• 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.
• Males and females ages 18 years and older meeting the HLA-matching requirements specified in the Recipient Inclusion Criteria above.
• Must meet the following criteria for HSPC donation:
‣ Hgb: \> 11 g/dl
⁃ Plt: \> 80,000/µL
⁃ WBC: \> 3,000/µL