Donor-Alloantigen-Reactive Regulatory T Cell (darTregs) in Liver Transplantation
Last updated on April 2022Recruitment
- Recruitment Status
- Terminated
- Estimated Enrollment
- 24
Inclusion Criteria
- Able to understand and provide informed consent
- Subjects with HCC meeting Milan criteria.
- End-stage liver disease and listed for primary solitary liver transplant
- ...
- Able to understand and provide informed consent
- Subjects with HCC meeting Milan criteria.
- End-stage liver disease and listed for primary solitary liver transplant
- If history of Hepatitis C Virus (HCV), have completed or are in current treatment for HCV AND have no detectable HCV RNA.
- Female and male subjects with reproductive potential must agree to use effective methods of birth control for the duration of the study.
- Have a calculated Model for End Stage Liver Disease (MELD) score ≤ 25 at the time of study entry/consent
Exclusion Criteria
- Development of a condition requiring chronic anti-coagulation.
- Platelets <40,000/μL
- Alanine Aminotransferase (ALT) >2.0 x upper limit of normal (ULN)
- ...
- Development of a condition requiring chronic anti-coagulation.
- Platelets <40,000/μL
- Alanine Aminotransferase (ALT) >2.0 x upper limit of normal (ULN)
- Detectable HCV RNA or less than six months after end of treatment for HCV at the time of transplantation (i.e., does not meet criteria for SVR).
- Calculated Model for End Stage Liver Disease (MELD) score >25 at the time of deceased donor liver transplant
- Last alpha-fetoprotein (AFP) obtained prior to liver transplantation >400 μg/L for candidates with Hepatocellular Carcinoma (HCC)
- Inability to taper off corticosteroids by 44 days (+/- 2 days) after transplant
- Hypersensitivity to rabbit proteins or any excipient in Thymoglobulin®.
- Insufficient depletion of recipient T cells, defined as a nadir CD3 count ≥50 cells μ/L (50 cells /mcL) or total lymphocyte count ≥ 0.1x 109/L if CD3 count is unavailable
- Absolute neutrophil count <1,200/μL
- Absence of donor spleen for any participants
- Development of a condition requiring chronic anti-coagulation.
- Positive pregnancy test for females of child bearing potential
- Explanted liver with evidence of increased risk of recurrent cancer risk (hepatocellular (HCC) tumor burden exceeding the Milan criteria; presence of vascular invasion; cholangiocarcinoma morphology)
- Unacceptable Peripheral Blood Mononuclear Cells (PBMC) product for participants enrolled in Cohorts 2, 3, or 4 per the UCSF The Human Islet and Cellular Transplant Facility (HICTF) manufacturing specifications
- Located in the intensive care unit 72 hours after transplantation
- Hemoglobin <8.0 g/dL
- Detectable circulating HCV RNA.
- Unexpected histopathology on back table liver biopsy that contraindicates the initiation of Treg supportive IS regimen.
- Clinical evidence of biliary obstruction
- Subject is < 21 or >70 years of age at the time of transplantation
- Human leukocyte antigen (HLA)-DR (DR is one of class II antigens) matched to donor at both loci
Summary
- Conditions
- Liver Transplantation
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: Non-Randomized
- Intervention Model: Parallel Assignment
- Masking: None (Open Label)
- Primary Purpose: Treatment
Participation Requirements
- Age
- Between 21 years and 70 years
- Gender
- Both males and females
Description
After liver transplantation, immunosuppressants must be taken every day to prevent the body from injuring the transplanted liver by a process called rejection. People who take these drugs may experience side effects. Studies show that some of body's cells, called T regulatory cells (Tregs), may play...
After liver transplantation, immunosuppressants must be taken every day to prevent the body from injuring the transplanted liver by a process called rejection. People who take these drugs may experience side effects. Studies show that some of body's cells, called T regulatory cells (Tregs), may play a part in accepting the transplanted liver. The investigators are learning about whether scientists can take Tregs from the blood of a liver transplant recipient and teach them to protect the transplanted liver from rejection. In the laboratory, the recipient Tregs are exposed to cells from the liver donor. Research data suggests that giving these "donor reactive" Tregs back to the transplant recipient might allow a liver transplant recipient to take lower doses of immunosuppressants, or perhaps to stop them altogether, without rejecting the liver.
Inclusion Criteria
- Able to understand and provide informed consent
- Subjects with HCC meeting Milan criteria.
- End-stage liver disease and listed for primary solitary liver transplant
- ...
- Able to understand and provide informed consent
- Subjects with HCC meeting Milan criteria.
- End-stage liver disease and listed for primary solitary liver transplant
- If history of Hepatitis C Virus (HCV), have completed or are in current treatment for HCV AND have no detectable HCV RNA.
- Female and male subjects with reproductive potential must agree to use effective methods of birth control for the duration of the study.
- Have a calculated Model for End Stage Liver Disease (MELD) score ≤ 25 at the time of study entry/consent
Exclusion Criteria
- Development of a condition requiring chronic anti-coagulation.
- Platelets <40,000/μL
- Alanine Aminotransferase (ALT) >2.0 x upper limit of normal (ULN)
- ...
- Development of a condition requiring chronic anti-coagulation.
- Platelets <40,000/μL
- Alanine Aminotransferase (ALT) >2.0 x upper limit of normal (ULN)
- Detectable HCV RNA or less than six months after end of treatment for HCV at the time of transplantation (i.e., does not meet criteria for SVR).
- Calculated Model for End Stage Liver Disease (MELD) score >25 at the time of deceased donor liver transplant
- Last alpha-fetoprotein (AFP) obtained prior to liver transplantation >400 μg/L for candidates with Hepatocellular Carcinoma (HCC)
- Inability to taper off corticosteroids by 44 days (+/- 2 days) after transplant
- Hypersensitivity to rabbit proteins or any excipient in Thymoglobulin®.
- Insufficient depletion of recipient T cells, defined as a nadir CD3 count ≥50 cells μ/L (50 cells /mcL) or total lymphocyte count ≥ 0.1x 109/L if CD3 count is unavailable
- Absolute neutrophil count <1,200/μL
- Absence of donor spleen for any participants
- Development of a condition requiring chronic anti-coagulation.
- Positive pregnancy test for females of child bearing potential
- Explanted liver with evidence of increased risk of recurrent cancer risk (hepatocellular (HCC) tumor burden exceeding the Milan criteria; presence of vascular invasion; cholangiocarcinoma morphology)
- Unacceptable Peripheral Blood Mononuclear Cells (PBMC) product for participants enrolled in Cohorts 2, 3, or 4 per the UCSF The Human Islet and Cellular Transplant Facility (HICTF) manufacturing specifications
- Located in the intensive care unit 72 hours after transplantation
- Hemoglobin <8.0 g/dL
- Detectable circulating HCV RNA.
- Unexpected histopathology on back table liver biopsy that contraindicates the initiation of Treg supportive IS regimen.
- Clinical evidence of biliary obstruction
- Subject is < 21 or >70 years of age at the time of transplantation
- Human leukocyte antigen (HLA)-DR (DR is one of class II antigens) matched to donor at both loci
Tracking Information
- NCT #
- NCT02188719
- Collaborators
- Rho Federal Systems Division, Inc.
- Investigators
- Principal Investigator: Sandy Feng, MD, PhD University of California, San Francisco Principal Investigator: Jeffrey Bluestone, PhD University of California, San Francisco Principal Investigator: Sang-Mo Kang, MD, FACS University of California, San Francisco Principal Investigator: Qizhi Tang, PhD University of California, San Francisco
- Sandy Feng, MD, PhD University of California, San Francisco Principal Investigator: Jeffrey Bluestone, PhD University of California, San Francisco Principal Investigator: Sang-Mo Kang, MD, FACS University of California, San Francisco Principal Investigator: Qizhi Tang, PhD University of California, San Francisco