Recruitment

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
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