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ACTIVE NOT RECRUITING

NCT04208919

PHASE1/PHASE2

Delayed Infusion of DCreg in Living Donor Liver Transplantation

Sponsor: Angus W. Thomson PhD DSc

View on ClinicalTrials.gov

Summary

Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients who are between 1 and 3 years after transplantation and meet specific criteria (no positive crossmatch, no clinically treated rejection within 2 years preceding enrollment, permissive liver function tests (LFTs) within 30 days preceding enrollment, no prior liver biopsy showing significant fibrosis or ductopenia\*) will be enrolled and will undergo a protocol liver biopsy unless they have had a permissive liver biopsy\*\* within 90 days of anticipated immunosuppression weaning. Those patients with permissive liver biopsy\*\* will then receive a single infusion of donor-derived DCreg and will remain on their current standard of care (SOC) immunosuppression. One week after DCreg infusion, immunosuppression weaning will be initiated. Recipients will be slowly weaned off immunosuppression. Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression. They will undergo a liver biopsy at 1 yr and 3 yrs after immunosuppression withdrawal. Participants who are removed from the study protocol at any time will return to standard of care but will continue to be followed by the study team and will undergo a liver biopsy at the end of the study. \* Permissive LFTs are defined as ALT, AST and total bilirubin \< 2.5 times the upper limit of normal. \*\*A permissive biopsy is based on 2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology (the criteria detailed in Table 8, Demetris et al. 2016).

Official title: Safety and Preliminary Efficacy of Delayed Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplant (LDLT) Recipients

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2019-12-18

Completion Date

2026-06

Last Updated

2025-08-12

Healthy Volunteers

Conditions

Living Donor Liver Transplantation

Interventions

BIOLOGICAL

Donor-derived DCreg

Regulatory dendritic cells that were prepared from a donor leukapheresis will be infused into liver transplant recipients 7 days prior to the start of immunosuppression weaning.

Inclusion Criteria: Donor 1. Able to understand and provide informed consent 2. Male or female age 18 or older at the time of enrollment 3. Have no contraindication to leukapheresis 4. For females of childbearing potential, a negative urine or serum pregnancy test 5. No live vaccines within 12 weeks prior to leukapheresis 6. Negative health history for risk factors related to Creutzfeldt-Jakob disease 7. Negative for West Nile Virus(a) 8. Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(a) 9. Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(a) 1. does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient. Recipients 1. Low risk LDLT recipients, irrespective of gender, race, or ethnic background. Low risk is defined by absence of exclusion criteria (below). 2. Age 18 or older at the time of enrollment 3. Underwent de novo (first) liver transplant 1 to 3 years prior to enrollment 4. Female subjects of childbearing potential must have a negative pregnancy test upon study entry. 5. Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until 1 year after completion of immunosuppression withdrawal. Exclusion Criteria: Recipients 1. History of positive crossmatch (performed prior to transplant) 2. Clinically treated rejection episode within 2 years prior to enrollment 3. Non-permissive LFTs within past 1 month 4. Repeat liver transplant 5. Prior other solid organ transplant 6. Significant co-morbid conditions such as severe heart or lung disease 7. Following etiology of liver disease: Primary Sclerosing Cholangitis (PSC), autoimmune, Primary Biliary Cirrhosis (PBC) 8. If prior history of Hepatitis B or C (HBV or HCV) infection, Hepatitis B or C Virus (HBV or HCV) viral load positive at the time of enrollment (successfully treated HBV or HCV patients are not excluded) 9. Positive antigen-antibody immunoassay for HIV-1/2 10. Any prior biopsy showing significant fibrosis or ductopenia. 11. Any medical condition that the investigator deems incompatible with participation in the trial.

Locations (1)

UPMC

Pittsburgh, Pennsylvania, United States