Clinical trial NCT03164265: DCreg in Living Donor Liver Transplantation
Official title: Safety and Preliminary Efficacy of Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Living Donor Liver Transplantation
Keywords: Regulatory Dendritic Cells
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2017-05-23
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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 will receive a single infusion of donor-derived DCreg 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet specific criteria be weaned off Tac over 6 months . Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression.

Detailed description: 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 will receive a single infusion of donor-derived DCreg with concurrent mycophenolic acid (MPA) therapy (1/2 dose) 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria (no rejection and permissive liver function tests (LFTs)) will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet the criteria of no rejection and permissive LFTs will undergo a protocol liver biopsy and proceed to Tac weaning over 6 months if liver biopsy is permissive. 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 may undergo a liver biopsy at the end of the study (4.5 yrs after transplantation). For subjects who return to standard of care (on immunosuppression at end of study), the year 4.5 biopsy will be optional.

Eligibility criteria: Inclusion Criteria:

Donors

1. Able to understand and provide informed consent;
2. Male or female between the ages of 18-55;
3. Meet all standard institutional and UNOS criteria for liver donation;
4. For females of childbearing potential, a negative urine or serum pregnancy test;
5. Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(\*)
6. Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(\*)

Recipients

1. Low risk recipient approved for LDLT, irrespective of gender, race, or ethnic background. Low risk is defined by absence of exclusion criteria (below).
2. Between ages 18 and 65 years
3. Undergoing de novo (first) liver transplant
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.

(\*)does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient.

Primary outcomes:
measure: Proportion of Safety Events
timeFrame: 6 years
measure: Preliminary Efficacy
timeFrame: 2.5 years
Secondary outcomes:
measure: Donor Specific Antigen (DSA) levels
timeFrame: 6 years
measure: Change in renal function
timeFrame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation
measure: Change in Quality of Life
timeFrame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation
measure: Change in cardiovascular risk factors
timeFrame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Abhinav Humar, MD
role: PRINCIPAL_INVESTIGATOR
References: