DCreg in Living Donor Liver Transplantation

Living Donor Liver Transplantation Clinical Trial

Official title:

Safety and Preliminary Efficacy of Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03164265
• Other study ID #: STUDY19020267
• Secondary ID: IND#17271
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 30, 2017
• Est. completion date: December 2024

Study information

• Verified date: September 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Living Donor Liver Transplantation

Intervention

Biological:
• Regulatory Donor-Derived Dendritic Cell infusion
Regulatory dendritic cells that were prepared from a donor leukapheresis will be infused into liver transplant recipients 7 days prior to surgery

Locations

Country	Name	City	State
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Angus W. Thomson PhD DSc	University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Safety Events	1. Safety: Safety will be determined by assessing the proportion of subjects experiencing the following events: i) CTCAE Grade 4 or higher infusion reaction; ii) CTCAE Grade 4 or higher infection; iii) Malignancy other than non-melanoma skin cancer or HCC recurrence; iv) Rejection resulting in recipient death or retransplantation; v) Biopsy-proven severe acute rejection; vi) Any grade chronic rejection; vii) Non-surgical graft loss; viii) Recipient death;	6 years
Primary	Preliminary Efficacy	Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance	2.5 years
Secondary	Donor Specific Antigen (DSA) levels	DSA levels early (<6 weeks) and late (> 6 weeks) after transplantation	6 years
Secondary	Change in renal function	Change in renal function	1 year post-transplantation (prior to weaning) 4.5 years post transplantation
Secondary	Change in Quality of Life	Change in Quality of Life as measured by the Short Form 36 (SF-36) Quality of Life questionnaire	1 year post-transplantation (prior to weaning) 4.5 years post transplantation
Secondary	Change in cardiovascular risk factors	Change in cardiovascular risk factors including incidence of hypertension necessitating medication, post-transplant diabetes, hyperlipidemia, hypercholesterolemia	1 year post-transplantation (prior to weaning) 4.5 years post transplantation