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DCreg in Living Donor Liver Transplantation

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ClinicalTrials.gov Identifier: NCT03164265
Recruitment Status : Enrolling by invitation
First Posted : May 23, 2017
Last Update Posted : October 13, 2017
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Angus W. Thomson, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Living Donor Liver Transplantation Biological: Regulatory Donor-Derived Dendritic Cell infusion Phase 1 Phase 2

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 be continue to be followed by the study team and will undergo a liver biopsy at the end of the study (4.5 yrs after transplantation).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Safety and Preliminary Efficacy of Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplantation
Actual Study Start Date : August 30, 2017
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine



Intervention Details:
  • 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
    Other Name: DCreg


Primary Outcome Measures :
  1. Safety [ Time Frame: 6 years ]
    1. Safety: Safety will be determined by assessing the proportion of subjects who experience 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;

  2. Preliminary Efficacy [ Time Frame: 2.5 years ]
    Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance


Secondary Outcome Measures :
  1. Donor Specific Antigen (DSA) levels [ Time Frame: 6 years ]
    DSA levels early (<6 weeks) and late (> 6 weeks) after transplantation

  2. Change in renal function [ Time Frame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation ]
    Change in renal function

  3. Change in Quality of Life [ Time Frame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation ]
    Change in Quality of Life as measured by the Short Form 36 (SF-36) Quality of Life questionnaire

  4. Change in cardiovascular risk factors [ Time Frame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation ]
    Change in cardiovascular risk factors including incidence of hypertension necessitating medication, post-transplant diabetes, hyperlipidemia, hypercholesterolemia



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03164265


Locations
United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15261
Sponsors and Collaborators
Angus W. Thomson
University of Pittsburgh
Investigators
Principal Investigator: Abhinav Humar, MD University of Pittsburgh

Responsible Party: Angus W. Thomson, Distinguished Professor of Surgery and Immunology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03164265     History of Changes
Other Study ID Numbers: PRO16110490
IND#17271 ( Other Identifier: FDA )
First Posted: May 23, 2017    Key Record Dates
Last Update Posted: October 13, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Angus W. Thomson, University of Pittsburgh:
Regulatory Dendritic Cells