A Study of Donated Alloantigen Reactive Regulatory T Cells for Reducing or Discontinuing Immune System Suppression in Liver Transplant Patients

Overview

  • Study type

    Interventional
  • Study phase

    I/II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 14-009783
    NCT ID: NCT02474199
    Sponsor Protocol Number: CTOTC-12

About this study

This research study is for liver transplant recipients and their respective living donors. The purpose of this study is to see if it is safe for liver recipients to receive one dose of donor reactive T regulatory cells (Tregs), and if the Tregs allows a liver recipient to take less, or completely stop medications normally taken after receiving an organ transplant.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

 Inclusion Criteria

  • Must meet all criteria below to receive darTregs infusion
    • Stable liver tests, defined as ALT and either alkaline phosphatase or GGT either within normal limits OR ≤ 1.5 X baseline
    • No detectible circulating EBV or CMV DNA 4 weeks prior to Treg infusion
    • For subjects with hepatitis B virus (HBV), no detectible circulating HBV DNA
  • Is eligible to resume IS withdrawal after darTregs infusion if all criteria below are met
    • Subject received at least 100 x 10^6 darTregs
    • ALT and either alkaline phosphatase or GGT remain within normal limits or ≤ 1.5 x baseline after darTregs infusion
    • For subjects with elevated liver tests as defined above, local pathology reading of liver biopsy 6-10 days after darTregs infusion is without AR according to Banff criteria
    • IS withdrawal resumes no later than 14 days after darTregs infusion
    • Site principal investigator determines it is acceptable for the study subject to resume IS withdrawal

Exclusion Criteria

  • Any of these criteria are not eligible for study enrollment
    • Transplant for liver disease secondary to hepatitis C or autoimmune disease (e.g. autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis), or Hepatocellular Carcinoma (HCC)
    • Matched at both human leukocyte antigen (HLA)-DR loci to the donor
    • Organ, tissue or cell transplant prior to or after the primary solitary living donor liver transplant
    • For subjects with hepatitis B, detectible hepatitis B virus (HBV) DNA
    • History of malignancy within 5 years of enrollment
      • History of adequately treated in-situ cervical carcinoma and/or skin cancer (basal or squamous cell) will be permitted
    • Serologic evidence of human immunodeficiency 1 or 2 infection
    • Epstein Barr Virus (EBV) seronegativity (EBV naïve) if living donor is EBV seropositive
    • Cytomegalovirus (CMV) seronegativity (CMV naïve) if living donor is CMV seropositive
    • Calculated Glomerular filtration rate (GFR) less than 50 mL/min/1.73m^2 at the time of enrollment
    • An episode of Acute Rejection (AR) within one year of enrollment
    • Systemic illness requiring or likely to require recurrent or chronic immunosuppression (IS) drug use
    • Any chronic condition for which anti-coagulation cannot be safely interrupted for liver biopsy
    • Positive pregnancy test
    • Peripheral blood Tregs <30/μL at screening
    • Participation in any other studies that involved investigational drugs or regimens in the preceding year
    • Any other condition, in the investigator's judgment, that increases the risk of darTregs infusion or prevents safe trial participation
    • Unwilling or unable to adhere to study requirements and procedures
    • Screening liver biopsy with any of the following histological criteria, as determined by the reading of a central pathologist
  • Any of these criteria are not eligible for darTregs infusion
    • Diagnosis of AR after initiation of IS withdrawal
    • Any vaccination given within 28 days prior to Treg collection for Treg production
    • Receipt of a vaccination within 14 days prior to Treg infusion
    • Unacceptable darTregs product
    • Positive pregnancy test
    • Clinical evidence of viral syndrome less than 7 days prior to darTregs infusion

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Timucin Taner, M.D., Ph.D.

Open for enrollment

Contact information:

Britten Block

(507)293-4773

Block.Britten@mayo.edu