Donor Alloantigen Reactive Tregs (darTregs) for Calcineurin Inhibitor (CNI) Reduction
Condition: Liver Transplant Recipient; Living Donor (of the Respective Liver Transplant Recipient)
Study type: Interventional
Phase: Phase 1/Phase 2

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

Detailed description: 
      Doctors give drugs called immunosuppressants (IS) to people who receive a liver transplant.
      IS must be taken every day to prevent the body from injuring the transplanted liver by a
      process called rejection. Liver transplant recipients usually have to take these drugs for
      the rest of their lives. These drugs have harmful side effects. Researchers are looking for
      ways to keep a transplanted liver working normally with as little IS medications as possible.
      Finding a way to lower and then stop these medications will allow the liver recipient to
      avoid unwanted side effects.

      Another area of research looks at how blood cells work to reject or accept an organ
      transplant. Studies show that some of the recipient's own cells, called T regulatory cells
      (Tregs), may play a part in accepting the transplanted liver and preventing rejection.

      A recipient's Tregs can be grown in the laboratory to increase their number. Exposing the
      recipient's Tregs to the liver donor's cells will stimulate the Tregs that recognize the
      liver donor to grow vigorously. Giving these "donor reactive" Tregs back to the transplant
      recipient through a vein (intravenously) might allow a liver transplant recipient to take
      lower doses of IS, or perhaps to stop them altogether, without rejecting the liver.

      The study team will collect information about the Treg infusion, liver tests and drug doses
      during IS withdrawal, and any problems that may arise in the study. Blood, liver tissue, and
      buccal (cheek) cells will be collected for research tests.
    

Intervention name(s): darTregs; Acetaminophen; Diphenhydramine; Immunosuppression (IS) Withdrawal; Study Mandated Procedures
Intervention type(s): Biological; Drug; Drug; Drug; Procedure
Intervention description(s): A single intravenous infusion as described administered over a 20-30 minute interval with close monitoring prior to, during, and after the infusion.; Pre-medication for darTregs infusion. A dose of 15 mg/kg will be administered 30 to 60 minutes prior to the darTregs infusion.; Pre-medication for darTregs infusion. A dose of 1-2 mg/kg diphenhydramine will be administered 30 to 60 minutes prior to the darTregs infusion.; Subjects:1.) who fulfill study eligibility criteria will withdraw IS 2.) enter the study on calcineurin inhibitor (CNI) monotherapy or a CNI-based regimen with either Prednisone or MMF as a second IS medication 3.) will proceed with changes in CNI dosing according to the protocol's CNI withdrawal algorithm.During the last 2 weeks of IS withdrawal (e.g., Step 2 in algorithm -CNI reduced 25%-"pre darTregs"), a single dose of darTregs will be infused IV. The subject will then, if eligible, proceed with IS withdrawal within 2 weeks after the infusion. Eligible subjects meeting the primary endpoint of 75% reduction in CNI from baseline after darTregs will be offered the opportunity to continue IS withdrawal until complete discontinuation of IS.; Blood draws (venipuncture); collection of peripheral blood mononuclear cells (PBMCs) by a procedure known as leukapheresis or venipuncture; buccal (cheek) swab for HLA typing; liver biopsies (per protocol and for cause).
Other intervention name(s): Donor Alloantigen Reactive Tregs; Diphenhydramine Hydrochloride; IS Withdrawal; CNI based IS regimen
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Regulatory T Cells ( Treg); Donor Alloantigen Reactive Tregs (darTregs); Liver Transplant; Alloantigen Reactive Tregs; Calcineurin Inhibitors (CNI); immunosuppressants (IS)