NCT02474199

Donor Alloantigen Reactive Tregs (darTregs) for Calcineurin Inhibitor (CNI) Reduction

Safety of Donor Alloantigen Reactive Tregs to Facilitate Minimization and/or Discontinuation of Immunosuppression in Adult Liver Transplant Recipients (CTOTC-12)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Liver Transplant Recipient
• Living Donor (of the Respective Liver Transplant Recipient)

Interventions

Type	Name	Description
BIOLOGICAL	darTregs	A single intravenous infusion as described administered over a 20-30 minute interval with close monitoring prior to, during, and after the infusion.
DRUG	Acetaminophen	Pre-medication for darTregs infusion. A dose of 15 mg/kg will be administered 30 to 60 minutes prior to the darTregs infusion.
DRUG	Diphenhydramine	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.
DRUG	Immunosuppression (IS) Withdrawal	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.
PROCEDURE	Study Mandated Procedures	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).

Timeline

• Start date: 2016-06-06
• Primary completion: 2019-12-16
• Completion: 2019-12-16
• First posted: 2015-06-17
• Last updated: 2021-02-09
• Results posted: 2021-02-09

Locations

3 sites across 1 country: United States