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

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.

Conditions

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

Interventions

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).

Sponsors & Collaborators

• Clinical Trials in Organ Transplantation in Children

  collaborator OTHER

• Rho Federal Systems Division, Inc.

  collaborator INDUSTRY

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Sandy Feng · University of California at San Francisco

• Jeffrey Bluestone, PhD · University of California at San Francisco

• Qizhi Tang, PhD · University of California at San Francisco

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-06

Primary Completion

2019-12-16

Completion

2019-12-16

Countries

• United States

Study Locations