Liver Transplantation With Tregs at MGH

Summary

This is a single-center, prospective, open-label, non-randomized clinical trial exploring cellular therapy to facilitate immunosuppression withdrawal in liver transplant recipients.

Conditions

• Liver Transplant

Interventions

BIOLOGICAL

arTreg-CSB

Participants will receive a single dose of Treg product (arTreg-CSB). The target dose is 2.5 to 125 x 10\^6 total cells. If a minimum arTreg-CSB dose of 1 to \< 2.5 x 10\^6 cells, the product will be infused. If the dose obtained after product manufacture is \< 1 x 10\^6 cells, the product will not be infused. When the dose obtained after product manufacture is \> 125 x 10\^6 cells, a dose aliquot will be prepared so that the administered dose will be ≤ 125 x 10\^6 cells, and ≥ 2.5 to 125 x 10\^6 total cells. Method of receipt: peripheral intravenous (IV) infusion, administered over 15 to 30 minutes.

PROCEDURE

leukapheresis

Leukapheresis will be the method employed to recover peripheral blood mononuclear cells (PBMCs) from the allograft recipient. The recipient will undergo the procedure prior to initiating the cyclophosphamide conditioning regimen. Procedure 72 to 120 hours prior to Treg product (arTreg-CSB) IV infusion.

DRUG

cyclophosphamide

40 mg/kg administered intravenously (IV) within 24 to 72 hours prior to Treg product (arTreg-CSB) infusion.

DRUG

mesna

Mesna is administered intravenously to inhibit hemorrhagic cystitis induced by cyclophosphamide. Administration of mesna is per institutional practice with cyclophosphamide.

DRUG

everolimus

EVR, an immunosuppressant (IS), is approved by the FDA for the prophylaxis of allograft rejection in adults receiving a liver transplant. Between day 30 and wk. 48 post-transplant, participant evaluation for eligibility to be converted to an EVR-based IS regimen will occur. At the start of conversion from tacrolimus (TAC) to EVR IS:EVR will be started at 1.5 mg taken by mouth BID, with dose adjusted to achieve a trough blood level of 5-8 ng/mL. Once an EVR trough level of ≥ 5 ng/mL is achieved, baseline TAC dose will be reduced to achieve a trough level of 3-5 ng/mL. When target EVR and TAC levels are achieved/ maintained over two consecutive measurements, and liver function tests, ALT and GGT, are ≤50 U/L, participants will be considered successfully converted to EVR-based IS regimen. EVR doses will be administered, monitored and adjusted over time, per protocol.

Sponsors & Collaborators

• Immune Tolerance Network (ITN)

  collaborator NETWORK

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• James F. Markmann, MD, PhD · University of Pennsylvania Medical Center: Transplantation

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

2019-03-29

Primary Completion

2026-02-06

Completion

2027-04-06

FDA Drug

Yes

Countries

• United States

Study Locations