NCT03577431

Liver Transplantation With Tregs at MGH

A Phase I/II Drug Withdrawal Study of Alloantigen-Specific Tregs in Liver Transplantation (ITN073ST)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 9 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

The researchers in this study plan to enroll 9 participants who will receive at least the target Treg product (arTreg-CSB) dose of 2.5 x 10\^6 cells. Participants who receive at least 1 x 10\^6 cells but \< 2.5 x 10\^6 cells as a result of low cell yield will be included in intent-to-treat (ITT) analysis. Participants who successfully withdraw from all immunosuppression will undergo a research biopsy at 52 weeks following drug discontinuation to determine whether they meet the primary efficacy outcome of operational tolerance. Participants determined to be operationally tolerant will be followed until 104 weeks following drug discontinuation and have a research biopsy at that time to confirm that they remain operationally tolerant. Participants who fail drug withdrawal after 52 weeks but before 104 weeks will be followed until week 104 or 12 weeks after resuming immunosuppression, whichever is longer. The research biopsy at week 104 will be optional for these participants. Participants who do not successfully withdraw from all immunosuppression will complete 104 weeks of High Intensity Safety Follow-up after failing immunosuppression withdrawal. \*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

Conditions

• Liver Transplant

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2019-03-29
• Primary completion: 2026-03-31
• Completion: 2027-04-06
• First posted: 2018-07-05
• Last updated: 2025-01-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study