NCT03654040

Liver Transplantation With Tregs at UCSF

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (actual)
• 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. Eligible participants will receive a single dose of Treg product (arTreg). The target dose is at least 90 to 500 x 10\^6 total cells. Participants who successfully withdraw from all immunosuppression (IS) will undergo a research biopsy at 52 weeks following IS 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 IS discontinuation. 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. Participants who do not successfully withdraw from all IS 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	Eligible participants will receive a single dose of Treg product (arTreg). The target dose is at least 90 x 10\^6 total cells. Method of receipt: peripheral intravenous (IV) infusion, administered over 20 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 on Day -3 (-1 day) prior to Treg product (arTreg) IV infusion.
DRUG	cyclophosphamide	40 mg/kg administered intravenously (IV) following leukapheresis and between 1 to 3 days prior to Treg product (arTreg) infusion, per institutional standard of care.
DRUG	mesna	Mesna is administered: * Intravenously to inhibit hemorrhagic cystitis induced by cyclophosphamide, and * In conjunction with the cyclophosphamide, per institutional practice with CTX.
DRUG	everolimus	EVR is approved for prophylaxis of allograft rejection in adults receiving a liver transplant. Per protocol: Post transplantation, subject will initially receive standard IS with tacrolimus (TAC),plus a mycophenolate product and/or steroids.Subsequently, evaluation for eligibility to be converted to EVR-based IS regimen will occur and, when applicable, proceed. Once the optimal EVR trough level is achieved,TAC dose will be reduced. When target EVR and TAC levels are maintained over two consecutive measurements, ALT liver function test (LFT) is ≤50 U/L, GGT LFT is ≤ the upper limit of normal or ≤ 1.5 times the baseline GGT, subject will be considered successfully converted to EVR-based IS regimen. EVR doses will be administered/monitored/adjusted over time.

Timeline

• Start date: 2021-04-22
• Primary completion: 2023-03-06
• Completion: 2023-03-06
• First posted: 2018-08-31
• Last updated: 2024-04-23
• Results posted: 2024-04-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study