NCT02188719

Donor-Alloantigen-Reactive Regulatory T Cell (darTregs) in Liver Transplantation

Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Liver Transplantation (RTB-002)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 21 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is look at the safety of: * Taking a specific combination of immunosuppressant drugs after liver transplantation * Receiving one of three different doses of donor-alloantigen-reactive regulatory T cells (darTregs) while taking this specific combination of drugs

Detailed description

After liver transplantation, immunosuppressants must be taken every day to prevent the body from injuring the transplanted liver by a process called rejection. People who take these drugs may experience side effects. Studies show that some of body's cells, called T regulatory cells (Tregs), may play a part in accepting the transplanted liver. The investigators are learning about whether scientists can take Tregs from the blood of a liver transplant recipient and teach them to protect the transplanted liver from rejection. In the laboratory, the recipient Tregs are exposed to cells from the liver donor. Research data suggests that giving these "donor reactive" Tregs back to the transplant recipient might allow a liver transplant recipient to take lower doses of immunosuppressants, or perhaps to stop them altogether, without rejecting the liver.

Conditions

• Liver Transplantation

Interventions

Type	Name	Description
BIOLOGICAL	Anti-Thymocyte Globulin - Rabbit	Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects will be given a dose range of 3.0-4.5 mg/kg total, in divided doses of 1.5 mg/kg/day. Subjects who meet eligibility criteria for Thymoglobulin® administration will be given 1.5 mg/kg intravenously (IV) on post-operative day 3, within 72 hours of transplantation. Additional doses of 1.5 mg/kg IV will be administered until CD3 count is \<50/mm\^3 or when the maximal dose of 4.5/mg/kg has been given.
BIOLOGICAL	darTreg Infusion	A single dose darTreg infusion (Cohorts 2 - 4) will be received as per protocol.
DRUG	Everolimus	Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Subjects meeting eligibility criteria for Treg-supportive IS regimen will begin EVR no sooner than 30 days after liver transplantation and no later than 44 days after transplantation; with target trough levels of 6-8 μg/L.EVR target trough levels will be further reduced to 4-6 μg/L 24 - 26 weeks after transplantation.
DRUG	Tacrolimus	Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Between 30 and 44 days following transplant: Subjects who are not eliminated by Exclusion Criteria C1 (Protocol Section 14.3.1) will proceed in the study and receive either TAC-based or EVR- based IS, based on eligibility Criteria C2 (Section 4.3.4 ) * TAC-based IS: reduce TAC trough level to 3-8 μg/dL; continue MMF * EVR-based IS: reduce TAC trough level to 3-8 μg/dL; EVR target trough level of 6-8 μg/dL; decrease then discontinue MMF
DRUG	Mycophenolate mofetil	Liver transplantation/Treg-supportive immunosuppression (IS) treatment. 1000 mg total daily dose. MMF will be initiated within 24 hours of transplantation. MMF must be discontinued as soon as target EVR trough levels have been achieved.
DRUG	Prednisone	Liver transplantation/Treg-supportive immunosuppression (IS) treatment. Solumedrol 500 mg will be given IV on the day of transplantation. Additional Solumedrol will be prescribed according to site-specific standard of care. Oral prednisone should be initiated once oral medication is tolerated.
DRUG	Acetaminophen	Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 650mg of acetaminophen will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
DRUG	Diphenhydramine	Pre-medication for single dose darTreg infusion (Cohorts 2 - 4). 25-50mg of diphenhydramine will be administered intravenously or by mouth 30-60 minutes prior to the darTreg infusion.
DRUG	Anti-Infective Prophylaxis	Intravenous ganciclovir and/or oral Valcyte will be administered for the prophylaxis of cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) for at least six months after liver transplantation.
PROCEDURE	Leukapheresis	Leukapheresis is necessary to ensure collection of adequate numbers of autologous Tregs to support ex vivo expansion of darTregs for infusion after liver transplantation. Participants enrolled in Cohorts 3 and 4 will undergo leukapheresis. Participants enrolled in Cohort 2 will have either whole blood collection or leukapheresis for the purpose of isolating autologous Tregs for later manufacture. If a cohort 2 subject has a hemoglobin level \>/=10.5 gm/dL, he or she will undergo phlebotomy. If the patient has a hemoglobin level \</=10.5 gm/dL and remains eligible for the study, the patient will undergo leukapheresis.
PROCEDURE	Blood draws	Blood draws are necessary to carefully and frequently evaluate allograft function after liver transplantation and treatment with Treg-supportive IS as well as after darTreg infusion. Peripheral blood samples will be collected and analyzed per protocol throughout subject participation in this study.
PROCEDURE	Liver biopsies	Subjects will have a liver biopsy for this study 12-14 weeks after transplantation. For subjects receiving darTregs, a second biopsy will be performed 7-10 days after darTregs infusion.
PROCEDURE	Liver transplantation	Inclusion in this trial is in the setting of subjects defined as having end-stage liver disease and listed for primary solitary liver transplant.

Timeline

• Start date: 2014-12-17
• Primary completion: 2019-06-18
• Completion: 2019-06-18
• First posted: 2014-07-14
• Last updated: 2020-09-22
• Results posted: 2020-07-20

Locations

3 sites across 1 country: United States