Liver Transplantation With Tregs at MGH

NCT03577431 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DAIT ITN073ST
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

alloantigen-reactive Tregs ( arTreg); immunosuppression; operational tolerance

Outcome Measures

Primary Outcomes (5)

• Number of Adverse Events (AEs) Attributed to the Investigational Product, arTreg-CSB

  The number of AEs attributed to the investigational product, arTreg-CSB. AEs will be attributed to arTreg-CSB when the AE is reported with possible or related attribution to arTreg-CSB.

  From arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Severity of Adverse Events (AEs) Attributed to the Investigational Product, arTreg-CSB

  Assessment of the intensity of AEs attributed to the investigational product, arTreg-CSB. AEs will be attributed to arTreg-CSB when the AE is reported with possible or related attribution to arTreg-CSB. Grading according to the NCI Common Terminology Criteria for Adverse Events \[NCI-CTCAE version 4.03\].

  From arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Number of Adverse Events (AEs) Attributed to the Investigational Product's Supportive Regimen (Leukapheresis, Cyclophosphamide and Mesna)

  The number of AEs attributed to the investigational product's supportive regimen (leukapheresis, cyclophosphamide, and mesna). AEs will be attributed to the supportive regimen when the AE is reported with possible or related attribution to leukapheresis, cyclophosphamide, or mesna.

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Severity of Adverse Events (AEs) Attributed to the Investigational Product's Supportive Regimen (Leukapheresis, Cyclophosphamide and Mesna)

  Assessment of the intensity of AEs attributed to the investigational product's supportive regimen (e.g., leukapheresis, cyclophosphamide, and mesna). AEs will be attributed to the supportive regimen when the AE is reported with possible or related attribution to leukapheresis, cyclophosphamide, or mesna. Assessment of the intensity of AEs will be graded according to the NCI Common Terminology Criteria for Adverse Events \[NCI-CTCAE version 4.03\].

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Number of Operationally Tolerant Participants

  Operational tolerance is defined as: * Discontinuation of immunosuppression for 52 weeks, * Alanine aminotransferase (ALT) ≤ 50 U/L, and * A liver biopsy at 52 weeks (±4 weeks) after the last dose of immunosuppression that meets the criteria noted per protocol. * Liver histology will be assessed by central pathology.

  52 weeks (±4 weeks) after the last dose of immunosuppression

Secondary Outcomes (18)

• Number of Adverse Events (AEs) Attributed to Leukapheresis

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Severity of Adverse Events (AEs) Attributed to Leukapheresis

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Number of Adverse Events (AEs) Attributed to Cyclophosphamide

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Severity of Adverse Events (AEs) Attributed to Cyclophosphamide

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

• Number of Adverse Events (AEs) Attributed to Mesna

  From ≤3 days prior to arTreg-CSB infusion through completion of study participation (Up to 4.5 years)

Study Arms (1)

arTreg-CSB

EXPERIMENTAL

arTreg CSB: alloantigen-reactive T regulatory cells costimulatory blockade per protocol. The investigational product is donor alloantigen-specific T regulatory cells (arTreg-CSB). Supportive regimen for receipt of arTregs-CSB includes everolimus, leukapheresis, cyclophosphamide, and mesna. Participants will receive a single dose of Treg product (arTreg-CSB). The target dose is 2.5 to 125 x 10\^6 total cells. arTreg-CSB will be administered as a single peripheral intravenous (IV) infusion over approximately 15 to 30 minutes. Note: Participants who receive at least the minimum Treg product (arTreg-CSB) dose of 1 to \< 2.5 x 10\^6 cells will be included in intent-to-treat analysis.

Biological: arTreg-CSB; Procedure: leukapheresis; Drug: cyclophosphamide; Drug: mesna; Drug: everolimus

Interventions

arTreg-CSB BIOLOGICAL

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.

Also known as: donor alloantigen specific regulatory T cells, CD4+CD25+CD127[lo] Treg cells

arTreg-CSB

leukapheresis PROCEDURE

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.

Also known as: apheresis

arTreg-CSB

cyclophosphamide DRUG

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

Also known as: Cytoxan®

arTreg-CSB

mesna DRUG

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

Also known as: Mesnex®

arTreg-CSB

everolimus DRUG

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.

Also known as: EVR, Afinitor®, Zortress®

arTreg-CSB

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility:
• Recipient:
• Individuals must meet all of the following criteria to be eligible for this study:
• Able to understand and provide informed consent
• End-stage liver disease and listed for a living or deceased-donor primary solitary liver transplant
• Agreement to use contraception
• Positive Epstein-Barr virus (EBV) antibody test and
• In the absence of contraindication, vaccinations must be up to date per the DAIT Guidance for Patients in Transplant Trials (Refer to the Manual of Procedures)
• Living Donor:
• Living donors must meet all of the following criteria to be eligible for this study:
• Able to understand and provide informed consent
• Meets site-specific clinical donor eligibility requirements
• Meets donor eligibility manufacturing requirements within 7 days prior to blood collection for manufacturing and
• Willingness to donate appropriate biologic samples.
• Deceased Donor:

You may not qualify if:

• Recipient:
• Individuals who meet any of the following criteria will not be eligible for this study:
• History of previous organ, tissue or cell transplant requiring or potentially requiring immunosuppression
• For cytomegalovirus (CMV) antibody negative recipients, a (CMV) antibody positive donor
• Known contraindication to cyclophosphamide or Mesna administration
• Serologic evidence of human immunodeficiency virus (HIV)-1/2 infection
• The need for chronic anti-coagulation that cannot be safely discontinued for a minimum of 1 week to safely perform a liver biopsy
• End stage liver disease secondary to autoimmune etiology (autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis) or other contraindications to drug withdrawal
• Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
• Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may interfere with study compliance
• Past or current medical problems, treatments or findings that are not listed above, which, in the opinion of the investigator, may:
• \-- pose additional risks from participation in the study,
• interfere with the candidate's ability to comply with study requirements, or
• impact the quality or interpretation of the data obtained from the study.
• History of malignancy with a risk of recurrence judged by the investigator to be \>1%, except for:

Sponsors & Collaborators

• Immune Tolerance Network (ITN): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Massachusetts General Hospital: Transplantation

Boston, Massachusetts, 02114, United States

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Immune Tolerance Network web site

MeSH Terms

Interventions

Leukapheresis; Blood Component Removal; Cyclophosphamide; Mesna; Everolimus

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Sirolimus; Macrolides; Lactones

Study Officials

• James F. Markmann, MD, PhD

  University of Pennsylvania Medical Center: Transplantation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 5, 2018
• Study Start: March 29, 2019
• Primary Completion: February 6, 2026
• Study Completion (Estimated): April 6, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: The aim is to share data available to the public within 24 months upon completion of the study.
• Access Criteria: ImmPort public data access.

Locations

US (1)