Liver Transplantation With Tregs at MGH

• Status: Recruiting
• Trial end date: 2026-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Treatments: Cyclophosphamide; Everolimus; Mesna; Sirolimus

Criteria

Inclusion Criteria:

Eligibility:

Recipient:

• Individuals must meet all of the following criteria to be eligible for this study:

1. Able to understand and provide informed consent

2. End-stage liver disease and listed for a living or deceased-donor primary solitary liver transplant

3. Agreement to use contraception

4. Negative test for hepatitis C infection by hepatitis C virus (HCV) PCR RNA

5. For candidates with a history of HCV, completed treatment for HCV

6. Positive Epstein-Barr virus (EBV) antibody test and

7. Immunizations are up-to-date based on the Advisory Committee on Immunization Practices (ACIP) recommendations, unless the investigator determines that administering a recommended immunization is not in the participant's best interest.

Living Donor:

• Living donors must meet all of the following criteria to be eligible for this study:

1. Able to understand and provide informed consent

2. Meets site-specific clinical donor eligibility requirements

3. Meets donor eligibility manufacturing requirements within 7 days prior to blood collection for manufacturing and

4. Willingness to donate appropriate biologic samples.

Deceased Donor:

Deceased donors must meet the following criteria for their recipients to be eligible for this study:

1. Meets site-specific clinical donor eligibility requirements and

2. Meets donor eligibility manufacturing requirements.

Note:

• There are several stages to this study.

• Eligibility is evaluated at many time points during the study to assess whether a participant is safe to proceed to the next study stage.

Exclusion Criteria:

Recipient:

-Individuals who meet any of the following criteria will not be eligible for this study:

1. History of previous organ, tissue or cell transplant requiring or potentially requiring immunosuppression

2. For cytomegalovirus (CMV) antibody negative recipients, a (CMV) antibody positive donor

3. Known contraindication to cyclophosphamide or Mesna administration

4. Serologic evidence of human immunodeficiency virus (HIV)-1/2 infection

5. The need for chronic anti-coagulation that cannot be safely discontinued for a minimum of 1 week to safely perform a liver biopsy

6. End stage liver disease secondary to autoimmune etiology (autoimmune hepatitis, primary biliary cirrhosis, or primary sclerosing cholangitis) or other contraindications to drug withdrawal

7. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule

8. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may interfere with study compliance

9. History of ischemic heart disease requiring revascularization, history of or current treatment for dysrhythmia, or evidence of congestive heart failure, unless cleared by a cardiologist

10. 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.

11. History of malignancy with a risk of recurrence judged by the investigator to be >1%, except for:

• hepatocellular carcinoma,

• completely treated in-situ cervical carcinoma, or

• completely treated basal cell carcinoma.

12. Chronic use of systemic glucocorticoids or other immunosuppressives, or biologic immunomodulators.

Living Donor:

Living donors who meet the following criteria will not be eligible for this study:

1. Any condition that, in the opinion of the investigator, may pose additional risks from participation in the study, may:

• interfere with the participant's ability to comply with study requirements or

• impact the quality or interpretation of the data obtained from the study.

Deceased Donor:

Recipients of livers from deceased donors who meet the following criteria are ineligible for this study:

1. Any condition that, in the opinion of the investigator, may pose additional risks or may impact the quality or interpretation of the data obtained from the study.