What is the mechanism of action of this treatment?

Common treatments for liver transplant patients often involve immunosuppressive drugs like calcineurin inhibitors (e.g., tacrolimus), which inhibit T-cell activation, and mTOR inhibitors (e.g., sirolimus), which block cell proliferation. Cellular therapy, such as the use of regulatory T cells (Tregs), is being studied to facilitate immunosuppression withdrawal. Tregs help maintain immune tolerance by suppressing the immune response against the transplanted liver, potentially reducing the need for long-term immunosuppressive drugs. This is significant for liver transplant patients as it can lower the risk of infections, malignancies, and other side effects associated with chronic immunosuppression.

What side effects are associated with this type of intervention?

Common treatments for liver transplant include calcineurin inhibitors (cyclosporine and tacrolimus), corticosteroids, and antimetabolites (azathioprine and mycophenolate mofetil). Calcineurin inhibitors can cause nephrotoxicity, hypertension, and neurotoxicity. Corticosteroids are associated with weight gain, diabetes, osteoporosis, and increased infection risk. Antimetabolites can lead to bone marrow suppression, liver enzyme elevation, and gastrointestinal disturbances. These side effects are significant considerations in the management of liver transplant patients.

What prior FDA approvals exist?

FDA-approved treatments for liver transplantation primarily focus on immunosuppressive drugs to prevent organ rejection. Commonly used medications include calcineurin inhibitors (e.g., tacrolimus and cyclosporine), antiproliferative agents (e.g., mycophenolate mofetil), and corticosteroids. While these drugs are effective in preventing rejection, they require lifelong use and have significant side effects. Cellular therapies, such as the use of regulatory T cells (Tregs), are being studied to facilitate immunosuppression withdrawal by promoting immune tolerance. These innovative approaches aim to reduce or eliminate the need for long-term immunosuppressive drugs, potentially minimizing side effects and improving patient outcomes.

What other types of research exist?

Promising novel alternatives to cellular therapy for liver transplant patients include the use of regulatory T cells (Tregs) to facilitate immunosuppression withdrawal. This approach is currently being explored in clinical trials and aims to reduce the need for long-term immunosuppressive drugs by promoting immune tolerance. Additionally, advancements in biologic agents and personalized immunosuppressive regimens tailored to individual patient profiles are also being investigated as potential alternatives.

← Back to Search

Cell Therapy

Cellular Therapy for Liver Transplant Recipients (LITTMUS-MGH Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Positive Epstein-Barr virus (EBV) antibody test

Must not have

Known contraindication to cyclophosphamide or Mesna administration

CMV antibody negative recipients with a CMV antibody positive donor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up post-transplant through completion of study participation (up to 4.5 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a treatment using special cells to help liver transplant patients stop taking anti-rejection drugs. It targets liver transplant recipients and aims to help their immune systems accept the new liver naturally. Recent studies have shown benefits of combining these special cells with minimal medication to promote acceptance and potentially regeneration.

Who is the study for?

This trial is for liver transplant recipients with a positive Epstein-Barr virus test, who've completed treatment for HCV if applicable. Living donors must meet specific eligibility and manufacturing requirements. Contraception use is required, and vaccinations should be up to date. Exclusions include contraindications to certain drugs, chronic conditions that can't pause anticoagulation or immunosuppression, significant heart disease not cleared by a cardiologist, high-risk malignancies, and any factors affecting study compliance.

What is being tested?

The trial tests cellular therapy aiming to reduce the need for immunosuppression in liver transplant patients using everolimus (a drug), arTreg-CSB (modified T cells), leukapheresis (a procedure to collect white blood cells), cyclophosphamide and mesna (chemotherapy agents). It's an open-label study at MGH where participants are openly given these interventions without randomization.

What are the potential side effects?

Potential side effects may include immune system suppression leading to increased infection risk; reactions related to infusion of modified T cells; kidney issues from everolimus; nausea, bladder irritation from cyclophosphamide; and protective effects against hemorrhagic cystitis from mesna.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have severe liver disease and am on the list for a liver transplant.

Select...

I have tested positive for Epstein-Barr virus antibodies.

Select...

I am considering an organ from a deceased donor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am allergic or react badly to cyclophosphamide or Mesna.

Select...

I don't have CMV antibodies, but my donor does.

Select...

I have had a transplant that may need drugs to lower my immune response.

Select...

My liver disease is in its final stage due to an autoimmune condition.

Select...

I regularly use medications that affect my immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ post-transplant through completion of study participation (up to 4.5 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~post-transplant through completion of study participation (up to 4.5 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and post-transplant through completion of study participation (up to 4.5 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

Number of Operationally Tolerant Participants

+2 more

Secondary study objectives

Duration of Operational Tolerance

Number of AEs Attributed to Immunosuppression Withdrawal

Number of Adverse Events (AEs) Attributed to Cyclophosphamide

+15 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: arTreg-CSBExperimental Treatment5 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

everolimus

2005

Completed Phase 4

~1490

leukapheresis

2004

Completed Phase 3

~230

cyclophosphamide

1994

Completed Phase 3

~8140

mesna

1992

Completed Phase 3

~1420

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for liver transplant patients often involve immunosuppressive drugs like calcineurin inhibitors (e.g., tacrolimus), which inhibit T-cell activation, and mTOR inhibitors (e.g., sirolimus), which block cell proliferation. Cellular therapy, such as the use of regulatory T cells (Tregs), is being studied to facilitate immunosuppression withdrawal. Tregs help maintain immune tolerance by suppressing the immune response against the transplanted liver, potentially reducing the need for long-term immunosuppressive drugs. This is significant for liver transplant patients as it can lower the risk of infections, malignancies, and other side effects associated with chronic immunosuppression.