Cellular Therapy for Liver Transplant Recipients

(LITTMUS-MGH Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Glucocorticoids, Immunosuppressives

Disqualifiers: HIV, Autoimmune liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 53

Duration: 1 day

9 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive drugs or systemic glucocorticoids, you may not be eligible to participate.

What data supports the effectiveness of the treatment arTreg-CSB for liver transplant recipients?

Research shows that regulatory T cells (Tregs) can be expanded and used in liver transplant settings to promote transplant tolerance, even in patients with liver failure or on immunosuppressive therapy. This suggests that treatments involving Tregs, like arTreg-CSB, may help improve outcomes for liver transplant recipients. ^{1 2 3 4 5}

Is cellular therapy safe for liver transplant recipients?

Research shows that cellular therapies, including mesenchymal stromal cells and regulatory T cells, have been generally safe for liver transplant patients. Studies found no significant adverse events related to these treatments, suggesting they are safe for human use in this context. ^{6 7 8 9 10}

How is the treatment arTreg-CSB different from other treatments for liver transplant recipients?

The treatment arTreg-CSB is unique because it involves using regulatory T cells, which are a type of immune cell, to help liver transplant recipients potentially reduce or eliminate the need for long-term immunosuppressive drugs. This approach aims to induce 'operational tolerance,' allowing the body to accept the transplanted liver without ongoing medication to suppress the immune system. ^{2 6 11 12 13}

Research Team

James F. Markmann, MD, PhD

Principal Investigator

University of Pennsylvania Medical Center: Transplantation

Eligibility Criteria

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.

Inclusion Criteria

Recipient:

I understand the study and can give my consent.

Agreement to use contraception

Exclusion Criteria

I am allergic or react badly to cyclophosphamide or Mesna.

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

Factors potentially hampering compliance with the study protocol and follow-up visit schedule

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Treg product (arTreg-CSB) via IV infusion

1 day

1 visit (in-person)

Immunosuppression Withdrawal

Participants attempt to withdraw from all immunosuppression over 52 weeks

52 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including research biopsies at 52 and 104 weeks

104 weeks

Research biopsies at 52 and 104 weeks

Treatment Details

Interventions

• arTreg-CSB
• Cyclophosphamide
• Everolimus
• Mesna

Trial Overview 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.

Participant Groups

Group I: arTreg-CSB Experimental Treatment 5 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.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Immune Tolerance Network (ITN)

Collaborator

Trials

68

Recruited

7,900+

References

1. China pubmed.ncbi.nlm.nih.gov

[Granulocyte colony-stimulating factor-mobilized autologous bone marrow stem cells promote the liver regeneration of partial liver transplant: an experiment with rats]. [2011]

2. England pubmed.ncbi.nlm.nih.gov

Application of liver stem cells for cell therapy. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Ex vivo generation of regulatory T cells from liver transplant recipients using costimulation blockade. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Autologous mobilized peripheral blood CD34(+) cell infusion in non-viral decompensated liver cirrhosis. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

Therapeutic liver repopulation for the treatment of metabolic liver diseases. [2012]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cell-Mediated Therapies to Facilitate Operational Tolerance in Liver Transplantation. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Third-party bone marrow-derived mesenchymal stromal cell infusion before liver transplantation: A randomized controlled trial. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Hepatic progenitors and strategies for liver cell therapies. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Mobilization of host stem cells enables long-term liver transplant acceptance in a strongly rejecting rat strain combination. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Stem cells in liver failure. [2022]