Mesenchymal Stromal Cells + Immunosuppressants for Kidney Transplant Recipients

(TEACH Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Prednisone, Cyclosporine, others

Disqualifiers: Immunodeficiency, Hepatitis, Malignancy, others

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

Compensation: Varies

Number of Visits: 12

8 Participants Needed

Trial Summary

What is the purpose of this trial?

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine if: * it is safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and * the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs can allow a kidney transplant recipient to slowly reduce and/or then completely stop all anti-rejection drugs, without rejection of their kidney (renal) allograft, a process called "immunosuppression withdrawal".

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it aims to help participants reduce or stop anti-rejection drugs. You should discuss your current medications with the trial team to understand any specific requirements.

What data supports the effectiveness of the treatment Mesenchymal Stromal Cells + Immunosuppressants for Kidney Transplant Recipients?

Research shows that using Alemtuzumab (Campath-1H) with sirolimus for kidney transplants resulted in high patient survival rates (100%) and good graft survival (96%) over three years, with many patients successfully maintained on reduced immunosuppressive therapy without serious infections or cancer. ^{1 2 3 4 5}

Is the combination of mesenchymal stromal cells and immunosuppressants safe for kidney transplant recipients?

The combination of Campath-1H (alemtuzumab) and sirolimus showed good patient and graft survival rates with no serious infections and minimal cancer risk over three years. Belatacept, when used with other immunosuppressants, has a good safety profile but is not recommended for patients with certain viral infections due to increased cancer risk. ^{1 6 7 8 9}

What makes the treatment with Mesenchymal Stromal Cells and immunosuppressants unique for kidney transplant recipients?

This treatment is unique because it combines Mesenchymal Stromal Cells with a range of immunosuppressants, including alemtuzumab, which allows for the possibility of reducing or avoiding the use of traditional steroids and calcineurin inhibitors, potentially minimizing side effects and improving long-term outcomes. ^{1 3 4 10 11}

Research Team

Allan D. Kirk, M.D., Ph.D.

Principal Investigator

Duke University Medical Center: Transplantation

Eligibility Criteria

This trial is for adults needing a kidney transplant from a living donor who's not an exact tissue match. They must have immunity to Epstein-Barr and Cytomegalovirus (if the donor has it), meet organ sharing network criteria, and agree to use effective birth control. People with immune deficiencies, certain cancers, high-risk kidney diseases, or recent immunosuppressive drugs can't join.

Inclusion Criteria

Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing

I have had CMV before, and my donor is CMV positive.

I am not pregnant and agree to use effective birth control during and for 18 months after treatment.

Exclusion Criteria

Recipient must not have active autoimmune disease, uncompensated heart failure, active severe infection, recent use of investigational drugs, medical conditions incompatible with trial participation, or unwillingness to comply with protocol monitoring and therapy

I do not have any immune deficiency or hepatitis.

I haven't had cancer, except for certain skin cancers or cervical cancer, in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive induction therapy with alemtuzumab followed by maintenance therapy with sirolimus and belatacept

6 weeks

MSC Infusion

Participants receive 12 infusions of donor-derived MSCs starting on Day 42 post-transplant and every 4 weeks starting on Day 56 post-transplant

48 weeks

12 visits (in-person)

Immunosuppression Withdrawal

Participants are evaluated for eligibility for sirolimus withdrawal between week 52 and week 104 post-transplant

52 weeks

Follow-up

Participants who successfully complete Immunosuppression Withdrawal undergo 24 weeks of high frequency follow up followed by 132 weeks of standard follow up

156 weeks

Treatment Details

Interventions

• Alemtuzumab
• Belatacept
• Donor-derived Mesenchymal Stromal Cells
• Mycophenolate Acid
• Mycophenolate Mofetil
• Prednisone
• Sirolimus

Trial Overview The study tests if mesenchymal stromal cells (MSCs) are safe for kidney recipients and if they help reduce or stop anti-rejection drugs without organ rejection. It involves multiple anti-rejection medications like alemtuzumab, belatacept, sirolimus, mycophenolate acid/mofetil, prednisone.

Participant Groups

Group I: MSCs 10^5 cells/kg+anti-rejection drugs Experimental Treatment 7 Interventions

If the first 3 infusions of 10\^4 donor-derived Mesenchymal Stromal Cells (MSCs) cells/kg are well tolerated, this cohort of 2 participants will receive 12 infusions of 10\^5 cells/kg every 4-weeks.

Group II: MSCs 10^4 cells/kg+anti-rejection drugs Experimental Treatment 7 Interventions

The first dosing cohort of 2 participants will receive 12 infusions of 10\^4 donor-derived Mesenchymal Stromal Cells (MSCs) cells/kg every 4-weeks.

Alemtuzumab is already approved in United States, European Union for the following indications:

Approved in United States as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Approved in European Union as Lemtrada for:

• Multiple sclerosis

Approved in European Union as Campath for:

• Chronic lymphocytic leukemia

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

PPD DEVELOPMENT, LP

Industry Sponsor

Trials

167

Recruited

38,000+

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD

Industry Sponsor

Trials

162

Recruited

36,600+

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons

PPD

Chief Executive Officer since 2012

Bachelor’s degree in Applied Mathematics and Industrial Management from Carnegie Mellon University

Immune Tolerance Network (ITN)

Collaborator

Trials

68

Recruited

7,900+

Rho Federal Systems Division, Inc.

Industry Sponsor

Trials

44

Recruited

15,000+

Findings from Research

Belatacept is a newly approved immunosuppressive therapy for kidney transplant recipients that has been shown to improve long-term graft function and is effective in preventing kidney allograft rejection, based on data from Phase II and III clinical trials.

Unlike traditional therapies, belatacept may reduce the risk of chronic side effects associated with calcineurin inhibitors and steroids, making it a promising option for long-term immunosuppression, although it is contraindicated in patients with unknown Epstein-Barr virus serostatus due to increased risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept utilization recommendations: an expert position. Grinyó, JM., Budde, K., Citterio, F., et al.[2015]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

Alemtuzumab induction therapy in kidney transplantation significantly reduces the risk of biopsy-proven acute rejection (BPAR) compared to interleukin-2 receptor antibodies (IL-2RAs), with a relative risk of 0.54 based on a systematic review of 10 randomized controlled trials involving 1223 patients.

There was no significant difference in the risk of BPAR when comparing alemtuzumab to rabbit antithymocyte globulin (rATG), and other outcomes like graft loss and patient death were similar across induction methods, suggesting that safety and cost may guide the choice of induction therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis. Morgan, RD., O'Callaghan, JM., Knight, SR., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. [2017]

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

T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Novel immunosuppressive agents in kidney transplantation. [2019]

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

Alemtuzumab induction in renal transplantation permits safe steroid avoidance with tacrolimus monotherapy: a randomized controlled trial. [2021]

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

Kidney transplantation with minimized maintenance: alemtuzumab induction with tacrolimus monotherapy--an open label, randomized trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Belatacept utilization recommendations: an expert position. [2015]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. [2020]

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

Belatacept: a new biologic and its role in kidney transplantation. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Immunosuppressive minimization with mTOR inhibitors and belatacept. [2021]

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

The use of Campath-1H as induction therapy in renal transplantation: preliminary results. [2021]

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

Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis. [2018]