8 Participants Needed

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of administering mesenchymal stromal cells (MSCs) to kidney transplant recipients. These special cells may reduce the need for long-term use of anti-rejection drugs (immunosuppressants). The trial aims to determine if adding MSCs allows patients to gradually decrease or stop these drugs, which often cause serious side effects such as infections and cancer. Participants should be undergoing a kidney transplant from a donor who is not a perfect match and must have immunity to certain viruses like Epstein-Barr and Cytomegalovirus. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mesenchymal stromal cells (MSCs) have been tested in people before, and these studies indicate that MSCs are generally safe. In one study, patients received MSCs without any serious side effects. Another study found that repeated doses of donor MSCs did not cause any immediate negative effects.

This trial tests MSCs with various anti-rejection drugs. These drugs, such as Alemtuzumab, Belatacept, and Sirolimus, are already used in transplant patients to help prevent organ rejection. Since the FDA has approved these drugs for transplants, their safety is well-known when used correctly.

While the safety of using MSCs with these drugs is still under investigation, existing research suggests that MSCs are safe for humans at the doses previously tested.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about using Mesenchymal Stromal Cells (MSCs) for kidney transplant recipients because they offer a unique approach to preventing organ rejection. Unlike standard treatments, which typically involve a combination of immunosuppressants like Tacrolimus, Cyclosporine, and Mycophenolate Mofetil, MSCs work by modulating the immune system in a more targeted way, potentially reducing the side effects associated with long-term use of traditional immunosuppressants. The infusion of MSCs could enhance the body's acceptance of the new kidney while minimizing the risk of infection and other complications. This innovative method could represent a significant advancement in transplant medicine by improving outcomes and quality of life for patients.

What evidence suggests that this trial's treatments could be effective for kidney transplant recipients?

This trial will evaluate the use of mesenchymal stromal cells (MSCs) in kidney transplant patients. Participants will receive MSCs in varying dosages alongside anti-rejection drugs. Studies have shown that MSCs can be safely used in kidney transplant patients, and research suggests these cells might reduce the need for anti-rejection drugs, which can have harmful side effects. In earlier studies, MSCs helped adjust the immune system's response, similar to traditional treatments. Initial findings also suggest that donor MSCs could reduce the amount of strong medications like Tacrolimus needed by transplant patients, potentially leading to fewer side effects and a healthier outcome.23678

Who Is on the Research Team?

AD

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

Principal Investigator

Duke University Medical Center: Transplantation

Are You a Good Fit for This Trial?

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.
See 3 more

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.
See 5 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: MSCs 10^5 cells/kg+anti-rejection drugsExperimental Treatment7 Interventions
Group II: MSCs 10^4 cells/kg+anti-rejection drugsExperimental Treatment7 Interventions

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

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Approved in United States as Campath for:
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Approved in European Union as Lemtrada for:
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Approved in European Union as Campath for:

Find a Clinic Near You

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 profile image

David Simmons

PPD DEVELOPMENT, LP

Chief Executive Officer since 2012

BSc in Applied Science from Georgia Institute of Technology

Martina Flammer profile image

Martina Flammer

PPD DEVELOPMENT, LP

Chief Medical Officer since 2024

MD

PPD Development, LP

Industry Sponsor

PPD

Industry Sponsor

Trials
162
Recruited
36,600+
Dr. Austin Smith profile image

Dr. Austin Smith

PPD

Chief Medical Officer since 2020

Doctor of Medicine from the Royal College of Surgeons in Ireland

David Simmons profile image

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+

Published Research Related to This Trial

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

Citations

Autologous Mesenchymal Stromal Cells and Kidney ...Findings from this study in the two patients show that MSC infusion in kidney transplant recipients is feasible, allows enlargement of Treg in the peripheral ...
Donor-specific mesenchymal stem cell infusion in human ...We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) ...
Autologous Mesenchymal Stem Cells for Treatment of Chronic ...We found that AMR did not improve in any of the patients after treatment with MSCs. In addition, serious adverse events were observed in one ...
Mesenchymal Stem Cells in Solid Organ Transplantation ...The use of donor-derived MSCs in kidney transplant patients is safe and could provide potential benefits by reducing the dosage of Tacrolimus that is required ...
Induction therapy with mesenchymal stromal cells in kidney ...Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients.
Safety and Efficacy Endpoints for Mesenchymal Stromal ...Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study.
Safety of allogeneic bone marrow derived mesenchymal ...Mesenchymal stromal cells (MSC) may serve as an attractive therapy in renal transplantation due to their immunosuppressive and reparative ...
Allogeneic mesenchymal stromal cell therapy in kidney ...The Liège study aimed to evaluate the safety of a single infusion of third-party bone-marrow-derived MSCs in ten kidney transplant recipients ...
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