Stem Cell-Induced Immune Tolerance for Renal Disease

Recruiting at 1 trial location

Overseen By Asha Shori, CCRP

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether donor stem cells can help kidney transplant patients stop taking immunosuppressive drugs, which usually prevent the body from rejecting the new kidney. Researchers focus on patients receiving a kidney from a living donor who is a close genetic match. This trial suits those needing a kidney transplant with a relative or closely matched donor available. Participants should not have allergies to certain medications or serious infections like HIV or Hepatitis. The goal is to ease life after a transplant by reducing the need for lifelong medication. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that donor stem cells are likely to be safe for humans?

Research has shown that donor stem cells have been safe in past studies. In liver transplants, using these cells in various ways proved safe, with no major safety issues reported. This suggests that donor stem cells are generally well-tolerated in transplant situations.

However, another study using a person's own stem cells reported some serious side effects. Although this differs from using donor stem cells, it underscores the need for careful monitoring.

For kidney transplants, studies on methods to help the body accept the new organ, including the use of donor stem cells, have shown promise. This suggests the body might accept the new organ more effectively with fewer complications.

Overall, while early results are promising, staying informed and consulting medical professionals about any concerns before joining a trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for kidney transplantation, which often involves lifelong immunosuppressive drugs to prevent organ rejection, this new approach uses donor stem cells to induce immune tolerance. This means that the recipient's immune system could potentially accept the new kidney without needing ongoing medication to suppress it. Researchers are excited because this method could significantly reduce the side effects associated with immunosuppressive therapy and improve the overall quality of life for transplant recipients by creating a more natural acceptance of the donor organ.

What evidence suggests that donor stem cells might be an effective treatment for renal disease?

Research has shown that using donor stem cells in kidney transplants can help the body accept the new kidney more easily. In this trial, participants will receive donor stem cells alongside their kidney transplant to induce immune tolerance. Previous studies found that patients who received donor stem cells with their kidney transplant needed fewer strong drugs to prevent their immune system from attacking the new organ. These patients achieved "immune tolerance," meaning their bodies accepted the new kidney without problems. Specifically, one study found that this method helped kidney transplants function well for over two years without major issues. Overall, using donor stem cells has been shown to be generally safe and effective in helping kidney transplants last longer. ^{5 6 7 8 9}

Who Is on the Research Team?

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

Adults aged 18-60 needing a kidney transplant with a related living donor who's a partial genetic match, or an unrelated donor matching at least two HLA antigens. Participants must consent to the study and use reliable contraception post-transplant. Exclusions include pregnant/nursing women, cancer history (except certain skin cancers), low blood counts, high antibody levels against donors, prior transplants, rabbit protein allergies, and certain infections.

Inclusion Criteria

My blood type matches the donor's.

I am not allergic to rabbit ATG or radiation treatments.

I am between 18 and 60 years old and have a matching living donor for a transplant.

Exclusion Criteria

Seronegative for Epstein-Barr virus if donor is seropositive

Leukopenia (white blood cell count < 3000/mm3) or thrombocytopenia (platelet count < 100,000/mm3)

My body has a high level of antibodies against a transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Recipients receive a conditioning regimen composed of low dose radiation to the lymphoid tissue and anti-thymocyte globulin at the time of transplant

At the time of transplant

Stem Cell Infusion

Infusion of purified stem cell and T-cell from kidney donors to achieve mixed chimerism

2 weeks after transplant

Immunosuppressive Tapering

Gradual decrease and potential withdrawal of immunosuppressive medication if criteria are met

Up to 1.5 years

Follow-up

Participants are monitored for safety, effectiveness, and long-term freedom from immunosuppressive drugs

5 years and indefinitely if possible

What Are the Treatments Tested in This Trial?

Interventions

• Donor Stem Cells

Trial Overview The trial is testing if stem cells from the kidney donor can help change the recipient's immune system so that they might eventually stop taking anti-rejection drugs. This involves patients receiving their relative's kidney plus stem cells to see if their body will accept the new organ without long-term medication.

How Is the Trial Designed?

Group I: Immune Tolerance, Kidney transplantation Experimental Treatment 1 Intervention

Induction of immune tolerance in Haplotype matched living donor kidney transplantation.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Everett Meyer

Lead Sponsor

Trials

5

Recruited

150+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Recent advancements in achieving hematopoietic chimerism could improve the chances of developing immunological tolerance in kidney transplant recipients.

This approach may lead to better transplant outcomes by reducing the risk of organ rejection, although specific study details and participant numbers are not provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The quest for transplantation tolerance: have we finally sipped from the cup? Markmann, JF., Kawai, T.[2021]

Inducing immune tolerance in kidney transplantation can potentially eliminate the need for long-term immunosuppression, which is crucial for improving long-term outcomes and reducing toxicity associated with current treatments.

Clinical protocols using chimerism induction have successfully achieved immune tolerance in a significant number of HLA-mismatched donor-recipient pairs, although differences in tolerance mechanisms between animal models and humans highlight the need for further research to optimize these approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives. Podestà, MA., Sykes, M.[2022]

This study reports the successful induction of immunological tolerance in three patients who received a kidney and hematopoietic stem cell transplant from HLA-identical siblings, with all patients remaining off immunosuppression for up to 4 years without rejection or graft-versus-host disease.

The approach demonstrated not only the feasibility of achieving tolerance but also maintained the patients' immune responses, as evidenced by their strong reactions to the mRNA COVID-19 vaccine, indicating a preserved ability to respond to infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings. Fehr, T., Hübel, K., de Rougemont, O., et al.[2022]

Injecting donor-derived CD34+ bone marrow stem cells into kidney transplant recipients can help induce tolerance, which is a key goal in transplantation.

In a clinical trial, the infusion of these cells was found to be safe and well tolerated, with no adverse effects reported, highlighting their potential for improving transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusion of donor-derived hematopoietic stem cells in organ transplantation: clinical data. De Pauw, L., Toungouz, M., Goldman, M.[2004]

Hematopoietic stem cells (HSCs) have the potential to promote immune tolerance for transplanted organs and tissues, which could help prevent rejection and improve outcomes in organ transplantation.

Recent studies have shown success in achieving durable mixed chimerism and organ allograft tolerance without causing graft-versus-host disease, indicating a promising pathway for treating various human diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism. Gibbons, C., Sykes, M.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7723571/

Tolerance induction with donor hematopoietic stem cell ... Our immune tolerance induction protocol, which used DHSC infusion and TLI, achieved low dose immunosuppression with long-term stable kidney allograft survival ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1600613525000735

Induction of immune tolerance in living related human ... Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than 2 years with no death, graft loss ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00183248

Using Donor Stem Cells and Alemtuzumab to Prevent ... This study will evaluate the safety and effectiveness of an antirejection regimen including alemtuzumab and other immunosuppressive medications and donor bone ...

4. withpower.com withpower.com/trial/phase-1-6-2010-0979f

Stem Cell-Induced Immune Tolerance for Renal Disease Research shows that using donor stem cells in kidney transplants has been generally safe, with no adverse effects observed in some trials. Patients tolerated ...

5. kidneyregistry.com kidneyregistry.com/wp-content/uploads/2024/12/Kriger_Paper.php_.pdf

Immune tolerance via FCR001 cell therapy compared with ... In conclusion, RWE demonstrated that KTx combined with non-myeloablative condi- tioning and FCR001 resulting in superior kidney function without ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5504958/

Safety and Tolerance of Donor-Derived Mesenchymal ... Preliminary reports showed that systemic and intraportal infusions of allogeneic MSCs after deceased and living-donor liver transplantation were safe and well ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0955470X23000460

Review article Hematopoietic cell-based and non- ... The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism- ...

8. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10772/full

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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8222735/

Harnessing Mechanisms of Immune Tolerance to Improve ... Chimerism that persists for at least six months after transplant is associated with improved kidney graft tolerance and effective immune response to infection ...