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

Trial Summary

What is the purpose of this trial?

This trial tests if giving special cells from a kidney donor can help patients accept a new kidney without needing long-term medication. It targets patients receiving a kidney from a related donor. The treatment involves preparing the body and mixing donor and patient immune cells to prevent rejection.

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.

What data supports the effectiveness of the treatment Donor Stem Cells for renal disease?

Research shows that using donor stem cells, specifically hematopoietic stem cells from bone marrow, can help kidney transplant patients accept the new organ without long-term rejection. This approach has been successful in both animal studies and human trials, suggesting it may improve the long-term success of kidney transplants by promoting immune tolerance. ^{1 2 3 4 5}

Is the use of donor stem cells for immune tolerance in kidney transplants safe?

Research shows that using donor stem cells in kidney transplants has been generally safe, with no adverse effects observed in some trials. Patients tolerated the treatment well, and no serious complications like rejection or infections were reported. ^{1 4 6 7 8}

How does the treatment for Stem Cell-Induced Immune Tolerance for Renal Disease differ from other treatments?

This treatment is unique because it uses hematopoietic stem cells (special cells that can develop into different types of blood cells) to create immune tolerance, reducing the need for long-term immunosuppressive drugs that can have serious side effects. It aims to achieve a state called 'chimerism', where the patient's immune system accepts the transplanted kidney as its own, potentially improving long-term transplant success. ^{1 2 3 5 9}

Research Team

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

Infusion of donor-derived hematopoietic stem cells in organ transplantation: clinical data. [2004]

2. Australia pubmed.ncbi.nlm.nih.gov

Clinical trials for renal allograft tolerance induction through combined hematopoietic stem cell transplantation: A narrative review. [2023]

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

The quest for transplantation tolerance: have we finally sipped from the cup? [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001). [2021]

8. England pubmed.ncbi.nlm.nih.gov

Kidney transplant tolerance associated with remote autologous mesenchymal stromal cell administration. [2021]

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

Chimerism-Based Tolerance to Kidney Allografts in Humans: Novel Insights and Future Perspectives. [2022]