Kidney + Marrow Cell Transplant for Immune Tolerance

Overseen By Stephan Busque, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Disqualifiers: Malignancy, HIV, Hepatitis, Infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion and kidney transplantation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an active infection and are taking medication for it, you may not be eligible to participate.

What data supports the effectiveness of the treatment Combined Deceased Donor Kidney and Hematopoietic Cell Transplants?

Research shows that combining kidney and bone marrow transplants can help the body accept the new kidney without needing lifelong medication to suppress the immune system. In some studies, patients have successfully stopped taking these medications and maintained healthy kidney function, indicating the treatment's potential to create immune tolerance. ^{1 2 3 4 5}

Is the combined kidney and bone marrow transplant generally safe for humans?

Research shows that combined kidney and bone marrow transplants have been performed safely in humans, with some patients experiencing no rejection or serious complications, and maintaining good health and immune function over several years. ^{1 3 5 6 7}

How does the Kidney + Marrow Cell Transplant treatment differ from other treatments for kidney transplants?

This treatment is unique because it combines a kidney transplant with a bone marrow transplant to help the body accept the new kidney without needing lifelong immune-suppressing drugs. It aims to create a state called 'tolerance' where the immune system does not attack the transplanted organ, potentially reducing the side effects associated with traditional treatments. ^{1 2 3 6 8}

Research Team

Robert Lowsky, MD

Principal Investigator

Stanford University

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

Adults aged 18-65 with End Stage Renal Disease who haven't had a kidney transplant yet, match the donor in at least one HLA locus, and can sign informed consent. They must agree to use contraception for a year post-transplant and have no allergies to rabbit protein or history of certain diseases. Donors should be brain-dead individuals aged 16-55 without certain infections or malignancies.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.

My tissue sample will be kept cold for less than 24 hours before use.

I have severe kidney failure and am a candidate for my first kidney transplant.

Exclusion Criteria

I have smoked more than 5 pack-years, smoked within the last 10 years, or have a close relative with lung cancer.

I weigh more than 90kg or my BMI is over 35.

I have had cancer before, but not skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo a standard of care deceased donor kidney transplant followed by TLI/low dose TBI, ATG conditioning, and infusion of whole bone marrow cells from donor vertebral bodies.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including donor chimerism and antibody levels.

12 months

Long-term follow-up

Participants are monitored for persistence of donor chimerism and other long-term outcomes.

60 months

Treatment Details

Interventions

• Combined Deceased Donor Kidney and Hematopoietic Cell Transplants

Trial Overview The study is testing the safety and effectiveness of combining kidney transplants from deceased donors with vertebral body marrow cell infusions. It's a phase 1 trial where all participants receive the same treatment to see how well it works and what doses are safe.

Participant Groups

Group I: Phase I Study of Combined DD Kidney and HCT Transplant Experimental Treatment 1 Intervention

Single arm Phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

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]

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]

In a study involving seven patients with multiple myeloma and end-stage renal disease, combined kidney and bone marrow transplantation led to sustained renal function and tolerance without ongoing immunosuppression in three patients, demonstrating the potential for long-term success.

All patients achieved mixed chimerism, and five are alive with four showing no signs of myeloma up to 12.1 years post-transplant, indicating that this approach can effectively manage both renal and cancer conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. Spitzer, TR., Sykes, M., Tolkoff-Rubin, N., et al.[2022]

In a 10-year follow-up study of 11 kidney transplant recipients in China, the combination of donor hematopoietic stem cell (DHSC) infusion and total lymphoid irradiation (TLI) successfully induced immune tolerance, allowing for reduced immunosuppressive therapy while maintaining stable kidney function in most patients.

The protocol demonstrated safety, as none of the recipients developed myelosuppression or graft-versus-host disease (GVHD), and the risk of infection did not increase, highlighting the potential for this approach to improve long-term outcomes in kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerance induction with donor hematopoietic stem cell infusion in kidney transplantation: a single-center experience in China with a 10-year follow-up. Wang, X., Yang, C., Hu, L., et al.[2022]

References

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

Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance. [2022]

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

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

3. 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]

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

Further studies of veto activity in rhesus monkey bone marrow in relation to allograft tolerance and chimerism. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

Bone marrow transfusions in cadaver renal allografts: pilot trials with concurrent controls. [2019]

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

Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Tolerance induction with donor hematopoietic stem cell infusion in kidney transplantation: a single-center experience in China with a 10-year follow-up. [2022]

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

Preclinical and clinical studies for transplant tolerance via the mixed chimerism approach. [2019]