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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to kidney transplants for individuals with End Stage Renal Disease (ESRD) who qualify for a transplant. Researchers combine a kidney transplant with a special infusion of marrow cells (blood-forming cells) from the same deceased donor to determine if it helps the body better accept the new kidney. This combined procedure is called Combined Deceased Donor Kidney and Hematopoietic Cell Transplants. The primary goal is to assess the method's safety and effectiveness. Ideal participants have ESRD, are on the waitlist for a deceased donor kidney, and have a matching HLA type with the donor. As a Phase 1 trial, this research aims to understand how this innovative treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking approach.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combined kidney and bone marrow transplants have been safely performed in humans. Some patients did not experience rejection or serious side effects. Studies indicate that non-myeloablative HSCT, a type of bone marrow transplant, was safe and helped the body accept the new kidney more easily.

Other research using drugs like TLI/TBI/ATG, which prepare the body for transplant, showed promise in calming the immune system, making it more accepting of the new organ. Additionally, combining kidney transplants with bone marrow from a donor has been considered safe and feasible with medications like cyclophosphamide and fludarabine.

Overall, these findings suggest that this type of transplant can be well-tolerated. However, as this is a phase 1 study, the main focus is on assessing safety and how well participants can handle the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard kidney transplant procedures, which often involve just the organ transplant, this treatment combines a deceased donor kidney transplant with a hematopoietic cell transplant. This dual approach aims to help the body accept the new kidney more easily by fostering immune tolerance, potentially reducing the need for long-term immunosuppressive drugs. Researchers are excited about this treatment because it introduces marrow cells from the donor, which may "teach" the recipient's immune system to recognize the new kidney as part of the body, thus minimizing rejection risks and enhancing long-term transplant success.

What evidence suggests that this treatment might be an effective treatment for immune tolerance?

Research has shown that combining kidney and bone marrow transplants can be done safely in people. In this trial, participants will receive a combined deceased donor kidney and hematopoietic cell transplant. Patients in previous studies who received these transplants did not experience serious rejection. One study showed that the transplanted organs functioned well for over 11 years in all patients following a similar treatment plan. Another study found that recipients' bodies accepted the new organ with minimal medication. These findings suggest that this combined transplant method could lead to better long-term results for patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Robert Lowsky, MD

Principal Investigator

Stanford University

Stephan Busque, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8185903/

Combined kidney and hematopoeitic cell transplantation to ... The patients enrolled in the tolerance induction protocol had 100% actuarial graft survival over an observation period of over 11 years from 2005 to 2016. The ...

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. withpower.com withpower.com/trial/phase-1-10-2021-b402b

Kidney + Marrow Cell Transplant for Immune Tolerance Research shows that combined kidney and bone marrow transplants have been performed safely in humans, with some patients experiencing no rejection or serious ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.995243/full

Immune tolerance induced by hematopoietic stem cell ... In the United States, the average 1-year and 5-year graft survival of deceased-donor kidney transplant recipients is 94.3% and 76.3%, ...

5. journals.lww.com journals.lww.com/kidney360/fulltext/2024/07000/short_term,_mid_term,_and_long_term_outcomes_after.14.aspx

Short-Term, Mid-Term, and Long-Term Outcomes after ... Transplantation of kidneys with AKI is associated with satisfactory short-term and long-term outcomes and should be pursued to increase the donor pool.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4867066/

Combined Bone Marrow and Kidney Transplantation for the ... The focus of this review will be the induction of specific tolerance through hematopoietic chimerism following combined bone marrow and kidney transplantation.

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. onclive.com onclive.com/view/non-myeloablative-hsct-regimen-shows-potential-for-immune-tolerance-in-haploidentical-living-donor-combined-kidney-hematopoietic-transplant

Non-Myeloablative HSCT Regimen Shows Potential for ... Non-myeloablative HSCT with TLI/TBI/ATG conditioning was safe and active in eliciting immune quiescence and tolerance.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6624971/

Haploidentical hematopoietic cell and kidney ... Combined haploidentical HCT/kidney transplantation is safe and feasible with posttransplantation cyclophosphamide. Fludarabine can be used for conditioning ...