16 Participants Needed

Immunological Tolerance Therapy for Kidney Transplant Rejection

RW
DL
Overseen ByDana Levin-Lopez, MPH
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: University of California, Los Angeles
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if Belumosudil can help kidney transplant patients accept their new kidney without long-term immune-suppressing drugs. It targets patients with partially matched or slightly mismatched donors. The drug works by boosting special immune cells that help the body accept the new kidney.

Do I need to stop my current medications to join the trial?

The trial requires that you have not taken immunosuppressive medications within one year of the study treatment, except for short-term corticosteroids that were stopped at least 4 weeks before the kidney transplant. Other specific medication restrictions are not mentioned, so it's best to discuss your current medications with the study team.

Is the treatment generally safe for humans?

The research does not provide specific safety data for the treatment under the names Belumosudil, Rezurock, Rholistiq, KD025, SLx-2119, Donor CD34+, or CD3+. However, it mentions that some immunosuppressive therapies in kidney transplantation have been associated with toxicities, and safety issues have led to the discontinuation of certain treatments in the past.12345

What makes the treatment Belumosudil, Donor CD34+, CD3+ unique for kidney transplant rejection?

This treatment is unique because it combines Belumosudil, which is known for its use in other conditions like chronic graft-versus-host disease, with donor cell therapy (CD34+ and CD3+ cells) to potentially induce immune tolerance, reducing the need for long-term immunosuppressive drugs that can have significant side effects.678910

Are You a Good Fit for This Trial?

Adults over 18 eligible for kidney and stem cell transplants can join this trial if they have a matched living donor, are not pregnant, agree to use contraception, live near UCLA Medical Center, and have good heart, liver, and lung function. Excluded are those with certain infections or diseases requiring immunosuppression, recent drug abuse history, very high BMI or previous organ transplants.

Inclusion Criteria

Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker
INR and/or PTT < 1.5X upper limits of institutional normal
I agree to use effective birth control methods if I'm of reproductive age.
See 34 more

Exclusion Criteria

I have been treated with rATG or am allergic to rabbit proteins.
Pregnant or lactating
INR and/or PTT ≥ 1.5X upper limits of institutional normal
See 21 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Subjects undergo a conditioning regimen of rATG and TLI followed by kidney transplantation and infusion of donor CD34 and CD3 cells.

Immediate post-transplant
In-patient stay for transplantation and initial treatment

Treatment

Participants receive a triple immunosuppressive regimen and belumosudil. Corticosteroids taper from day 0 to month 4, tacrolimus taper from day 1 to month 18, and mycophenolate from day 11 to month 12. Belumosudil is administered from day 28 to month 24.

24 months
Regular follow-up visits for monitoring and biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment, including chimerism measurement, graft function monitoring, and protocol biopsies.

36 months

What Are the Treatments Tested in This Trial?

Interventions

  • Belumosudil
  • Donor CD34+, CD3+
Trial Overview The study is testing the safety and effectiveness of belumosudil in improving transplant tolerance when given alongside a combined kidney and hematopoietic stem cell transplant from either a half-matched related donor or an unrelated donor with minimal HLA mismatches.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Immune tolerance in mismatched kidney transplant recipientExperimental Treatment1 Intervention
Our goal is to establish this regimen as a novel, safe and effective approach for induction of transplant tolerance in HLA single haplotype-matched related and HLA mismatched unrelated recipients of combined Hematopoietic Stem Cell Transplant(HSCT)/ Kidney Transplant (KT). Patients will undergo conditioning with rATG and TLI, followed by infusion of hematopoeitic stem cells from the same donor, a triple immunosuppressive regimen, and receive belumosudil following the kidney transplant. Immunosuppression taper will be stopped and/or immunosuppression will be resumed for any of the following conditions: (1) loss of chimerism 2) clinical or pathological evidence of acute rejection and (3) clinical or pathological evidence of graft vs host disease.

Belumosudil is already approved in United States, Canada for the following indications:

🇺🇸
Approved in United States as Rezurock for:
  • Chronic graft-versus-host disease (cGVHD) in patients aged 12 years and older after failure of at least two prior lines of systemic therapy
🇨🇦
Approved in Canada as Rholistiq for:
  • Chronic graft-versus-host disease (cGVHD) in adult and pediatric patients 12 years or older

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials
1,594
Recruited
10,430,000+

Published Research Related to This Trial

A modified release tacrolimus formulation (MR4) is currently in phase III trials and aims to improve kidney transplant outcomes by allowing once-daily administration while maintaining the same therapeutic target levels as the original formulation.
Belatacept (LEA29Y), a second-generation immunosuppressant, has shown comparable efficacy to ciclosporin in phase II trials and is now in phase III trials, indicating its potential as a viable alternative for kidney transplant patients.
Immunotherapy for De Novo renal transplantation: what's in the pipeline?Tedesco Silva, H., Pinheiro Machado, P., Rosso Felipe, C., et al.[2018]
In a study of 316 kidney transplant recipients over 2 years, belatacept-based immunosuppression showed a significantly lower incidence of reduced kidney function (eGFR <45 ml/min) compared to tacrolimus, indicating better long-term kidney health.
However, belatacept was associated with a higher rate of biopsy-proven acute rejection compared to tacrolimus, suggesting a trade-off between reduced nephrotoxicity and increased rejection risk.
Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial.Kaufman, DB., Woodle, ES., Shields, AR., et al.[2023]
Desensitization using carfilzomib and lulizumab in a non-human primate model significantly reduced donor-specific antibodies and improved kidney graft survival, with a median survival time of 64.8 days compared to 5.8 days in control animals.
The treatment shifted the immune system towards a more naive phenotype, maintaining regulatory T cells and increasing naive CD4 T and B cells, although all desensitized subjects eventually developed antibody-mediated rejection (AMR) and graft failure.
Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model.Schroder, PM., Schmitz, R., Fitch, ZW., et al.[2022]

Citations

Immunotherapy for De Novo renal transplantation: what's in the pipeline? [2018]
Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial. [2023]
New developments in immunosuppressive therapy in renal transplantation. [2019]
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]
Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model. [2022]
Achieving incompatible transplantation through desensitization: current perspectives and future directions. [2015]
Summary of the Third International Workshop on Clinical Tolerance. [2023]
Mechanisms of induction of renal allograft tolerance in CD45RB-treated mice. [2021]
Association of rapamycin and co-stimulation blockade using anti-B7 antibodies in renal allotransplantation in baboons. [2017]
Low dose busulfan facilitates chimerism and tolerance in a murine model. [2015]
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