CAR-T Cell Therapy for Kidney Transplant Desensitization

Recruiting at 6 trial locations

Overseen By Mary Kaminski, PA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: BMI ≥30, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 31

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals who have waited over a year for a kidney transplant but face rejection from most donor kidneys. The trial combines CAR T cells (a type of immune therapy), specifically CART-BCMA, with chemotherapy to determine if it can safely reduce rejection risk. It seeks participants on dialysis with highly sensitive immune systems likely to reject nearly all donor kidneys. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that participants do not receive ongoing immunosuppression, including corticosteroids and other specific medications, from 90 days before joining the study. This suggests you may need to stop certain medications before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CAR T-cell therapies, such as CART-BCMA and huCART19, are being tested for safety and effectiveness in individuals awaiting kidney transplants. Studies have observed some side effects with CAR T-cells, including sudden kidney problems and imbalances in body salts, indicating potential risks with these treatments.

For huCART19, earlier research found it generally safe in a small group of patients. Most participants tolerated it well, although specific side effects weren't detailed in the provided information.

As this is an early-stage trial, the primary goal is to determine a safe dose and monitor for serious side effects. Safety information is still being collected, so researchers will closely monitor participants throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CART-BCMA and huCART19 for kidney transplant desensitization because these treatments use innovative CAR-T cell therapy. Unlike standard options, which often rely on immunosuppressive drugs to prevent organ rejection, CAR-T cell therapy works by engineering the patient's own immune cells to target and eliminate specific antibodies that cause rejection. This approach offers the potential for a more precise and durable response, reducing the need for chronic medication and its associated side effects. By directly modulating the immune system, these treatments could revolutionize how we manage transplant desensitization, potentially leading to better long-term outcomes for kidney transplant recipients.

What evidence suggests that CAR-T Cell Therapy might be an effective treatment for kidney transplant desensitization?

This trial will evaluate CAR-T cell therapies, specifically CART-BCMA and huCART19, to reduce the immune system's response in patients at high risk of rejecting donor kidneys while awaiting a transplant. Studies have shown that these therapies can target specific proteins in the immune system, potentially lowering the risk of rejection. Early findings suggest that using these CAR-T cells can prepare patients' bodies to accept more kidney matches. Although initial results are promising, further research is needed to confirm the effectiveness of these therapies for kidney transplant patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Vijay Bhoj, M.D., Ph.D.

Principal Investigator

University of Pennsylvania Medical Center: Transplantation

Ali Naji, MD, Ph.D.

Principal Investigator

University of Pennsylvania Medical Center: Transplantation

Alfred Garfall, MD

Principal Investigator

University of Pennsylvania Medical Center: Transplantation

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with kidney failure who have been on the transplant waitlist for over a year and are highly likely to reject a transplanted kidney. They must be able to consent, live near the study site, use contraception post-treatment, and meet specific health criteria like certain blood counts.

Inclusion Criteria

Subjects of reproductive potential must agree to use contraception for at least one year after CAR T Cell infusion

Your platelet count is equal to or greater than 150,000 per microliter.

I have been on the kidney transplant list for at least a year.

Exclusion Criteria

I have a condition like polycystic kidney disease or issues that increase my risk of urinary infections.

I haven't had B cell or antibody therapy in the last 6 months.

I am on continuous medication for blood thinning.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Subjects undergo leukapheresis to collect T cells for CAR T cell manufacturing

1 week

1 visit (in-person)

Lymphodepletion and CAR T Cell Infusion

Participants receive lymphodepleting chemotherapy followed by CART-BCMA and huCART-19 cell infusions

12 months

Up to 30 visits (in-person)

Post-Transplant Monitoring

If a transplant takes place, participants will have additional monitoring visits

9 visits

Long-term Follow-up

Long term follow up is required by the FDA for 15 years after receiving CAR T cell

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CART-BCMA
• Cyclophosphamide
• Fludarabine
• huCART19

Trial Overview The study tests if CAR T Cells (CART-BCMA + huCART19) combined with chemotherapy can safely lower immune rejection rates in patients awaiting kidney transplants. It involves multiple clinic visits over two years, plus long-term follow-up as required by the FDA.

How Is the Trial Designed?

Group I: Participant Cohorts Experimental Treatment 4 Interventions

* Safety Run-in phase (2 subjects at UPenn) * Cohort 1 (3-6 subjects) * Cohort 2 (3-6 subjects) * Cohort 3 (3-6 subjects)

CART-BCMA is already approved in United States for the following indications:

Approved in United States as CART-BCMA for:

• Experimental use for desensitization in kidney transplantation

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

University of Pennsylvania Clinical Cell and Vaccine Production Facility (CVPF)

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

The FDA is currently investigating potential links between BCMA- and CD19-directed CAR T-cell therapies and the development of secondary cancers in patients, highlighting a safety concern.

Despite these concerns, both the FDA and hematologists emphasize that the life-saving benefits of these immunotherapies for treating blood cancers outweigh the risks associated with secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Investigating CAR-Related T-cell Malignancies. [2023]

In a clinical trial involving 17 patients with relapsed and refractory multiple myeloma, the biepitope-targeting CAR T therapy (LCAR-B38M) showed a high overall response rate of 88.2%, with 13 patients achieving stringent complete response (sCR).

While the treatment was generally effective, 10 patients experienced mild cytokine release syndrome (CRS) and 6 had severe but manageable CRS, indicating that while adverse effects can occur, they are often clinically manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Xu, J., Chen, LJ., Yang, SS., et al.[2020]

In a study of 21 patients with relapsed and refractory multiple myeloma treated with BCMA-chimeric antigen receptor T cells (CART), 17 patients showed effective responses, including 10 achieving complete remission, indicating a promising efficacy of this treatment.

The treatment was associated with manageable adverse reactions, primarily cytokine release syndrome (CRS), which occurred in 20 patients but was mostly mild (Grade 1 or 2), demonstrating that BCMA-CART can be safely administered with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma]. Zhang, XY., Ding, HY., Gang, DX., et al.[2022]

Intravenous immunoglobulin (IVIG) is a key treatment for HLA desensitization in kidney transplantation, significantly improving transplantation rates according to a randomized, placebo-controlled trial.

Combining IVIG with rituximab has led to excellent outcomes in desensitization, while other agents like bortezomib and eculizumab show promise for patients with strong HLA antibodies, indicating a multi-faceted approach to overcoming transplantation barriers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modern approaches to incompatible kidney transplantation. Wongsaroj, P., Kahwaji, J., Vo, A., et al.[2020]

In a study involving seven patients receiving living-donor kidney transplants, pretransplant T-cell depletion with alemtuzumab did not lead to tolerance in human renal allografts, as all patients experienced reversible rejection episodes shortly after transplantation.

Despite the initial rejection episodes, patients were able to maintain graft function on reduced immunosuppression, primarily using sirolimus, indicating that while T-cell depletion is significant, it does not eliminate the risk of rejection and highlights the role of monocytes in the rejection process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Kirk, AD., Hale, DA., Mannon, RB., et al.[2022]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

CAR-T cell therapy utilizes genetically modified T cells that express an antibody fragment to specifically target and bind to cancer cells, enhancing the immune response against tumors.

This innovative approach represents a promising advancement in cancer treatment, as it harnesses the body's own immune system to identify and destroy cancer cells more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: From the Bench to the Bedside. Golubovskaya, V.[2020]

Costimulation blockade therapy, like belatacept, offers a targeted approach to managing the immune response in kidney transplant recipients, potentially reducing non-immune side effects associated with traditional immunosuppressive therapies.

While belatacept has shown promise in certain subgroups of kidney transplant patients, its use is limited due to an increased risk of acute rejection, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Costimulation Blockade in Kidney Transplant Recipients. van der Zwan, M., Hesselink, DA., van den Hoogen, MWF., et al.[2020]

In a phase 1 study involving 57 patients with relapsed/refractory multiple myeloma, LCAR-B38M CAR T cell therapy showed an impressive overall response rate of 88%, with 68% of patients achieving a complete response.

While the therapy had a manageable safety profile, with common adverse events including leukopenia and cytokine release syndrome, it demonstrated durable responses with a median progression-free survival of 15 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. Zhao, WH., Liu, J., Wang, BY., et al.[2020]

The fully human BCMA-specific CAR T-cell therapy, CT103A, demonstrated a remarkable overall response rate of 100% in 18 patients with relapsed/refractory multiple myeloma, with 72.2% achieving complete or stringent complete responses.

CT103A showed a favorable safety profile, with the most common adverse events being mild hematologic toxicities, and no cases of severe neurotoxicity were reported, indicating its potential as a promising treatment option for patients, including those who previously relapsed from murine BCMA CAR therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma. Wang, D., Wang, J., Hu, G., et al.[2022]

In a phase I study involving 25 patients with relapsed/refractory multiple myeloma, CART-BCMA therapy demonstrated clinical activity, with response rates of 44% in the lowest dose cohort and 64% in the highest dose cohort, indicating its potential effectiveness as a treatment.

While CART-BCMA infusions were associated with some serious side effects like cytokine release syndrome and neurotoxicity, these were mostly reversible, suggesting a manageable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. Cohen, AD., Garfall, AL., Stadtmauer, EA., et al.[2020]

Desensitization therapies for kidney transplant candidates, such as plasmapheresis and immunoadsorption, are often insufficient alone to achieve lasting reductions in harmful anti-HLA antibodies, leading to high rates of antibody-mediated rejection (AMR).

Combining low-dose intravenous immunoglobulins (IVIg) with plasmapheresis has shown improved survival rates compared to dialysis, but still results in unacceptable AMR rates, highlighting the need for new strategies like bortezomib, a proteasome inhibitor, as a potential alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desensitization in kidney transplantation: review and future perspectives. Abu Jawdeh, BG., Cuffy, MC., Alloway, RR., et al.[2015]

In a study evaluating alternatives to anti-CD154 mAb for inducing renal allograft tolerance, belatacept was found to be effective, with three out of five recipients achieving long-term kidney survival without ongoing immunosuppression.

In contrast, the use of abatacept did not result in comparable chimerism or graft survival, highlighting belatacept's potential as a clinically applicable option for promoting tolerance in kidney transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates. Yamada, Y., Ochiai, T., Boskovic, S., et al.[2023]

In a study of 99 patients with relapsed/refractory multiple myeloma undergoing BCMA CAR-T cell therapy, acute kidney injury (AKI) occurred in 25.3% of cases, typically within 15 days post-infusion, indicating a significant risk associated with this treatment.

Key independent risk factors for developing AKI included elevated serum creatinine levels after chemotherapy preconditioning and the severity of cytokine release syndrome (CRS), with higher grades of CRS leading to a notably increased incidence of AKI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors of acute kidney injury during BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma. Lyu, Y., Zhang, M., Wei, G., et al.[2022]

Citations

1. cancer.gov cancer.gov/clinicaltrials/NCI-2025-03203

CAR-T Cell Therapy for Desensitization in Kidney ... This research study is for people who have been waiting for a kidney transplant for at least one year, and who have a cPRA of 99.5% or higher.

2. withpower.com withpower.com/trial/phase-1-renal-insufficiency-2024-d429a

CAR-T Cell Therapy for Kidney Transplant Desensitization This research study is for people who have been waiting for a kidney transplant for at least one year, and who have a cPRA of 99.5% or higher.

3. ajkd.org ajkd.org/article/S0272-6386(25)00876-5/fulltext

Role of Chimeric Antigen Receptor–Expressing Cell ... Existing management strategies for immune-mediated kidney diseases have not achieved satisfactory clinical outcomes. Preliminary studies suggest ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10287817/

CAR-T Cells and the Kidney: Insights from the WHO Safety ... Our study, based on the WHO drug safety database, provides an overview of the array of renal complications associated with CAR-T cell therapy. A ...

5. academic.oup.com academic.oup.com/ckj/article/18/8/sfaf219/8195527

Desensitization in HLA-incompatible kidney transplant recipients A positive CDC T-cell XM, when an autoantibody has been excluded, has traditionally been accepted as a contraindication to kidney ...