CAR T-Cell Therapy for Kidney Failure

Overseen By Melhem Solh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northside Hospital, Inc.

Must not be taking: Systemic corticosteroids

Disqualifiers: CNS disorders, Uncontrolled infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, descriptive study designed to assess the feasibility of administering CAR T therapy among patients with moderate to severe renal impairment using dose adjusted lymphodepleting chemotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use high-dose corticosteroids (more than 20mg/day prednisone or equivalent) within 72 hours of receiving CAR-T therapy.

What data supports the idea that CAR T-Cell Therapy for Kidney Failure is an effective treatment?

The available research does not provide specific data on CAR T-Cell Therapy for Kidney Failure. Instead, it focuses on kidney transplantation as a treatment for kidney failure. The research shows that kidney transplantation has high success rates, with patient and graft survival rates ranging from 92% to 95%. This suggests that kidney transplantation is currently considered the most effective treatment for end-stage kidney disease, offering significant benefits over long-term dialysis. There is no direct comparison or data available for CAR T-Cell Therapy in the context of kidney failure in the provided research. ^{1 2 3 4 5}

Is CAR T-cell therapy generally safe for humans, especially concerning kidney health?

CAR T-cell therapy has been linked to kidney issues, such as acute kidney injury (AKI), in some patients. About 18-30% of patients may experience AKI, but most cases are reversible with proper treatment. While serious side effects like cytokine release syndrome can occur, studies have shown that CAR T-cell therapy can be safely administered even to patients with existing kidney problems. ^{6 7 8 9 10}

How is CAR T-cell therapy different from other treatments for kidney failure?

CAR T-cell therapy is unique because it involves modifying a patient's own immune cells to target specific cells, which is different from traditional treatments for kidney failure that typically focus on managing symptoms or replacing kidney function through dialysis or transplant. This therapy is more commonly used in cancer treatment and is not a standard treatment for kidney failure, making it a novel approach in this context. ^{6 7 11 12 13}

Eligibility Criteria

This trial is for people with certain blood cancers (like multiple myeloma, leukemia, or lymphoma) who also have moderate to severe kidney problems. They must be strong enough for chemotherapy and not have central nervous system disorders, uncontrolled infections, or be taking high doses of steroids.

Inclusion Criteria

My bone marrow is healthy enough for strong chemotherapy.

I am able to get out of my bed or chair and move around.

My kidney function is reduced, with a filtration rate of 60 mL/min or less.

Exclusion Criteria

I have a disorder affecting my brain or nervous system.

I do not have any infections or conditions that could affect the study.

I haven't taken high doses of steroids within 3 days before CAR-T therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive dose-adjusted lymphodepleting chemotherapy with fludarabine and cyclophosphamide based on renal function

1 week

CAR T Cell Therapy Infusion

Participants receive CAR T cell therapy infusion

1 day

Follow-up

Participants are monitored for safety and effectiveness after CAR T cell therapy infusion

90 days

Treatment Details

Interventions

• CAR T-cell Therapy
• Cyclophosphamide
• Fludarabine

Trial Overview The study is testing if CAR T-cell therapy can work in patients with poor kidney function by adjusting the dose of chemo drugs Cyclophosphamide and Fludarabine used before the therapy.

Participant Groups

Group I: Severe Renal Dysfunction Experimental Treatment 2 Interventions

Several renal dysfunction will receive a 40% dose reduction of fludarabine and no dose reduction for cyclophosphamide.

Group II: Moderate Renal Dysfunction Experimental Treatment 2 Interventions

Moderate renal dysfunction will receive a 20% dose reduction of fludarabine and no dose reduction for cyclophosphamide.

Group III: Dialysis Participants Experimental Treatment 2 Interventions

Participants on dialysis will receive a 50% dose reduction of fludarabine and a 25% dose reduction of cyclophosphamide.

CAR T-cell Therapy is already approved in United States, European Union for the following indications:

Approved in United States as CAR T-cell Therapy for:

• Relapsed or refractory B-cell acute lymphoblastic leukemia
• Relapsed or refractory B-cell non-Hodgkin's lymphoma
• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory follicular lymphoma
• Relapsed or refractory multiple myeloma

Approved in European Union as CAR T-cell Therapy for:

• Relapsed or refractory B-cell acute lymphoblastic leukemia
• Relapsed or refractory B-cell non-Hodgkin's lymphoma
• Relapsed or refractory mantle cell lymphoma

Who Is Running the Clinical Trial?

Northside Hospital, Inc.

Lead Sponsor

Trials

26

Recruited

1,100+

Blood and Marrow Transplant Group of Georgia

Collaborator

Trials

9

Recruited

320+

Findings from Research

In a study of 100 consecutive kidney transplant patients, the overall patient survival rate was an impressive 98%, and the graft survival rate was 96%, indicating significant improvements in transplantation outcomes.

The analysis included both living and cadaveric donors, with the majority of donor deaths due to cerebrovascular disease, highlighting the importance of donor health in transplantation success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes of 100 Consecutive Kidney Transplantations in a 3-Year Period: A Single-Center Experience. Alfaro Sanchez, CI., Molina Higueras, MJ., Moiron Fernandez-Felechosa, JP., et al.[2018]

In a study of 28 HIV-infected patients who underwent kidney transplantation, the procedure was found to be safe, with an 82.1% survival rate and all patients achieving undetectable HIV RNA levels at the last follow-up.

The study noted a high incidence of acute rejection (19 rejections in 16 patients), but the use of integrase inhibitors in antiretroviral therapy helped reduce potential drug interactions with immunosuppressive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy). Izzo, I., Casari, S., Bossini, N., et al.[2018]

In a study of 4445 patients on the waitlist for kidney transplants, those who received a transplant had significantly longer survival times compared to those who continued on dialysis, with benefits observed across all ages.

The estimated survival time increase was notable, with an average of 3.01 years for 60-year-olds and 2.48 years for 70-year-olds, indicating that kidney transplants are beneficial regardless of waiting time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure. Strohmaier, S., Wallisch, C., Kammer, M., et al.[2022]

Kidney transplantation is considered the most effective treatment option for patients suffering from end-stage kidney disease, offering significant improvements in health and quality of life.

The procedure has shown promising outcomes, making it a preferred choice over other treatment modalities for managing severe kidney failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Aspects of Renal Immunology: Current Status and Future Perspectives. Eleftheriadis, T., Crespo, M.[2022]

Kidney transplantation is the most effective treatment for end-stage renal failure, providing significant benefits over hemodialysis by freeing patients from its constraints and addressing socio-economic issues related to chronic treatment.

The study reports on the initial 30 months of kidney transplantation at Hôpital Charles Nicolle in Tunis, detailing the early steps, therapeutic regimens, and complications encountered during this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The first thirty months of kidney transplantation in Tunisia]. Kechrid, C., el Ouakdi, M., Ben Abdallah, T., et al.[2006]

CAR-T cell therapy is a revolutionary cancer treatment but is associated with a risk of acute kidney injury (AKI), highlighting the need for nephrologists to be aware of this potential side effect.

Understanding the causes of AKI in patients receiving CAR-T cell therapy is crucial for effective clinical management, and the review offers guidance for better diagnosis and treatment of this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy and nephrotoxicity: From diagnosis to treatment strategies. Zhou, H., Yang, M., Cui, L., et al.[2021]

In a study of 32 patients undergoing CAR-T therapy, pre-existing chronic kidney disease (CKD) did not significantly affect progression-free survival (PFS) or overall survival (OS), with median PFS of 8.8 months for CKD patients compared to 2.9 months for those without CKD.

Acute kidney injury (AKI) post-CAR-T also showed no significant impact on PFS or OS, indicating that neither CKD nor AKI adversely affected the outcomes of CAR-T therapy in this cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients. Ahmed, G., Bhasin-Chhabra, B., Szabo, A., et al.[2022]

CAR T-cell therapy can lead to acute kidney injury (AKI) in about 30% of patients, with 18% of those studied experiencing AKI after treatment, but most cases are reversible with proper care.

Despite concerns, CAR T-cell therapy has been successfully administered to dialysis-dependent patients with refractory diffuse large B-cell lymphoma, indicating that it can be safe even in those with significant renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review. Khan, I., Khan, N., Wolfson, N., et al.[2023]

A review of 152 pre-clinical studies on CAR T-cell therapy revealed that only 7.9% were specifically designed to assess or improve safety, indicating a significant gap in safety evaluation prior to clinical use.

Key safety parameters, such as the use of immunocompetent animal models and comprehensive monitoring of physiological responses, were inadequately reported, suggesting that current pre-clinical data may not reliably predict the safety of CAR T-cell therapies in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety. Maharshi, V., Diksha, D., Gupta, P.[2022]

CAR-T cell therapy is effective for treating acute lymphoblastic leukemia and diffuse large B-cell lymphoma, but it can lead to significant toxicities, including cytokine release syndrome in up to 40% of patients.

Acute kidney injury occurs in nearly 20% of patients after CAR-T infusion, with contributing factors such as severe cytokine release syndrome and prior stem cell transplants, highlighting the need for careful monitoring and management of kidney health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute kidney injury after CAR-T cell infusion. Rousseau, A., Zafrani, L.[2022]

Anti-CD19 CAR T-cell therapy is effective for treating relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma, but it can lead to complications such as acute kidney injury, often linked to cytokine release syndrome.

In a case study of a kidney transplant recipient, kidney function declined after CAR T-cell therapy, with biopsy indicating mild tubulointerstitial nephritis, suggesting that kidney injury may occur through indirect mechanisms rather than direct infiltration by CAR T cells or lymphoma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Kidney Injury Following Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma in a Kidney Transplant Recipient. Melilli, E., Mussetti, A., Linares, GS., et al.[2023]

In a study of 166 patients with relapsed/refractory diffuse large B cell lymphoma receiving CAR T cell therapy, those with renal impairment (10.2% of the cohort) did not experience significantly worse renal or survival outcomes compared to those without renal impairment.

However, patients who developed acute kidney injury (AKI) post-treatment had poorer clinical outcomes, indicating that while CAR T cell therapy is feasible for patients with renal impairment, monitoring for AKI is crucial as it is associated with higher inflammatory cytokine levels and worse progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis. Wood, AC., Perez, AP., Arciola, B., et al.[2023]

In a study of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T cell therapy, the incidence of acute kidney injury (AKI) was found to be 30%, with most cases being mild (grade 1) and no patients requiring dialysis.

Despite the occurrence of AKI, most patients recovered their kidney function within 30 days, indicating that with proper monitoring and management, the risks associated with CAR-T therapy can be effectively mitigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Kidney Injury after CAR-T Cell Therapy: Low Incidence and Rapid Recovery. Gutgarts, V., Jain, T., Zheng, J., et al.[2022]

References

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

Short-Term Outcomes of 100 Consecutive Kidney Transplantations in a 3-Year Period: A Single-Center Experience. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy). [2018]

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

Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure. [2022]

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

Molecular Aspects of Renal Immunology: Current Status and Future Perspectives. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[The first thirty months of kidney transplantation in Tunisia]. [2006]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy and nephrotoxicity: From diagnosis to treatment strategies. [2021]

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

Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients. [2022]

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

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review. [2023]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Acute kidney injury after CAR-T cell infusion. [2022]

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

Acute Kidney Injury Following Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma in a Kidney Transplant Recipient. [2023]

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

Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis. [2023]

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

Acute Kidney Injury after CAR-T Cell Therapy: Low Incidence and Rapid Recovery. [2022]