CAR T-Cell Therapy for Kidney Failure
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Northside Hospital, Inc.
Must not be taking: Systemic corticosteroids
Disqualifiers: CNS disorders, Uncontrolled infection, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.12345
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.678910
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.67111213
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.
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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.
Trial 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 (CAR T-cell Therapy)
- Cyclophosphamide (Alkylating agents)
- Fludarabine (Anti-metabolites)
Trial OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: Severe Renal DysfunctionExperimental Treatment2 Interventions
Several renal dysfunction will receive a 40% dose reduction of fludarabine and no dose reduction for cyclophosphamide.
Group II: Moderate Renal DysfunctionExperimental Treatment2 Interventions
Moderate renal dysfunction will receive a 20% dose reduction of fludarabine and no dose reduction for cyclophosphamide.
Group III: Dialysis ParticipantsExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Caitlin GuzowskiAtlanta, GA
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Who Is Running the Clinical Trial?
Northside Hospital, Inc.Lead Sponsor
Blood and Marrow Transplant Group of GeorgiaCollaborator
References
Short-Term Outcomes of 100 Consecutive Kidney Transplantations in a 3-Year Period: A Single-Center Experience. [2018]The results of kidney transplantation have improved significantly in the last decade with patient and graft survival rates that range from 92% to 95%.
Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy). [2018]Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre.
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]Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias.
Molecular Aspects of Renal Immunology: Current Status and Future Perspectives. [2022]Kidney transplantation is the most promising treatment available for patients with end-stage kidney disease [...].
[The first thirty months of kidney transplantation in Tunisia]. [2006]Kidney transplantation is actually the best replacement therapy for the end stage renal failure. It sets free the hemodialysed patient from the hemodialysis restraint and contributes to solve the socio-economic problems risen by chronic hemodialysis. The authors report the results of this technic during the first 30 months of kidney transplantation in the "Hôpital Charles Nicolle" of Tunis. They describe the first steps which led to kidney transplantation, the therapeutic regimens, the medico-legal problems and the specific complications observed during this start period.
Chimeric antigen receptor T cell therapy and nephrotoxicity: From diagnosis to treatment strategies. [2021]Chimeric antigen receptor T (CAR-T) cell therapy is a breakthrough in cancer treatment. With the widespread use of this therapy, increasing evidence is available that CAR-T cell therapy is associated with acute kidney injury (AKI). Nephrologists need to understand the potential nephrotoxicity arising from CAR-T cell therapy. Determining the cause of AKI is a key factor of clinical management. This review focuses on the clinical use of CAR-T cell therapy and the cause and outcomes of nephrotoxicity with its use. We also provide clinical suggestions for clinicians towards both better diagnosis and management of AKI in those receiving CAR-T cell therapy.
Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients. [2022]Chimeric antigen receptor T-cell (CAR-T) therapy is standard-of-care in relapse/refractory aggressive B-cell non-Hodgkin lymphoma. There are limited data regarding the impact of pre-existing chronic kidney disease (CKD) and acute kidney injury (AKI) post CAR-T and we sought to evaluate these in our patients.
Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review. [2023]Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies. However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys. In this review, we summarized the available evidence on the safety profile of CAR T-cell therapy in patients with pre-existing renal insufficiency/AKI and in those who develop AKI as a result of CAR T-cell therapy. With a 30% incidence of AKI post-CAR T-cell, various pathophysiological mechanisms, such as CRS, hemophagocytic lymphohistiocytosis (HLH), TLS, serum cytokines, and inflammatory biomarkers, have been shown to play a role. However, CRS is commonly reported as an underlying mechanism. Overall, 18% of patients in our included studies developed AKI after receiving CAR T-cell therapy, and most cases were reversible with appropriate therapy. While phase-1 clinical trials exclude patients with significant renal toxicity, two studies (Mamlouk et al. and Hunter et al.) reported successful treatment of dialysis-dependent patients with refractory diffuse large B-cell lymphoma, and demonstrated that CAR T-cell therapy and lymphodepletion (Flu/Cy) can be safely administered.
Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety. [2022]Serious adverse reactions have been reported with the use of Chimeric Antigen Receptor (CAR) T-cell therapy in a clinical setting despite the success of these products in pre- clinical stages of development.
Acute kidney injury after CAR-T cell infusion. [2022]Chimeric antigen receptor T (CAR-T)-cell, an adaptive immune therapy is approved for patients with acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Its use and subsequent toxicities are expected to rise in the coming years. The main toxicities are cytokine release syndrome, hemophagocytic lymphohistiocytosis and immune effector cell associated neurotoxicity syndrome. Cytokine release syndrome is observed in up to 40% of patients. Almost 20% of patient suffer from acute kidney injury after CAR-T cell infusion. Associated factors are high-grade cytokine release syndrome, a prior autologous or allogeneic stem cell transplantation andrequirement of intensive care unit. Several mechanisms may contribute to the occurrence of acute kidney injury after CAR-T infusion: hypoperfusion during cytokine release syndrome, cytokine injury, T cell infiltration, tumor lysis syndrome and sepsis-induced injury. Kidney injury is associated with substantial increase in morbi-mortality.
Acute Kidney Injury Following Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma in a Kidney Transplant Recipient. [2023]Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a newer and effective therapeutic option approved for patients with relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Acute kidney injury is a complication of CAR T-cell therapy that can result in kidney failure. In most cases, it is thought to be related to hemodynamic changes due to cytokine release syndrome. Kidney biopsy in this clinical scenario is usually not performed. We report on a kidney transplant recipient in his 40s who developed a posttransplant lymphoproliferative disorder of B-cell origin refractory to conventional treatments and received anti-CD19 CAR T-cell therapy as compassionate treatment. Beginning on day 12 after CAR T-cell infusion, in the absence of clinical symptoms, a progressive decline in estimated glomerular filtration rate of the kidney graft occurred. A subsequent allograft biopsy showed mild tubulointerstitial lymphocyte infiltrates, falling into a Banff borderline-changes category and resembling an acute immunoallergic tubulointerstitial nephritis. Neither CAR T cells nor lymphomatous B cells were detected within the graft cellular infiltrates, suggesting an indirect mechanism of kidney injury. Although kidney graft function partially recovered after steroid therapy, the posttransplant lymphoproliferative disorder progressed and the patient died 7 months later.
Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis. [2023]Patients with renal impairment (RI) are typically excluded from trials evaluating chimeric antigen receptor (CAR) T cell therapies. We evaluated the outcomes of patients with RI receiving standard of care (SOC) CAR T cell therapy for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this retrospective, single-center cohort study of patients with R/R DLBCL treated with SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) after 2 or more prior lines of therapy, renal and survival outcomes were compared based on RI and fludarabine dose reduction (DR) status. RI was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 as determined by the Modification of Diet in Renal Disease equation using day -5 creatinine (Cr) values. Acute kidney injury (AKI) was identified and graded using standard Kidney Disease: Improving Global Outcomes criteria. Renal recovery was considered to occur if Cr was within .2 mg/mL of baseline by day +30. Fludarabine was considered DR if given at <90% of the recommended Food and Drug Administration label dose. Among 166 patients treated with CAR T cell therapy were 17 patients (10.2%) with baseline RI and 149 (89.8%) without RI. After CAR T cell infusion, the incidence of any grade AKI was not significantly different between patients with baseline RI and those without RI (42% versus 21%; P = .08). Similarly, severe grade 2/3 AKI was seen in 1 of 17 patients (5.8%) with baseline RI and in 11 of 149 patients (7.3%) without RI (P = 1). Decreased renal perfusion (28 of 39; 72%) was the most common cause of AKI, with cytokine release syndrome (CRS) contributing to 17 of 39 AKIs (44%). Progression-free survival (PFS) and overall survival (OS) did not differ between patients with RI and those without RI or between those who received standard-dose fludarabine and those who received reduced-dose fludarabine. In contrast, patients with AKI had worse clinical outcomes than those without AKI (multivariable PFS: hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2 to 3.7; OS: HR, 3.9; 95% CI, 2.1 to 7.4). Notably, peak inflammatory cytokine levels were higher in patients who experienced AKI. Finally, we describe 2 patients with end-stage renal disease (ESRD) on dialysis who received lymphodepletion and CAR T cell therapy. Baseline renal function did not affect renal or efficacy outcomes after CAR T cell therapy in DLBCL. On the other hand, patients with AKI went on to experience worse clinical outcomes. AKI was commonly related to CRS and high peak inflammatory cytokine levels. CAR T cell therapy is feasible in patients with ESRD and requires careful planning of lymphodepletion.
Acute Kidney Injury after CAR-T Cell Therapy: Low Incidence and Rapid Recovery. [2022]Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5- to