Using CAR-T cell therapy to treat Multi-Drug Resistant Nephrotic Syndrome

Study of Therapeutic Efficacy of Anti-CD19 Chimeric Antigen Receptor T Lymphocytes (CAR-T) Cells in Patients With Multi-drug Resistant SRNS

This study is testing a new CAR-T cell therapy to see if it can help children and adults with a tough kidney condition that doesn't respond to regular treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine (other)
• Drugs / interventions: rituximab, CAR-T, CAR T, cyclophosphamide
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06842589 on ClinicalTrials.gov

What this trial studies

This trial investigates the safety and efficacy of anti-CD19 CAR-T cell therapy for patients suffering from Multi-Drug Resistant Steroid Resistant Nephrotic Syndrome (MDR-SRNS). Given the lack of effective treatments for this condition, which can lead to kidney failure, the study aims to explore a novel approach using genetically modified T cells to target and eliminate disease-related cells. Participants will include children and adults aged 2 and older who have not responded to standard treatments. The study is designed to provide critical data on the potential of CAR-T therapy in treating this challenging autoimmune disease.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 2 years and older diagnosed with MDR-SRNS who have not responded to standard steroid treatments.

Not a fit: Patients with other autoimmune diseases requiring long-term systemic treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a new treatment option for patients with MDR-SRNS, potentially improving their quality of life and reducing the risk of kidney failure.

How similar studies have performed: While CAR-T therapy has shown success in treating other autoimmune diseases, its application in nephrotic syndrome is novel and untested.

Eligibility criteria

Inclusion Criteria:

* 1\. Age ≥2 years old, gender unlimited;
* 2.Diagnosed with SRNS according to the 2021 Kidney Disease: Improving Global Outcomes （KDIGO） Guidelines and have not achieved a complete response after 12 months of treatment with two standard doses of hormone replacement drugs with different mechanisms of action or relapse of disease activity after remission (at least one of the two drugs is a calcineurin inhibitor such as cyclosporine or tacrolimus; Other hormone replacement drugs include Mycophenolate Mofetil, cyclophosphamide, Taitacept or rituximab); Or if no remission has been achieved after 3 to 6 months of adequate treatment with one calcineurin inhibitor, if the researcher judges that the benefits outweigh the risks and the patient or guardian has fully informed consent, the patient can be considered for inclusion.Patients with other diseases, such as systemic lupus erythematosus, requiring long-term systemic treatment with glucocorticoids or immunosuppressants, may be considered for inclusion after the investigator determines that the benefits outweigh the risks and the patient or guardian has fully informed consent;
* 3\. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
* 4\. The functions of important organs are basically normal: Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2# Liver function: Asparagus cochinchinensis transaseminase (AST) and Alanine Aminotransferase (ALT)≤3.0 upper limit of normal, Total Bilirubin (TBIL) in serum ≤2.0×upper limit of normal; Lung function: No serious lung lesions, SpO2≥92%;
* 5\. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
* 6\. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
* 7\. Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.

Exclusion Criteria:

* 1\. Received CAR T cell therapy or other gene-modified cell therapy previously;
* 2\. Patients had a cerebrovascular accident or seizure, or other active central nervous system disease within 6 months;
* 3\. Genetic tests have confirmed hereditary kidney disease;
* 4\. Renal biopsy has been confirmed as immunoglobulin A nephropathy, idiopathic membranous nephropathy or membranoproliferative glomerulonephritis;
* 5\. Renal replacement therapy has been or is being performed within 3 months prior to transfusion. (if acute kidney injury factors were considered, patients with chronic kidney disease were excluded, and the benefits outweighed the risks as determined by the investigator and with the full and informed consent of the patient or guardian could be considered for inclusion);
* 6\. Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
* 7\. Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs;
* 8\. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;
* 9\. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
* 10\. Macrophage activation syndrome occurred within 1 month prior to screening;
* 11\. Received live vaccine within 4 weeks before screening;
* 12\. Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
* 13\. Tested positive in Blood pregnancy test;
* 14\. Patients who participated in other clinical study within 1 months prior to enrollment;
* 15\. Any other conditions that the investigators deem it unsuitable for the study.

Where this trial is running

Hangzhou, Zhejiang

• Children's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Jianhua Mao, PhD

Conditions: Multi-Drug Resistant Nephrotic Syndrome, CAR-T Cell Therapy, car-t