RecruitingPhase 1NCT06553898

Study of Therapeutic Efficacy of CAR-T Cell Therapy in Patients With MDR-SRNS

Study of Therapeutic Efficacy of Anti-B Cell Maturation Antigen（BCMA）/Cluster of Differentiation 70(CD70 )CAR-T Cells in Patients With Multi-drug Resistant SRNS

Sponsor

The Children's Hospital of Zhejiang University School of Medicine

Enrollment

18 participants

Start Date

Aug 13, 2024

Study Type

INTERVENTIONAL

Conditions

CAR-T Cell Therapy Multi-Drug Resistant Nephrotic Syndrome

Summary

This is an investigator-initiated trial aimed at assessing the safety and efficacy of anti-BCMA/CD70 CAR-T cells in the treatment of patients with Multi-drug resistant SRNS

Eligibility

Min Age: 2 Years

Inclusion Criteria7

\. Age ≥2 years old, gender unlimited;
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;
\. Renal biopsy was performed and the pathological type was determined to be minimal lesion nephropathy(MCD) or focal segmental glomerulosclerosis (FSGS);
\. 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%;
\. Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
\. Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
\. 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 Criteria15

\. Received CAR T cell therapy or other gene-modified cell therapy previously;
\. Patients had a cerebrovascular accident or seizure, or other active central nervous system disease within 6 months;
\. Genetic tests have confirmed hereditary kidney disease;
\. Renal biopsy has been confirmed as immunoglobulin A nephropathy, idiopathic membranous nephropathy or membranoproliferative glomerulonephritis;
\. 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);
\. Renal replacement therapy has been or is being performed within 3 months prior to transfusion;
\. 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;
\. 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;
\. 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;
\. Macrophage activation syndrome occurred within 1 month prior to screening;
\. Received live vaccine within 4 weeks before screening;
\. Patients with malignant diseases such as tumors before screening, or with other serious life-threatening diseases;
\. Tested positive in Blood pregnancy test;
\. Patients who participated in other clinical study within 1 months prior to enrollment;
\. Any other conditions that the investigators deem it unsuitable for the study.