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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2+
SponsorThe Children's Hospital of Zhejiang University School of Medicine

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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%;

Disqualifiers

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;

Trial design

Design model

Single group

Treatments tested in this trial

  • anti-BCMA/CD70 CAR-T cells

    Biological/Vaccine

    Three dose groups (0.3×105/kg, 1×105/kg, 3×105/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.

Treatment groups

18 Participants
are divided into 1 treatment group
Group A: CAR-T treatment groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

The safety of CAR-T cell therapy in patients with MDR SRNS

Incidence and severity of Adverse Events (AEs) and Serious Adverse Event(SAEs),including changes in laboratory values,Electrocardiograph(ECG) and vital signs assessed by CommonTerminology Criteria for Adverse Events (CTCAE) v5.0.

Time frame
3 months

Secondary outcomes

1

The efficiency of CAR-T cell therapy in patients with MDR SRNS

Complete response and partial response rate (complete response defined as Urinary protein/creatinine ratio (uPCR) ≤200 mg/g for 3 consecutive days, partial response is defined as a 50% or more reduction in proteinuria from baseline and 200mg/g \< uPCR \<2000mg/g)

Time frame
6 months
2

Cellular kinetics

The Peak Plasma concentration (Cmax) of amplified BCMA/CD70 CAR-T cells in peripheral blood after reinfusion, the time to reach the maximum concentration (Tmax) and area under the plasma concentration versus time curve at 28 days /90 days after reinfusion (AUC28d/90d).

Time frame
3 months

Other outcomes

Sponsors and contacts

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