This is an investigator-initiated trial to evaluate the efficacy and safety of BCMA/CD70-targeted CAR-T in the treatment of refractory pediatric rheumatic diseases.
Age ≥5 years old.
To meet the diagnostic criteria of refractory B-cell-related pediatric rheumatic diseases, including but not limited to juvenile dermatomyositis, polyarticular juvenile idiopathic arthritis, systemic sclerosis, and primary Sjogren's syndrome.
The classification criteria of RJDM must meet (1) and any one of (2)-(5): (1) Patients who are intolerant or unresponsive to glucocorticoids and at least 2 immunosuppressants, and the duration of adequate hormone therapy should be at least 6 months; (2) The disease progresses rapidly and/or involves organs such as lungs, heart and gastrointestinal tract; (3) Calcification of subcutaneous or muscle and joint tissues; (4) Repeated rashes or skin ulcers; (5) Repeated or persistent myasthenia(muscle MRI indicates extensive, diffuse edema or the Childhood Myositis Assessment Scale(CMAS) should be less than 48 points, and at least two of the following five core measurement indicators should have abnormal results: Physician Global Assessment(PhGA) ≥2cm, Patient Global Assessment(PtGA) ≥2cm, Disease Activity Score(DAS) ≥2 points, Childhood Health Assessment Questionnaire(C-HAQ) ≥0.25 points, muscle enzyme level > 1.5×upper limit of normal);
RJDM with anti-synthetase syndrome who are positive for anti-synthetase antibody and those with immune-mediated necrotizing myopathy who are positive for SRP or HMGCR antibody can be included.
Severe major organ involvement related to the primary disease, such as severe pulmonary hypertension (PHA) (mean arterial pressure > 45mmHg).
primary immunodeficiency or severe secondary immunodeficiency that has not been corrected.
accompanied by serious or active or uncontrollable infectious diseases, including but not limited to active tuberculosis, latent tuberculosis infection, active viral hepatitis,etc.
Evidence of active malignant disease or diagnosis of malignant tumor(including hematological malignancies and solid tumors, except resected and cured skin basal cell carcinoma).
Single group
BCMA/CD70-targetd CAR-T
Biological/VaccineSubjects underwent lymphocytetion cheotherapy and then received a single intravenous cell infusion
To evaluate the safety of CAR-T in the treatment of refractory pediatric rheumatic diseases [Safety and Tolerability]
The incidence of adverse events after CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) including the type, frequency and severity of adverse events.
The Total Improvement Score (TIS) of CAR-T in the treatment of refractory juvenile dermatomyositis [Effectiveness]
The proportion of subjects who achieved the minimal, moderate, and major clinical response of the Total Improvement Score (TIS) within 6 months after reinfusion.
Minimal disease activity, inactive disease and remission of CAR-T in the treatment of refractory polyarticular juvenile idiopathic arthritis [Effectiveness]
The proportion of subjects who achieved minimal disease activity, inactive disease and remission within 6 months.
Ped ACR 30/50/70/90/100 of CAR-T in the treatment of refractory polyarticular juvenile idiopathic arthritis [Effectiveness]
The proportion of subjects who achieved Ped ACR 30/50/70/90/100 within 6 months.
Cmax of BCMA/CD70 CAR-T cells [PK parameter]
The Peak Plasma concentration (Cmax) of amplified BCMA/CD70 CAR-T cells in peripheral blood after reinfusion.
Tmax of BCMA/CD70 CAR-T cells [PK parameter]
The time of amplified BCMA/CD70 CAR-T cells in peripheral blood to reach the maximum concentration (Tmax).
AUC28d/90d of BCMA/CD70 CAR-T cells [PK parameter]
The area under the plasma concentration versus time curve at 28 days /90 days after reinfusion (AUC28d/90d).
The clearance degree of B cells [PD parameter]
The clearance degree of B cells at each time point.
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