Safety and Efficacy of CAR-T Cell Therapy for Relapsed/refractory Neuroblastoma and Desmoplastic Small Round Cell Tumors: a Single-arm, Open-label Trial.
Aims: 1. To evaluate the safety and efficacy of GD2/B7H3 CAR-T therapy for relapsed/refractory neuroblastoma, and observe its pharmacokinetic/pharmacodynamic characteristics and the survival of CAR-T cells in relapsed/refractory neuroblastoma patients. 2. To evaluate the safety and efficacy of GD2/B7H3 CAR-T therapy for relapsed/refractory desmoplastic small round cell tumor, and observe its pharmacokinetic/pharmacodynamic characteristics and the survival of CAR-T cells in desmoplastic small round cell tumor patients. Patients: Relapsed/refractory neuroblastoma; Relapsed/refractory desmoplastic small round cell tumor. CAR-T therapy: Lymphodepletion treatment will be performed within 14 days prior to CAR-T cell infusion: intravenous chemotherapy based on fludarabine 25mg/m² and cyclophosphamide 500mg/m² for 1 to 3 days. CAR-T cells will then be infused intravenously, with a dosage of 1.00 to 10.00 × 10⁶/kg of CAR-positive T cells. Research period: CAR-T cell infusion will be followed up for one year, or until adverse events resolve, progression occurs, or the patient transitions to other treatments. Outcome measures: Incidence of adverse events related to CAR-T therapy, as well as their intensity and duration; Pharmacokinetic/pharmacodynamic characteristics of CAR-T in patients and the survival of CAR-T cells. Overall response rate (ORR) after CAR-T cell infusion, including complete response (CR) and partial response (PR); Overall survival (OS), progression-free survival (PFS), event-free survival (EFS), time to progression (TTP), and duration of response (DOR) after CAR-T cell infusion;
• Patients who are diagnosed as relapsed/refractory neuroblastoma or relapsed/refractory desmoplastic small round cell tumors;
• Age 1-50 years, any gender;
• Agree to participate in the trial and sign a written informed consent form;
• Expected survival of ≥12 weeks;
• Karnofsky performance status (for patients ≥16 years) or Lansky performance status (for patients \<16 years) (Appendix 1) must be at least 50;
• Good function of major organs:
‣ Liver function: ALT ≤ 5 times the upper limit of normal for the corresponding age, and bilirubin ≤ 2.0 mg/dL, except for patients with Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome who have bilirubin ≤ 3.0 times the upper limit of normal and direct bilirubin ≤ 1.5 times the upper limit of normal may be included;
⁃ Renal function: Plasma creatinine ≤ 1.5 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m²;
⁃ Pulmonary function: Oxygen saturation ≥ 95% in room air;
⁃ Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 45%;
• Patients using the following medications must meet the following conditions:
• Steroids: Steroid treatment doses must be stopped at least 2 weeks before CAR-T infusion. However, physiological replacement doses of steroids are allowed; Immunosuppressants: Any immunosuppressive drugs must be stopped at least 4 weeks before enrollment; Anti-proliferative treatments other than lymphodepleting chemotherapy within two weeks before infusion; CNS disease prophylaxis must be stopped 1 week prior to CAR-T infusion (e.g., intrathecal methotrexate injection);
• Patients of childbearing potential (both male and female) must agree to use reliable contraception methods (hormonal or barrier methods or abstinence) with their partner until at least 12 months after CAR-T cell infusion, and until two consecutive flow cytometry or PCR tests show no CAR-T cells in the body;
• If the subject cannot provide suitable T cells for CAR-T preparation, T cells from a healthy donor may be collected for preparation.