Title: Safety and efficacy of CAR-T cell therapy for relapsed/refractory neuroblastoma and desmoplastic small round cell tumors: a single-arm, open-label trial.
The CART used in this study will be provided by Shanghai YaKe Biotechnology Ltd.
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;
Patients with increased intracranial pressure or altered consciousness;
Patients who have received radiation therapy within 2 weeks prior to infusion;
Patients with active hepatitis B (defined as HBV DNA > 500 IU/mL) or hepatitis C (HCV RNA positive);
HIV-positive patients or patients with a positive syphilis test;
Single group
CART therapy
Biological/VaccineGD2/B7H3 CAR T-cell therapy
To evaluate the safety of CAR-T cells in relapsed/refractory neuroblastoma and desmoplastic small round cell tumor patients.
1. To evaluate the safety of the infusion of CAR T cells at different escalating/deescalating doses and establish the dose limiting toxicity (DLT) of the cellular product. Toxicity will be evaluated according to the CTC AE scale, version 4.0. DLT will be defined as any of the following that is not pre-existing, due to infection or to underlying malignancy and that may be considered possibly, probably or definitely related to the study cellular products. (1) Non-hematologic DLT is any grade 3 or 4 non-hematologic toxicity; (2) Hematologic DLT is defined as any grade 4 hematologic toxicity related to infusion ; (3) Grade 4 reactions related to infusion; (4) Death related to CAR T cells infusions. The incidence of grade 3-5 toxicities, with a main attention to severe Cytokine Release Syndrome (CRS), will be evaluated. 2. To determine the optimal dose of CAR transduced T cells resulting in the control of the disease without inducing unacceptable levels of toxicity (MTD) .
To evaluate the efficacy of CAR-T cells in relapsed/refractory neuroblastoma and desmoplastic small round cell tumor patients.
To assess the antitumor effect of iC9-GD2-CAR T cells at 6 weeks, 3 and 6 months post-infusion. The Best Overall Response Rate (BOR) and the proportion of neuroblastoma patients achieving complete remission (CR) will be assessed according to INRC. The Best Overall Response Rate (BOR) and the proportion of desmoplastic small round cell tumor patients achieving complete remission (CR) will be assessed according to RECIST 1.1.
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Sun Yat-Sen University Cancer Center
Lead sponsor
Sun Yat-sen University
Sponsor institution
Yake Biotechnology Ltd.
Collaborator
Dongguan Taixin Hospital
Collaborator
