A Study on the Efficacy of GD2-CAR T Cells in the Treatment of Neuroblastoma

Официальное название

An Open Clinical Study on the Safety and Efficacy of Autologous GD2-CAR T Cells in the Treatment of Relapsed Refractory Neuroblastoma

Обзор

Neuroblastoma (NB) is a malignant tumor of the sympathetic nervous system.Chemotherapy and autologous hematopoietic stem cell transplantation are the main treatments for neuroblastoma, and the prognosis of patients with high-risk recurrence and refractory treatment is very poor. There is a large unmet medical need in patients with relapsed refractory neuroblastoma, and further research into new therapeutic approaches is needed for these patients.GD2 is a dissialic ganglioside expressed by neuroectodermal tumors. The proportion of GD2 expression in neuroblastoma is up to 100%, so GD2 is a specific target for neuroblastoma immunotherapy and an ideal target for CAR-T treatment of neuroblastoma.

Подробное описание

The subjects received the target dose of GD2-CAR-T from 1×106 to 1×108 /kg. Each subject will start with a low dose of 1×106/kg and if there are no significant side effects will be increased to the next dose until the maximum tolerated dose is reached. A variety of adverse events (including neurological events, hematological events, infections, and secondary tumors) will be collected from the time of infusion of CAR T cells to 24 months after infusion. To understand the complete response rate (CR) and partial response rate (PR) at 3 months; Recurrence rate, progression-free survival (PFS) and overall survival (OS) after 1 to 5 years of GD2-CAR-T reinfusion; The amount and duration of GD2-CAR-T in vivo.

Вмешательства

• Биопрепарат GD2-CAR-T cell
  Split intravenous infusion of GD2-CAR-T cells \[dose escalating infusion of (1-100)x10\^6 GD2-CAR-T cells/kg\]

Первичные конечные точки

• Number of Adverse Events [Срок оценки: 24 months]
• Overall response rate (ORR) [Срок оценки: 24 months]

Вторичные конечные точки (3)

• Duration of overall response (DOR) [Срок оценки: 24 months]
• Progression-free survival(PFS) [Срок оценки: 24 months]
• Overall survival(OS) [Срок оценки: 24 months]

Критерии участия

Критерии включения

• All cases were diagnosed as neuroblastoma with positive expression of GD2 antigen in tumor cells. Informed consent of patient or guardian.
• Diagnosis of recurrent/refractory neuroblastoma.
• At least 2 weeks or 5 half-lives (whichever is shorter) from the beginning of preconditioning chemotherapy after prior systemic treatment.
• Toxic reactions caused by previous antitumor therapy must be stabilized and restored to ≤ grade 1.
• Over 1 years old, under 18 years old.
• Physical strength score 0-3 (ECOG standard).
• No obvious active infection.
• Expected survival ≥3 months
• Adequate kidney, liver, lung and heart function, defined as creatinine clearance (estimated by the Cockcroft Gault formula) > 60 mL/min; Serum ALT/AST ≤ 2.5 ULN; Total bilirubin ≤1.5 ULN, excluding subjects with Gilbert's syndrome; Cardiac ejection fraction ≥ 50%, echocardiography confirmed centropericardial effusion, and ECG showed no clinically significant abnormal findings. There was no clinically significant pleural effusion. Baseline blood oxygen saturation under indoor ventilation was > 92%.
• The serum pregnancy test results of fertile women must be negative (women who have undergone surgical sterilization or at least 2 years after menopause are considered to be infertile).

Критерии исключения

• The subject has had other malignancies, non-melanoma skin tumors, carcinoma in situ (e.g. Cervix, bladder, breast), unless disease-free survival of at least 3 years.
• There is an uncontrollable infection, including fungal, bacterial, viral or other.
• Known human immunodeficiency virus (HIV) infection.
• Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with latent or prehepatitis B infection (defined as HBcAb positive and HBsAg negative) can be enrolled only if PCR tests for HBV DNA are negative. In addition, these subjects were required to undergo a monthly PCR test for HBV DNA. Participants who are serologically positive for HCV antibodies can also be enrolled if their PCR test results for HCV RNA are negative.
• Existing or past CNS disease, such as seizures, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any CNS-related autoimmune disease.
• Serious heart disease, such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months prior to screening, or any grade 3 (moderate) or 4 (severe) heart disease (according to the New York Heart Society Functional Grading Method NYHA).
• A history of myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart disease in the 12 months prior to enrollment.
• Any medical condition that may affect the evaluation of safety or efficacy.
• Have had severe rapid hypersensitivity reactions to any of the drugs to be used in this study.
• Live vaccine should be administered within ≤6 weeks before starting the pretreatment regimen.
• Pregnant or lactating female subjects.
• Male or female subjects who do not consent to effective contraception from the time they sign informed consent until 6 months after completing immune cell therapy.
• Subjects judged by the investigator had difficulty in completing all visits or procedures required by the study protocol (including follow-up visits), or were not compliant enough to participate in the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The General Hospital of Western Theater Command — Чэнду

Идентификаторы

NCT: NCT06684639 · Yihai2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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