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

NCT ID: NCT06684639

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-01

Study Completion Date

2030-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Neuroblastoma

Keywords

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Neuroblastoma Relapsed Refractory

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental group

GD2 positive relapsed or refractory neuroblastoma

Group Type EXPERIMENTAL

GD2-CAR-T cell

Intervention Type BIOLOGICAL

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

Interventions

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GD2-CAR-T cell

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. All cases were diagnosed as neuroblastoma with positive expression of GD2 antigen in tumor cells. Informed consent of patient or guardian.
2. Diagnosis of recurrent/refractory neuroblastoma.
3. At least 2 weeks or 5 half-lives (whichever is shorter) from the beginning of preconditioning chemotherapy after prior systemic treatment.
4. Toxic reactions caused by previous antitumor therapy must be stabilized and restored to ≤ grade 1.
5. Over 1 years old, under 18 years old.
6. Physical strength score 0-3 (ECOG standard).
7. No obvious active infection.
8. Expected survival ≥3 months
9. 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%.
10. 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).

Exclusion Criteria

1. 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.
2. There is an uncontrollable infection, including fungal, bacterial, viral or other.
3. Known human immunodeficiency virus (HIV) infection.
4. 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.
5. Existing or past CNS disease, such as seizures, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any CNS-related autoimmune disease.
6. 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).
7. 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.
8. Any medical condition that may affect the evaluation of safety or efficacy.
9. Have had severe rapid hypersensitivity reactions to any of the drugs to be used in this study.
10. Live vaccine should be administered within ≤6 weeks before starting the pretreatment regimen.
11. Pregnant or lactating female subjects.
12. 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.
13. 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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Yake Biotechnology Ltd.

INDUSTRY

Sponsor Role collaborator

The General Hospital of Western Theater Command

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hai Yi, Ph.D

Role: PRINCIPAL_INVESTIGATOR

The General Hospital of Western Theater Command

Locations

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The General Hospital of Western Theater Command

Chengdu, Sichuan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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JunXia Wang, Ph.D

Role: CONTACT

Phone: 0086-28-86571605

Email: [email protected]

Hai Yi, Ph.D

Role: CONTACT

Phone: 0086-28-86571279

Email: [email protected]

Facility Contacts

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hai Yi

Role: primary

Other Identifiers

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Yihai2024

Identifier Type: -

Identifier Source: org_study_id