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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: GD2-CAR-T cell

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Hai Yi, Ph.D; Phone Number: 0086-28-86571279; Email: yihaimail@163.com
• Study Contact Backup: Name: JunXia Wang, Ph.D; Phone Number: 0086-28-86571605; Email: lzwjxyy@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • The General Hospital of Western Theater Command
      • Contact: hai Yi; Phone Number: 0086-28-86571279; Email: yihaimail@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; GD2 positive relapsed or refractory neuroblastoma	Biological: 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]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Adverse events are evaluated with CTCAE V4.03	24 months
Overall response rate (ORR)	ORR includes CR, PR,MR.SD,PD.Complete response (CR)#All components CR.Partial response (PR)#PR in at least one component and all other components CR,minimal disease (bone marrow), PR or not involved at baseline.Minor response (MR)#PR or CR in at least one component but at least one other component with SD; no component with PD.Stable disease (SD)#SD in one component with no better than SD or not involved at baseline in any other component, no component with PD.Progressive disease (PD)#Any component with PD.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	PFS will be assessed from the CAR-T cell infusion to progression, death or last follow-up.	24 months
Duration of overall response (DOR)	Duration of overall response will be assessed from the CAR-T cell infusion to progression, death or last follow-up.	24 months
Overall survival(OS)	OS will be assessed from the CAR-T cell infusion to death or last follow-up.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The duration of CAR T-cells in vivo	The time of CAR-T cells' persistence in blood and the copies of CAR-T cells	24 months
CAR-T related cytokine expression	CAR-T related cytokine expression.	24 months

Collaborators and Investigators

• Sponsor: The General Hospital of Western Theater Command
• Collaborators: Yake Biotechnology Ltd.
• Investigators: Principal Investigator: Hai Yi, Ph.D, The General Hospital of Western Theater Command

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: November 9, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; Neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma
• Other Study ID Numbers: Yihai2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No