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

NCT06684639 | Recruiting Early Phase 1

• 1 other identifier: Yihai2024
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Relapsed; Refractory

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Duration of overall response (DOR)

  24 months

• Progression-free survival(PFS)

  24 months

• Overall survival(OS)

  24 months

Other Outcomes (2)

• The duration of CAR T-cells in vivo

  24 months

• CAR-T related cytokine expression

  24 months

Study Arms (1)

Experimental group

EXPERIMENTAL

GD2 positive relapsed or refractory neuroblastoma

Biological: GD2-CAR-T cell

Interventions

GD2-CAR-T cell BIOLOGICAL

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

Experimental group

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• The General Hospital of Western Theater Command: lead
• Yake Biotechnology Ltd.: collaborator

Study Sites (1)

The General Hospital of Western Theater Command

Chengdu, Sichuan, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hai Yi, Ph.D

  The General Hospital of Western Theater Command

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JunXia Wang, Ph.D

CONTACT

0086-28-86571605; lzwjxyy@163.com

Hai Yi, Ph.D

CONTACT

0086-28-86571279; yihaimail@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: November 12, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 20, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)