4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma

NCT04637503 | Recruiting Phase 1

• 1 other identifier: GIMI-IRB-20010
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple 4SCAR-T cell therapy which targets GD2, PSMA and CD276 surface antigens in patients with relapsed and refractory neuroblastoma (NB). Another goal of the study is to understand the function of the multi-CAR-T cells and their persistency in the patients.

Conditions

Neuroblastoma

Keywords

CART; chimeric antigen receptor; adoptive T cell transfer; GD2, PSMA, CD276, B7-H3

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  Determine the toxicity profile the GD2, PSMA and CD276 4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0

  3 year

Secondary Outcomes (5)

• Anti-tumor effects

  3 year

• The expansion of CAR-T cells

  3 year

• The anti-tumor activity after CAR-T infusions

  1 year

• The cytokine secretion profile after CAR-T infusions

  1 year

• Survival time of the patients

  3 year

Study Arms (1)

effectiveness of CAR-T cells targeting GD2, PSMA and CD276

EXPERIMENTAL

Gene-modified T cells are designed to kill tumor cells through specific recognition of GD2, PSMA and CD276. This study will evaluate the side effects and effective doses of GD2, PSMA and CD276 CAR-T cells in treating refractory and recurrent NB

Biological: GD2, PSMA and CD276 CAR-T cells

Interventions

GD2, PSMA and CD276 CAR-T cells BIOLOGICAL

infusion, for 1x10\^6\~1x10\^7 cells/kg via IV

effectiveness of CAR-T cells targeting GD2, PSMA and CD276

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with tumors have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive or recurrent.
• The expression status of GD2, PSMA and CD276 antigens of the tumor will be determined for eligibility. Positive expression is defined by GD2, PMSA and CD276 antibody staining results based on immunohistochemistry or flow cytometry analyses.
• Body weight greater than or equal to 10 kg.
• Age: ≥1 year and ≤ 65 years of age at the time of enrollment.
• Life expectancy: at least 8 weeks.
• Prior Therapy:
• There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.
• Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
• At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen.
• At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
• At least 1 week since any radiation therapy at the time of study entry.
• Karnofsky/jansky score of 60% or greater.
• Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
• Pulse Ox greater than or equal to 90% on room air.
• Liver function: defined as alanine transaminase (ALT) \<3x upper limit of normal (ULN), aspartate aminotransferase (AST) \<3x ULN; serum bilirubin and alkaline phosphatase \<2x ULN.

You may not qualify if:

• Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
• Untreated central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
• Previous treatment with other genetically engineered GD2, PSMA and CD276 CART cells.
• Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
• Patients who require systemic corticosteroid or other immunosuppressive therapy.
• Evidence of tumor potentially causing airway obstruction.
• Inability to comply with protocol requirements.
• Insufficient CART cells availability.

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead

Study Sites (1)

Shenzhen Geno-Immune Medical Institute

Shenzhen, Guangzhou, 518000, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Gaucher Disease

Interventions

ganglioside, GD2

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; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Central Study Contacts

Lung-Ji Chang, PhD

CONTACT

+86 0755-86573763; c@szgimi.org

Study Design

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

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: November 19, 2020
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)