NCT05298995

GD2-CAR T Cells for Pediatric Brain Tumours

Phase I Study of Anti-GD2 Chimeric Antigen Receptor-Expressing T Cells in Pediatric and Young Adult Patients Affected by Relapsed/Refractory Central Nervous System Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: Bambino Gesù Hospital and Research Institute · Academic / Other
• Sex: All
• Age: 6 Months – 30 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the safety and efficacy of iC9-GD2-CAR T-cells, a third generation (4.1BB-CD28) CAR T cell treatment targeting GD2 in paediatric or young adult patients affected by relapsed/refractory malignant central nervous system (CNS) tumors. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.

Detailed description

The study will consist of a Phase I, dose escalation phase aimed at evaluating the safety and feasibility of intravenous injections of autologous iC9-GD2-CAR T-cells in patients with refractory/relapsed malignant CNS tumors. Considering the peculiar potential risks associated with the treatment of CNS tumors, the study has been designed to enrol patients in 3 different arms depending on the histology and location of the disease. This model of enrollment is aimed at testing the safety sequentially, starting from categories of patients at lower risk of severe intracranial hypertension first, and subsequently proceeding with patients at proportionally increased risk. In particular, the three arms explored will be relapsed or refractory: * ARM A: MB/other embryonal tumor * ARM B: Hemispheric HGG * ARM C: Thalamic HGG, DMG, DIPG and other rare CNS tumors not included in Arm A and B Eligible patients will undergo leukapheresis in order to harvest T cells, which will be manufactured to obtain the autologous CAR T product iC9-GD2-CAR T-cells, a GD2-targeting CAR T product. Briefly, the patients will be treated with a lymphodepleting regimen containing conventional chemotherapic agents and subsequently will receive a single infusion of GD2-CART01. Moreover, the product contains a suicide gene safety switch (namely inducible Caspase 9): in case of relevant toxicities, the patient will receive the dimerizing agent in order to activate the apoptotic pathway in the infused T cells. After infusion of CAR T cells, the patients will enter a 5-year active follow-up period (for disease follow-up). A conventional 15-year follow-up will be performed as per regulatory requirements in patients receiving gene therapy.

Conditions

• Brain Tumor, Pediatric
• Medulloblastoma, Childhood
• Embryonal Tumor
• High Grade Glioma
• Diffuse Midline Glioma
• Diffuse Intrinsic Pontine Glioma
• Brain Tumor Adult

Interventions

Type	Name	Description
BIOLOGICAL	GD2-CART01 (iC9-GD2-CAR T-cells)	Following a lymphodepleting treatment with conventional chemotherapy, patients will be treated with 1.0 to 6.0 x 10⁶/kg GD2 Chimeric Antigen Receptor (CAR) positive T cells, infused i.v. as a single dose

Timeline

• Start date: 2023-11-09
• Primary completion: 2027-11-01
• Completion: 2038-11-01
• First posted: 2022-03-28
• Last updated: 2025-02-05

Locations

1 site across 1 country: Italy