NCT05835687

Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).

Detailed description

Treatment on this study includes four (4) B7-H3-CAR T cell infusions over a 4 week period. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells using a 3+3 study design and a 4 week evaluation period. Follow up will occur on this protocol for 1 year after the final B7-H3-CAR T cell infusion and then continue on an institutional long-term follow up protocol to complete 15 years post-infusion.

Conditions

• Central Nervous System Neoplasms
• Atypical Teratoid/Rhabdoid Tumor
• Diffuse Midline Glioma, H3 K27M-Mutant
• Ependymoma
• High Grade Glioma
• Glioblastoma
• Medulloblastoma

Interventions

Type	Name	Description
DRUG	B7-H3-CAR T cells	Autologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells). Four (4) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.

Timeline

• Start date: 2023-04-27
• Primary completion: 2028-03-01
• Completion: 2028-03-01
• First posted: 2023-04-28
• Last updated: 2026-01-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study