NCT07222735

Hypofractionated Radiation in Combination With B7-H3-CAR T Cells for Pediatric Patients With Relapsed/Refractory Sarcomas

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

RAD3CAR is a phase I study designed to evaluatethe safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy. Primary objective: \- To evaluate the safety of B7-H3-CAR T cell therapy after priming with hypofractionated radiation therapy (HFRT) and lymphodepleting chemotherapy in patients ≤ 21 years of age with relapsed/refractory B7-H3+ sarcomas. Secondary objectives: * To describe the antitumor activity of B7-H3-CAR T cells in combination with HFRT * To determine if B7-H3-CAR T cells traffic to tumor sites after combination treatment with HFRT

Detailed description

This study is a phase I study designed to describe the safety of B7-H3-CAR T cells and lymphodepletion in combination with hypofractionated radiation therapy for the treatment of pediatric patients with B7-H3+ sarcoma. The study will contain two-part eligibility criterion: one to proceed with autologous apheresis and manufacturing of CAR T cells, and a second to proceed with CAR T cell treatment. The primary intervention is the administration of autologous B7-H3-CAR T cells, after priming with HFRT and administration of lymphodepleting chemotherapy. Peripheral blood mononuclear cells (PBMC) will be collected by autologous apheresis. Treatment will include HFRT to at least one site of disease, administered in parallel with a single course of lymphodepleting chemotherapy (fludarabine/cyclophosphamide) and followed by CAR T cell infusion. Participants are evaluated for a post-treatment tumor biopsy and may choose to be evaluated for a pre-treatment tumor biopsy. Participants who meet specified criteria will be eligible for optional additional treatment courses.

Conditions

• Sarcoma
• Childhood Osteosarcoma
• Childhood Rhabdomyosarcoma
• Childhood Soft Tissue Sarcoma
• Ewing Sarcoma

Interventions

Type	Name	Description
DRUG	Fludarabine	Intravenously on day -5, -4, -3 and -2
DRUG	Cyclophosphamide	Intravenously on day -3, -2
DRUG	B7-H3-CAR T Cells	Intravenously on day 0
RADIATION	Radiation Therapy	5 or 8 treatment sessions (fractions), scheduled to complete on Day -2

Timeline

• Start date: 2026-01-21
• Primary completion: 2030-11-05
• Completion: 2031-11-05
• First posted: 2025-10-30
• Last updated: 2026-02-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study