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

Not Applicable

Recruiting

• Conditions: Sarcoma; Childhood Osteosarcoma; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Ewing Sarcoma
• Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: B7-H3-CAR T Cells; Radiation: Radiation Therapy

• Registration Number: NCT07222735
• Lead Sponsor: St. Jude Children's Research Hospital

Brief 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.

Study Timeline

• Study First Submitted: 2025-10-28
• Study First Submitted QC: 2025-10-28
• Study First Posted: 2025-10-30
• Status Verified: 2025-11
• Last Update Submitted: 2025-11-18
• Last Update Posted: 2025-11-19
• Study Start: 2025-12-05
• Primary Completion: 2030-11-05
• Study Completion: 2031-11-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAD3CAR Treatment	Fludarabine	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.
RAD3CAR Treatment	Cyclophosphamide	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.
RAD3CAR Treatment	B7-H3-CAR T Cells	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.
RAD3CAR Treatment	Radiation Therapy	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.

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT) rate	up to 4 weeks after CAR T cell infusion	Proportion of evaluable participants experiencing DLTs
Incidence of adverse events (AEs)	up to 4 weeks after CAR T cell infusion	AEs will be assessed and graded using CTCAE v5.0, except for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which will be graded according to ASTCT consensus guidelines. AEs will be summarized and reported descriptively

Secondary Outcome Measures

Name	Time	Method
Clinical antitumor activity	4-12 weeks after CAR T cell infusion	Best overall response after treatment as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and if applicable bone marrow evaluation
B7-H3-CAR T cell trafficking to tumor sites	2 weeks after CAR T cell infusion	Evaluate for the presence of B7-H3-CAR T cells in post-treatment tumor biopsies

Trial Locations

Locations (2)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States