NCT07390539

B7-H3.CD28Z.CART in CNS Neoplasms

A Phase 1/1b Study of Autologous b7-h3 Chimeric Antigen Receptor t Cells (b7-h3.cd28z.Cart) in Children and Young Adults With Recurrent or Progressive Cns Neoplasms Expressing b7-h3 Target

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Robbie Majzner · Academic / Other
• Sex: All
• Age: 2 Years – 21 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this research study is to test the safety and effectiveness of a cell therapy at different doses for children and young adults with recurrent or progressive brain tumors. Recurrent/recurred means a tumor that has gone away and then came back. This cell therapy is called B7- H3.CD28Z.CART, referred to as B7-H3 CAR T cells. B7-H3 is a protein that is over-expressed on many tumor cells, making it a good target for cancer cell therapy. The names of the study investigational therapies involved in this study are: * Fludarabine (a type of chemotherapy) * Cyclophosphamide (a type of chemotherapy) * B7-H3 CAR T cells (a type of cellular therapy)

Detailed description

This is a single-institution, Phase 1/1b, open-label study to test the safety and effectiveness of a cell therapy at different doses for children and young adults with recurrent or progressive brain tumors. Recurrent/recurred means a tumor that has gone away and then came back. This cell therapy is called B7- H3.CD28Z.CART, referred to as B7-H3 CAR T cells. B7-H3 is a protein that is over-expressed on many tumor cells, making it a good target for cancer cell therapy. The U.S. Food and Drug Administration (FDA) has not approved B7-H3 CAR T cells as a treatment for any disease. Fludarabine and cyclophosphamide are standard lymphodepleting chemotherapy medications that are being used in this study to prepare the body for cell therapy. They are approved by the U.S. Food \& Drug Administration (FDA) for this purpose and are not intended to be treatment for recurrent or progressive brain tumors. The structure of the study will be by dose-escalation using a modified 3+3 design in two risk strata (standard risk, high risk), followed by a two-stage Phase 1b expansion at the recommended Phase 2 dose. Participation in this study is expected to last up to 15 years. It is expected that about 70 people will participate in this study.

Conditions

• Central Nervous System Neoplasms
• Brain Tumor
• Brain Tumor, Recurrent
• Brain Tumor, Pediatric
• Brain Tumor Adult
• Medulloblastoma
• Medulloblastoma, Childhood
• Medulloblastoma, Adult
• Medulloblastoma Recurrent
• Ependymoma
• Atypical Teratoid/Rhabdoid Tumor
• Embryonal Tumor With Multilayered Rosettes
• Pineoblastoma
• Leptomeningeal Disease

Interventions

Type	Name	Description
BIOLOGICAL	B7-H3.CD28Z.CART	Autologous CAR T cells targeting B7-H3 (CD276), administered intravenously (into the vein) per protocol.
DRUG	Fludarabine	Lymphodepleting chemotherapy administered intravenously per institutional standards.
DRUG	Cyclophosphamide	Lymphodepleting chemotherapy administered intravenously per institutional standards.

Timeline

• Start date: 2026-07-01
• Primary completion: 2030-08-31
• Completion: 2032-08-31
• First posted: 2026-02-05
• Last updated: 2026-02-05

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study