This study focuses on aggressive brain tumors in children and young adults, including diffuse midline glioma (DMG), high-grade glioma (HGG), and other rare central nervous system (CNS) tumors such as medulloblastoma, embryonal tumors, AT/RT, ependymoma, and glioneuronal tumors. Many of these tumors express a protein called GD2, which helps researchers target them.
The therapy uses a patient’s own immune cells (T cells), which are genetically modified to recognize and attack GD2-positive tumor cells. These modified cells are called CAR T cells. In this study, the CAR T cells are enhanced with a gene called C7R, which helps them survive longer in the body and potentially fight tumors more effectively.
Standard treatments for these tumors are limited. Previous studies showed that GD2-targeted CAR T cells could recognize brain tumors but didn’t last long in the body. This trial builds on that research by adding the C7R gene and testing a new delivery approach to improve persistence and antitumor activity.
The study includes two main parts:
Procurement Phase: Patients provide a blood sample (about 70 mL) to collect white blood cells. This can be done remotely and shipped to Texas Children’s Hospital. The cells are then modified and tested over 4–6 weeks.
Treatment Phase: After completing radiation therapy, patients receive chemotherapy to prepare their bodies for the CAR T cells. The first CAR T cell infusion is given through a peripherally inserted central catheter (PICC line). Depending on the patient’s tumor type, later infusions are given either through the PICC line or directly into the brain fluid using a device called an Ommaya reservoir. The Ommaya reservoir is also used as a safety mechanism to remove cerebrospinal fluid (CSF) in case of increased intracranial pressure. Placement can be arranged at the referral institution or by the Houston team. These infusions are spaced every 4–6 weeks. Each infusion is preceded by standard lymphodepleting chemotherapy with cyclophosphamide and fludarabine.
Patients are monitored closely during and after each infusion. They typically stay in Houston for up to 4 weeks after the first infusion, with shorter stays for future treatments depending on how well they tolerate therapy.
MRIs for disease monitoring can be done at the referring hospital, and patient-reported outcomes are collected at Texas Children’s Hospital.
Eligibility
Ages 12 months to 22 years
Tumor size <5 cm at diagnosis
Adequate organ function
Lansky/Karnofsky >50-60 depending on the tumor type
Low or no steroid dose at time of treatment
Must have completed radiation therapy at least 4 weeks before treatment
Diagnosed with a GD2-positive brain tumor, including:
Newly diagnosed or relapsed DMG (pontine or non-pontine, including spinal cord DMGs before OR after progression) with confirmed H3K27 alteration
Recurrent or progressive high-grade CNS tumors (medulloblastoma, CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas or glioneuronal tumors)
