Phase 1 Study of GD2 CAR T Cell Therapy for H3K27M-Mutant Diffuse Midline Glioma in Children and Adults

What this Trial Is About

Researchers are evaluating the use of GD2 chimeric antigen receptor CAR T cells GD2CART in children and adults with H3K27M-mutant diffuse midline glioma DMG, including diffuse intrinsic pontine glioma DIPG and tumors in the spinal cord or other brain regions. This phase 1 clinical trial aims to test whether these specially modified immune cells can be successfully made and safely given to patients with this aggressive brain tumor. The study also seeks to identify the best dose, route, and schedule for administering GD2CART, along with lymphodepleting chemotherapy. Participants receive GD2CART through different methods depending on the study group. Some receive the treatment intravenously after chemotherapy with cyclophosphamide and fludarabine, while others receive it directly into the brains ventricles intracerebroventricularly with or without prior chemotherapy. Dose levels vary by group and are carefully escalated to find the maximum tolerated dose. The chemotherapy regimens may also include rituximab for certain groups. Treatment is given on Day 0 in a hospital setting. Throughout the trial, participants undergo various assessments including safety monitoring up to 28 days after infusion, measurement of successful production of GD2CART cells, and evaluation of tumor response through imaging at multiple time points up to 24 months post-treatment. Researchers also measure overall survival, progression-free survival, and patient-reported outcomes. If serious side effects occur, a special agent AP1903 may be used to clear the engineered cells. The study requires ongoing follow-up and monitoring to assess long-term effects and treatment impact.

GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas (DIPG) & Spinal Diffuse Midline Glioma(DMG)