Children's National Research Institute
This is an open-label phase 1 safety and feasibility study evaluating a novel combination therapy for Diffuse Midline Glioma (DMG), an aggressive brain tumor with a very poor prognosis - an average one-year overall survival. This study combines blood-brain barrier (BBB) disruption (BBBD) using low-intensity focused ultrasound (LIFU) and microbubble treatment, and intravenous infusion of autologous, tumor multi-antigen associated specific cytotoxic T lymphocyte (TAA-T) therapy. The TAA-T cell investigational product in this protocol is manufactured to target Preferentially Expressed Antigen of Melanoma (PRAME), Wilms Tumor 1 (WT1), and survivin.
This is an open-label phase 1 safety and feasibility study evaluating a novel combination therapy for Diffuse Midline Glioma (DMG), studying blood-brain barrier disruption (BBBD) which is accomplished by utilizing the Exablate 4000 Type 2 system consisting of low intensity focused ultrasound (LIFU) paired with microbubbles. The term "microbubbles" refers specifically to DEFINITY® (perflutren lipid microsphere), an FDA-approved ultrasound contrast agent. In this study, however, DEFINITY® is being used as a mechanical resonator, and is investigational in this context. BBBD will be combined with…
Inclusion Criteria: Inclusion Criteria for Screening and Procurement: * Age ≥ 3 and ≤ 25 years * Diagnosis of pontine or thalamic DMG * Group A: newly diagnosed pontine DMG after completion of standard radiation therapy; radiographic diagnosis is defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons - tissue diagnosis is not required * Group B: newly diagnosed thalamic DMG after completion of standard radiation therapy; tissue diagnosis is required NOTE: Tumor extending outside of the pons or the thalamus can remain eligible if the LIFU treatment is no…
Intravenous tumor associated antigen specific T cell (TAA-T) infusion.
BBB disruption using the Exablate 4000 Type 2 System with DEFINITY microbubbles.