NCT04196413

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

Phase 1 Clinical Trial of Autologous GD2 Chimeric Antigen Receptor (CAR) T Cells (GD2CART) for H3K27M-mutant Diffuse Midline Glioma (DMG)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 97 (estimated)
• Sponsor: Stanford University · Academic / Other
• Sex: All
• Age: 2 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The primary purpose of this study is to test whether CAR T cells targeting GD2 (GD2CART) can be successfully made and safely given to children and adults with H3K27M-mutant diffuse midline glioma (DMG). Eligible subjects may have DMG arising in the pons (called difuse intrinisic pontine glioma, DIPG), the spinal cord, or other areas of the brain such as a thalamus

Detailed description

Primary Objectives: * Determine the feasibility of manufacturing autologous T cells transduced with 14g2a-CD8-BBz-iCasp9 retroviral vector expressing GD2 Chimeric Antigen Receptor (GD2CART) for administration in subjects with H3K27M-mutant diffuse midline glioma (DMG) using a retroviral vector and dasatinib in the Miltenyi CliniMACS Prodigy® system. * Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), route and schedule of GD2CART and lymphodepleting chemotherapy in subjects with H3K27M-mutant DMG. * Assess the safety of the MTD/RP2D, route and schedule of GD2CART in expansion cohorts of subjects with H3K27M-mutant DMG. Secondary Objectives: * In a preliminary manner, assess clinical benefit and Patient Reported Outcomes (PROs) of GD2CART at the RP2D in children and adults with H3K27M-mutant DMG. * Evaluate the safety and impact on clinical benefit of repeat intracerebroventricular (ICV) administrations of GD2CART according to Arms A, B, C or D. * If unacceptable toxicity occurs that is possibly, probably or likely related to GD2CART, assess the capacity for AP1903, a dimerizing agent, to mediate clearance of the genetically engineered cells and resolve toxicity.

Conditions

• Glioma of Spinal Cord
• Glioma of Brainstem

Interventions

Type	Name	Description
DRUG	GD2 CAR T cells	Autologous T-Cells transduced with retroviral vector (14g2a-CD8.BB.z.iCasp9) expressing GD2-chimeric antigen receptor
DRUG	Fludarabine	Fludarabine 30 mg/m2 per day IV for days -4, -3, -2
DRUG	Cyclophosphamide	Cyclophosphamide 500 mg/m2 per day IV for days -4, -3, -2
DRUG	Rituximab	First round: 750 mg/m2 per day IV for days -6 and -5. Subsequent rounds: 750 mg/m2 per day IV for day -5.

Timeline

• Start date: 2020-06-04
• Primary completion: 2028-07-31
• Completion: 2043-07-31
• First posted: 2019-12-12
• Last updated: 2026-01-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study