The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.
Name: GD2 CAR T cells
Name: Fludarabine
Name: Cyclophosphamide
Description: The percentage of apheresis samples (fresh or frozen) will be determined for each dose cohort.
Measure: Rate of successful manufacture of GD2.BB.z.iCasp9-CAR T cells using a retroviral vector in the Miltenyi CliniMACS Prodigy system Time: 14 days after apherisDescription: Severity of dose limiting toxicities (DLTs) following chemotherapy and infusion of GD2.BB.z.iCasp9-CAR T cells, will be recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 at each dose level tested in subjects with H3K27M-mutant DIPG and spinal H3K27M-mutant DMG following standard upfront radiation therapy.
Measure: Maximum tolerated dose (MTD)/RP2D of GD2.BB.z.iCasp9-CAR T cells with H3K27M DIPG or spinal H3 K27M-mutant DMG Time: 28 days after infusionDescription: OS is defined as the time from the start of the lymphodepleting chemotherapy preparative regimen to the date of death from any cause
Measure: Overall Survival (OS) Time: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.Description: PFS is defined as the time from the start of the lymphodepleting chemotherapy preparative regimen to the date of radiographic progression or death from any cause.
Measure: Progression-Free Survival (PFS) Time: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.Description: PPS is measured for each subject with DIPG as OS minus PFS, and for each patient with recorded progression as OS minus Time to Progression (TTP)
Measure: Post-progression survival (PPS) Time: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.Description: Radiographic Response will be evaluated using tumor response criteria: Complete Response (CR): disappearance on MR of all evaluable tumor and mass effect; stable or improving neurologic examination. If CSF was positive, it must be negative. Partial Response (PR): ≥ to 50% reduction in tumor size; stable or improving neurologic examination. Stable Disease (SD): at least stable and maintenance corticosteroid dose not increased, and MR/CT imaging meets neither PR nor PD Progressive Disease (PD): Progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression; OR a > 25% increase in the bi-dimensional measurement, OR the appearance of a new tumor lesion.
Measure: Radiographic Response Rate Time: Day 28, 3 months, 6 months, 9 months and 12 months and 24 months post CAR T cell infusion.Description: Resolution of toxicity ≤ grade2, in the event unacceptable toxicity considered possibly, probably or definitely related to GD2.BB.z.iCasp9-CAR T cells within 72 hours
Measure: Measure resolution of toxicity Time: 72 hours of administration of AP1903Allocation: N/A
Single Group Assignment
There is one SNP
The percentage of apheresis samples (fresh or frozen) will be determined for each dose cohort.. Maximum tolerated dose (MTD)/RP2D of GD2.BB.z.iCasp9-CAR T cells with H3K27M DIPG or spinal H3 K27M-mutant DMG. --- K27M ---