C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)
Diffuse Intrinsic Pontine Glioma, High Grade Glioma, Embryonal Tumor
About this trial
This is an interventional treatment trial for Diffuse Intrinsic Pontine Glioma focused on measuring Gene Therapy, CAR T-cells, chimeric antigen receptor, Brain Cancer, Immunotherapy, Glioma, Brain tumor, DIPG, ETMRs, Medulloepithelioma, Atypical teratoid/rhabdoid tumors
Eligibility Criteria
Procurement Inclusion Criteria:
- Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT
Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with time of diagnosis
- Measurable disease on at least 2 dimensions on MRI
- Age 12 months to 21 years
- Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion
Organ function:
- ANC > 1000 cells/ul
- Platelet count > 100,000 cells/ul
- Total bilirubin < 1.5x ULN
- ALT and AST < 5x ULN
- Serum creatinine or kidney within 2x ULN for age
Procurement Exclusion Criteria:
- Patients who are pregnant or breast feeding
- Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.
Treatment Inclusion Criteria
- Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence OR Recurrent or refractory intracranial embryonal tumor, HGG or ependymal tumor with confirmed GD2-expression (or H3K27M+ for HGG) Examples of embryonal tumors include: medulloblastoma, "PNET", AT/RT
Tumors less than 5 cm in maximum dimension at enrollment
- Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
- Tumors with >25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with time of diagnosis
- Measurable disease on at least 2 dimensions on MRI
- Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed
- Age 12 months to 21 years
- Functional score (Karnofsky/Lansky) ≥ 50
- Completed standard of care radiation therapy. If bevacizumab was administered for management of radiation necrosis, therapy must be completed at least 4 weeks prior to administration of investigational agent.
- Stable neurologic exam for 7 days prior to enrollment
- Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy)
Organ function:
- ANC > 1000 cells/ul
- Platelet count > 100,000 cells/ul
- Total bilirubin < 1.5x ULN
- ALT and AST < 5x ULN
- Serum creatinine or kidney within 2x ULN for age
Treatment Exclusion Criteria
- Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
- Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion
- Patients receiving any concurrent anti-cancer therapy
- Patients who are pregnant or breast feeding
- Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.
Sites / Locations
- Texas Children's HospitalRecruiting
Arms of the Study
Arm 1
Experimental
C7R-GD2.CAR T cells
The dose level for autologous cell C7R-GD2.CART cell immunotherapy administered via intravenous (IV) infusion was determined in the initial phase of the protocol. The IV dosing is 30 million cells/m2 (two equal half-doses of 15 million cells/m2) given at least 5 days and no greater than 10 days apart. Infusion 1 will be given at least 5 days after initial ICV infusion. The second half dose will be given at least 5 days after infusion 1 and will be delayed if CRS or ICANS of Grade 2 or higher is present. In this subsequent phase of the study, the safe dosing levels for autologous cell C7R-GD2.CART cell immunotherapy administered intracerebroventricularly (ICV) via ommaya reservoir or programmable VP shunt in combination with subsequent IV doses will be determined.