GAIL-B: C7R-GD2.CAR T Cells for Patients with GD2-expressing Brain Tumors
Summary
The study aims to address the lack of standard treatment options for these aggressive brain cancers by combining two promising cancer therapies: antibodies and T cells. Researchers believe that by modifying T cells with a gene that recognizes GD2, a protein found on many cancer cells, and by providing them with a constant supply of cytokine, they can create a more potent and long-lasting anti-cancer therapy.
The study will involve administering infusions of GD2-CAR T cells to patients, both intravenously and directly into the brain. The goal is to determine the optimal dosage and administration method for this novel treatment approach.
Trial Information
Approach
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.
Additional Information
NCT04099797
Full Details on ClinicalTrials.Gov
This trial is only available at Texas Children's Hospital
Official Trial Title
Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients with GD2-expressing Brain Tumors (GAIL-B)
Eligibility
Procurement Inclusion Criteria:
Patients with histologically confirmed, GD2-expressing newly diagnosed DMG (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/DMG except DIPG (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 pre-irradiation MRI.
Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
Measurable disease on at least 2 dimensions on MRI
Age 12 months to 21 years
Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (>60 for cohort 2)
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 DMG (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/DMG except DIPG (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 pre-irradiation MRI
Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
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 (>60 for cohort)
Patients must have completed radiation therapy at least 4 weeks prior to administration of investigational agent. Radiation therapy and (If applicable) bevacizumab treatment for radiation necrosis 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 (it is preferable for patients to stop any concurrent anti-cancer therapy at least three half-lives prior to treatment)
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.
Contact Information
Study Contact: Bilal Omer, MD, Texas Children's Hospital
Phone Number:832-824-6855
Email: bomer@bcm.edu