This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells that are lentivirally transduced to express an EGFR806 specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor cavity or the ventricular system in children and young adults with recurrent or refractory EGFR-positive CNS tumors. The primary objectives of this protocol are to evaluate the feasibility, safety, and tolerability of CNS-delivered fractionated CAR T cell infusions employing intra-patient dose escalation. Subjects with supratentorial tumors will receive sequential EGFR806-specific CAR T cells delivered into the tumor resection cavity, subjects with infratentorial tumors will receive sequential CAR T cells delivered into the fourth ventricle, and subjects with leptomeningeal disease will receive sequential CAR T cells delivered into the lateral ventricle. The secondary objectives are to assess CAR T cell distribution within the cerebrospinal fluid (CSF), the extent to which CAR T cells egress into the peripheral circulation, and EGFR expression at recurrence of initially EGFR-positive tumors. Additionally, tumor response will be evaluated by magnetic resonance imaging (MRI) and CSF cytology. The exploratory objectives are to analyze CSF specimens for biomarkers of anti-tumor CAR T cell presence and functional activity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Autologous CD4+ and CD8+ T cells lentivirally transduced to express an EGFR806 specific chimeric antigen receptor (CAR) and EGFRt given via indwelling central nervous system (CNS) catheter
Seattle Children's Hospital
Seattle, Washington, United States
Safety: any adverse events associated with one or multiple EGFR806-specific CAR T cell product infusions will be assessed by CTCAE v5.0.
The type, frequency, severity, and duration of adverse events as a result of EGFR806-specific CAR T cell infusion will be summarized
Time frame: up to 6 months
Feasibility: The number of successfully manufactured and infused EGFR806-specific CAR T cell product
The proportion of products successfully manufactured and infused will be measured
Time frame: 28 days
CAR T cell distribution: The number of subjects with CAR T cell persistence in the cerebrospinal fluid (CSF) and peripheral blood as measured by flow cytometry
The trafficking of the EGFR806-specific CAR T cell product through the CSF by measuring remaining CAR T cells from a prior infusion at the time of each infusion and the trafficking of EGFR806-specific CAR T cells from the CSF into the peripheral blood will be evaluated.
Time frame: up to 6 months
Expression of target epitope: assessment of whether EGFR expression changes in relapsed CNS tumors that were EGFR positive prior to treatment with CAR T cells via immunohistochemistry on resected tissue samples.
The changes in EGFR expression at diagnosis and recurrence of central nervous system (CNS) tumors, if samples from multiple time points is available, will be investigated by evaluating pathology specimens from previous surgeries
Time frame: 28 days
Disease response: Assessment of disease response of EGFR-expressing refractory or recurrent central nervous system (CNS) tumors to EGFR806 specific CAR T cell therapy delivered directly into the CNS by cytology and radiology criteria.
The response of recurrent or refractory central EGFR-expressing CNS tumors to EGFR806-specific CAR T cell therapy delivered directly into the CNS will be determined by evaluating CSF for tumor cells and by CNS imaging with MRIs.
Time frame: up to 6 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.