EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors

NCT03638167 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BrainChild-02
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Central Nervous System Tumor, Pediatric; Glioma; Ependymoma; Medulloblastoma; Germ Cell Tumor; Atypical Teratoid/Rhabdoid Tumor; Primitive Neuroectodermal Tumor; Choroid Plexus Carcinoma; Pineoblastoma

Keywords

CNS, CAR T cell, EGFR-positive; pediatric, young adults, brain tumor

Outcome Measures

Primary Outcomes (2)

• 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

  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

  28 days

Secondary Outcomes (3)

• 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

  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.

  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.

  up to 6 months

Other Outcomes (1)

• Quantitative biomarker assessment of anti tumor CAR T cell functional activity

  up to 6 months

Study Arms (2)

ARM A (Tumor Cavity Infusion)

EXPERIMENTAL

Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity

Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell

ARM B (Ventricular System Infusion)

EXPERIMENTAL

Patients with either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the fourth ventricle or lateral ventricle, respectively

Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell

Interventions

EGFR806-specific chimeric antigen receptor (CAR) T cell BIOLOGICAL

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

ARM A (Tumor Cavity Infusion); ARM B (Ventricular System Infusion)

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 15 and ≤ 26 years
• Histologically diagnosed EGFR positive Central Nervous System (CNS) tumor
• Evidence of refractory or recurrent CNS disease for which there is no standard therapy
• Able to tolerate apheresis or apheresis product available for use in manufacturing
• CNS reservoir catheter, such as an Ommaya or Rickham catheter
• Life expectancy ≥ 8 weeks
• Lansky or Karnofsky score ≥ 60
• If patient does not have previously obtained apheresis product, patient must have recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy and discontinue the following prior to enrollment:
• ≥ 7 days post last chemotherapy/biologic therapy administration
• half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy
• Must be at least 30 days from most recent cellular infusion
• All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with maximum dexamethasone dose of 2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed.
• Adequate organ function
• Adequate laboratory values
• Subjects of childbearing/fathering potential must agree to use highly effective contraception

You may not qualify if:

• Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
• Presence of ≥ Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention
• Presence of primary immunodeficiency/bone marrow failure syndrome
• Presence of clinical and/or radiographic evidence of impending herniation
• Presence of active malignancy other than the primary CNS tumor under study
• Presence of active severe infection
• Receiving any anti-cancer agents or chemotherapy
• Pregnant or breastfeeding
• Subject and/or authorized legal representative unwilling to provide consent/assent for participation in the 15 year follow up period
• Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioma; Ependymoma; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Choroid Plexus Carcinoma; Pinealoma; Brain Neoplasms

Interventions

Automobiles

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Study Officials

• Juliane Gust, MD, PhD

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Seattle Children's Therapeutics

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 20, 2018
• Study Start: March 19, 2019
• Primary Completion: December 22, 2023
• Study Completion: December 22, 2023
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)