EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
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ClinicalTrials.gov Identifier: NCT03638167 |
Recruitment Status :
Recruiting
First Posted : August 20, 2018
Last Update Posted : February 25, 2020
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Condition or disease | Intervention/treatment | Phase |
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Central Nervous System Tumor, Pediatric Glioma Ependymoma Medulloblastoma Germ Cell Tumor Atypical Teratoid/Rhabdoid Tumor Primitive Neuroectodermal Tumor Choroid Plexus Carcinoma Pineoblastoma | Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 36 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors |
Actual Study Start Date : | March 19, 2019 |
Estimated Primary Completion Date : | March 2022 |
Estimated Study Completion Date : | March 2037 |

Arm | Intervention/treatment |
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Experimental: ARM A (Tumor Cavity Infusion)
Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity
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Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell
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 |
Experimental: ARM B (Ventricular System Infusion)
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
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 |
- Safety: any adverse events associated with one or multiple EGFR806-specific CAR T cell product infusions will be assessed by CTCAE v5.0. [ Time Frame: up to 6 months ]The type, frequency, severity, and duration of adverse events as a result of EGFR806-specific CAR T cell infusion will be summarized
- Feasibility: The number of successfully manufactured and infused EGFR806-specific CAR T cell product [ Time Frame: 28 days ]The proportion of products successfully manufactured and infused will be measured
- 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 [ Time Frame: up to 6 months ]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.
- 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. [ Time Frame: 28 days ]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
- 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. [ Time Frame: up to 6 months ]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.
- Quantitative biomarker assessment of anti tumor CAR T cell functional activity [ Time Frame: up to 6 months ]The presence of biomarkers of anti-tumor CAR T cell functional activity, such as cytokines, will be quantified via protein expression analysis in CSF. These findings will be correlated with response by disease evaluations via CSF cytology and MRI imaging of the CNS.

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Ages Eligible for Study: | 1 Year to 26 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- First 3 enrolled subjects: age ≥ 15 and ≤ 26 years Subsequent subjects: age ≥ 1 and ≤ 26 years
- Histologically diagnosed EGFR positive Central Nervous System (CNS) tumor
- Evidence of refractory or recurrent CNS disease that has failed first-line 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
- Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
- ≥ 7 days post last chemotherapy administration
- 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy
- No prior virotherapy. Prior genetically modified cell therapy is allowed if not detectable at enrollment.
- Stable or decreasing dosing of steroid treatment for symptomatic relief from CNS disease, with maximum dexamethasone dose of 2.5 mg/m2/day
- Adequate organ function
- Adequate laboratory values
- Subjects of childbearing/fathering potential must agree to use highly effective contraception
- Subject and/or authorized legal representative signed a written consent
Exclusion Criteria:
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03638167
Contact: Juliane Gust, MD, PhD | 206-987-2106 | CBDCIntake@seattlechildrens.org | |
Contact: Nicholas Vitanza, MD | 206-987-2106 | CBDCIntake@seattlechildrens.org |
United States, Washington | |
Seattle Children's Hospital | Recruiting |
Seattle, Washington, United States, 98105 | |
Contact: Juliane Gust, MD, PhD | |
Contact: Nicholas Vitanza, MD | |
Principal Investigator: Juliane Gust, MD, PhD |
Study Chair: | Juliane Gust, MD, PhD | Seattle Children's Hospital |
Responsible Party: | Julie Park, Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital |
ClinicalTrials.gov Identifier: | NCT03638167 |
Other Study ID Numbers: |
BrainChild-02 |
First Posted: | August 20, 2018 Key Record Dates |
Last Update Posted: | February 25, 2020 |
Last Verified: | February 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
CNS, CAR T cell, EGFR-positive pediatric, young adults, brain tumor |
Neoplasms Ependymoma Nervous System Neoplasms Central Nervous System Neoplasms Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Rhabdoid Tumor Pinealoma Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type |
Glioma Neoplasms, Neuroepithelial Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases Neoplasms, Complex and Mixed Brain Neoplasms Brain Diseases Central Nervous System Diseases |