Central Nervous System Tumor, PediatricPhase 1NCT03638167
EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
A Phase 1 study testing EGFR806-specific chimeric antigen receptor (CAR) T cell in people with Central Nervous System Tumor, Pediatric and Glioma, run by Seattle Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 26 years
- Conditions the study is for
- Central Nervous System Tumor, Pediatric, Glioma, Ependymoma
- What is being tested?
- EGFR806-specific chimeric antigen receptor (CAR) T cell
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Mar 2019to 22 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 26 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
- 3 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors
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
- Being tested
- EGFR806-specific chimeric antigen receptor (CAR) T cell
- Keywords
- CNS, CAR T cell, EGFR-positive, pediatric, young adults, brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Glioma, Ependymoma, Medulloblastoma, Neoplasms, Germ Cell and Embryonal, Rhabdoid Tumor, Neuroectodermal Tumors, Primitive, Choroid Plexus Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EGFR806-specific chimeric antigen receptor (CAR) T cellBiological
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
| Study group | Role | What they receive |
|---|---|---|
| ARM A (Tumor Cavity Infusion) | Experimental | Patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity Receives: 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 Receives: Biological: EGFR806-specific chimeric antigen receptor (CAR) T cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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
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.
Measured: 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
Measured: 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.
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study start19 Mar 2019
- Primary completion22 Dec 2023
- Study completion22 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System Tumor, PediatricStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colleen Annesley, Seattle Children's Hospital
- Investigators
- Juliane Gust, MD, PhD, Study chair, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03638167
- Sponsor's protocol ID
- BrainChild-02
- Status last verified
- Dec 2025
- First submitted
- 15 Aug 2018
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT03638167
- Acronym / sponsor ID
- BrainChild-02
- Conditions
- Central Nervous System Tumor, Pediatric, Glioma, Ependymoma, Medulloblastoma, Germ Cell Tumor, Atypical Teratoid/Rhabdoid Tumor
- Keywords
- CNS, CAR T cell, EGFR-positive, pediatric, young adults, brain tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- 22 Dec 2023 (actual)
- Study completion
- 22 Dec 2023 (actual)
- First posted
- 20 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A (Tumor Cavity Infusion) | Experimental | Biological: EGFR806-specific chimeric antigen receptor (CAR) T cellPatients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity |
| ARM B (Ventricular System Infusion) | Experimental | Biological: EGFR806-specific chimeric antigen receptor (CAR) T cellPatients with either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the fourth ventricle or lateral ventricle, respectively |
Who may qualify
- Ages
- 1 year to 26 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EGFR806-specific chimeric antigen receptor (CAR) T cellAutologous 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 | Biological | ARM A (Tumor Cavity Infusion), ARM B (Ventricular System Infusion) |
Primary outcome
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
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juliane Gust, MD, PhD study chair
Seattle Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EGFR806-specific chimeric antigen receptor (CAR) T cell in people with Central Nervous System Tumor, Pediatric and Glioma, run by Seattle Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.