Central Nervous System Tumor, PediatricPhase 1NCT03500991
HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
A Phase 1 study testing HER2-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 lentivirally transduced to express a HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and… 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?
- HER2-specific chimeric antigen receptor (CAR) T cell
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2018to 26 Jul 2039
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 ≥ 1 and ≤ 26 years
- Histologically diagnosed HER2-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 has 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 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 cell 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
- Patients 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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- Pregnant or breastfeeding
- Subject and/or authorized legal representative unwilling or unable 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 HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2 Positive Recurrent/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 lentivirally transduced to express a HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and young adults with recurrent or refractory HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient meets all other eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meets none of the exclusion criteria, then they can be apheresed, meaning T cells will be collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells. The patient's newly engineered T cells will then be administered via the indwelling CNS catheter for two courses. In the first course they will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Following the two courses, patient's will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available.
The hypothesis is that an adequate amount of HER2-specific CAR T cells can be manufactured to complete two courses of treatment with three doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be administered through an indwelling CNS catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study safely can be delivered directly into the brain via indwelling catheter. Secondary aims of the study will include to evaluate CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple time points are available, also evaluate the degree of HER2 expression at diagnosis versus at recurrence.
- Conditions
- Central Nervous System Tumor, Pediatric, Glioma, Ependymoma, Medulloblastoma, Germ Cell Tumor, Atypical Teratoid/Rhabdoid Tumor
- Being tested
- HER2-specific chimeric antigen receptor (CAR) T cell
- Keywords
- CNS, CAR T cell, HER2-positive, brain tumor, pediatric, young adults
- 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.
HER2-specific chimeric antigen receptor (CAR) T cellBiological
Autologous CD4 and CD8 T cells lentivirally transduced to express a HER2 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
Intervention: HER2-specific chimeric antigen receptor (CAR) T cell Receives: Biological: HER2-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
Intervention: HER2-specific chimeric antigen receptor (CAR) T cell Receives: Biological: HER2-specific chimeric antigen receptor (CAR) T cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish the safety, defined by the adverse events, of HER2-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system
The type, frequency, severity, and duration of adverse events as a result of HER2-specific CAR T cell infusion will be summarized
Measured: up to 6 months
Establish the feasibility, defined by the ability to produce and administer CAR T cell product, of HER2-specific CAR T cell product infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system
The proportion of products successfully manufactured and infused will be measured
Measured: 28 days
Secondary outcomes (3)
Assess the distribution of CNS-delivered HER2-specific CAR T cells within the cerebrospinal fluid (CSF) and peripheral blood
The trafficking of HER2-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 HER2-specific CAR T cells from the CSF into the peripheral blood will be evaluated
Measured: up to 6 months
Assessment of whether HER2 expression changes in relapsed CNS tumors that were HER2 positive prior to treatment with CAR T cells
The changes in HER2 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
Assessment of disease response of HER2-expressing refractory or recurrent central nervous system (CNS) tumors to HER2 specific CAR T cell therapy delivered directly into the CNS
The response of recurrent or refractory central HER2-expressing CNS tumors to HER2-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 posted18 Apr 2018
- Study start26 Jul 2018
- Primary completion17 Jan 2024
- Study completion26 Jul 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- 10 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
- Rebecca Ronsley, MD, Study chair, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500991
- Sponsor's protocol ID
- BrainChild-01
- Status last verified
- Dec 2025
- First submitted
- 21 Mar 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
Publications
Li X, Li W, Xu L, Song Y. Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments. Chin Med J (Engl). 2024 Jun 5;137(11):1285-1302. doi: 10.1097/CM9.0000000000002818. Epub 2023 Aug 28.
PubMed 37640679Vitanza NA, Johnson AJ, Wilson AL, Brown C, Yokoyama JK, Kunkele A, Chang CA, Rawlings-Rhea S, Huang W, Seidel K, Albert CM, Pinto N, Gust J, Finn LS, Ojemann JG, Wright J, Orentas RJ, Baldwin M, Gardner RA, Jensen MC, Park JR. Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis. Nat Med. 2021 Sep;27(9):1544-1552. doi: 10.1038/s41591-021-01404-8. Epub 2021 Jul 12.
PubMed 34253928
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 HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2 Positive Recurrent/Refractory Pediatric Central Nervous System Tumors
- ClinicalTrials.gov ID
- NCT03500991
- Acronym / sponsor ID
- BrainChild-01
- Conditions
- Central Nervous System Tumor, Pediatric, Glioma, Ependymoma, Medulloblastoma, Germ Cell Tumor, Atypical Teratoid/Rhabdoid Tumor
- Keywords
- CNS, CAR T cell, HER2-positive, brain tumor, pediatric, young adults
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Study start
- 26 Jul 2018 (actual)
- Primary completion
- 17 Jan 2024 (actual)
- Study completion
- 26 Jul 2039 (estimated)
- First posted
- 18 Apr 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 lentivirally transduced to express a HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and young adults with recurrent or refractory HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient meets all other eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meets none of the exclusion criteria, then they can be apheresed, meaning T cells will be collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells. The patient's newly engineered T cells will then be administered via the indwelling CNS catheter for two courses. In the first course they will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Following the two courses, patient's will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving additional courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available.
The hypothesis is that an adequate amount of HER2-specific CAR T cells can be manufactured to complete two courses of treatment with three doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be administered through an indwelling CNS catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study safely can be delivered directly into the brain via indwelling catheter. Secondary aims of the study will include to evaluate CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple time points are available, also evaluate the degree of HER2 expression at diagnosis versus at recurrence.
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: HER2-specific chimeric antigen receptor (CAR) T cellpatients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity Intervention: HER2-specific chimeric antigen receptor (CAR) T cell |
| ARM B (Ventricular System Infusion) | Experimental | Biological: HER2-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 Intervention: HER2-specific chimeric antigen receptor (CAR) T cell |
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 ≥ 1 and ≤ 26 years
- Histologically diagnosed HER2-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 has apheresis product available for use in manufacturing
- CNS reservoir catheter, such as an Ommaya or Rickham catheter
Key exclusion criteria (9 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 |
|---|---|---|
| HER2-specific chimeric antigen receptor (CAR) T cellAutologous CD4 and CD8 T cells lentivirally transduced to express a HER2 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
Establish the safety, defined by the adverse events, of HER2-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system
Time frame: up to 6 months
The type, frequency, severity, and duration of adverse events as a result of HER2-specific CAR T cell infusion will be summarized
Establish the feasibility, defined by the ability to produce and administer CAR T cell product, of HER2-specific CAR T cell product infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system
Time frame: 28 days
The proportion of products successfully manufactured and infused will be measured
3 secondary outcomes
Assess the distribution of CNS-delivered HER2-specific CAR T cells within the cerebrospinal fluid (CSF) and peripheral blood
Time frame: up to 6 months
Assessment of whether HER2 expression changes in relapsed CNS tumors that were HER2 positive prior to treatment with CAR T cells
Time frame: 28 days
Assessment of disease response of HER2-expressing refractory or recurrent central nervous system (CNS) tumors to HER2 specific CAR T cell therapy delivered directly into the CNS
Time frame: up to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Derived from this study: PubMed 37640679Li X, Li W, Xu L, Song Y. Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments. Chin Med J (Engl). 2024 Jun 5;137(11):1285-1302. doi: 10.1097/CM9.0000000000002818. Epub 2023 Aug 28.
- Derived from this study: PubMed 34253928Vitanza NA, Johnson AJ, Wilson AL, Brown C, Yokoyama JK, Kunkele A, Chang CA, Rawlings-Rhea S, Huang W, Seidel K, Albert CM, Pinto N, Gust J, Finn LS, Ojemann JG, Wright J, Orentas RJ, Baldwin M, Gardner RA, Jensen MC, Park JR. Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis. Nat Med. 2021 Sep;27(9):1544-1552. doi: 10.1038/s41591-021-01404-8. Epub 2021 Jul 12.
- 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.
Rebecca Ronsley, MD 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 HER2-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 9 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: under way, not looking for participants, 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?
This study is still under way. Results are not available in the source record yet.
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?
Establish the safety, defined by the adverse events, of HER2-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system (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?
On the ClinicalTrials.gov record for NCT03500991, which also lists 2 linked publications.
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.