NCT03500991

HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors

Active, enrolled Phase 1 Last updated 17 December 2025

What this trial tests

Phase 1 trial testing HER2-specific chimeric antigen receptor (CAR) T cell in Central Nervous System Tumor, Pediatric in 10 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

26 July 2018

Primary endpoint
17 January 2024

26 July 2039

Quick facts

Lead sponsor	Seattle Children's Hospital
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	26 July 2018
Primary completion	17 January 2024
Estimated completion	26 July 2039
Sites	1 location across United States

Drugs / interventions tested

• HER2-specific chimeric antigen receptor (CAR) T cell — full drug profile →

Conditions studied

• Central Nervous System Tumor, Pediatric — all drugs for Central Nervous System Tumor, Pediatric →
• Glioma — all drugs for Glioma →
• Ependymoma — all drugs for Ependymoma →
• Medulloblastoma — all drugs for Medulloblastoma →

Sponsor

Seattle Children's Hospital

Who can join

Adults 1 to 26, any sex, with Central Nervous System Tumor, Pediatric or Glioma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.
   Martinez M, Moon EK. · · 2019 · cited 653× · PMID 30804938 · DOI 10.3389/fimmu.2019.00128
2. Brain immunology and immunotherapy in brain tumours.
   Sampson JH, Gunn MD, Fecci PE, Ashley DM. · · 2020 · cited 525× · PMID 31806885 · DOI 10.1038/s41568-019-0224-7
3. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances.
   Maalej KM, Merhi M, Inchakalody VP, Mestiri S, et al · · 2023 · cited 421× · PMID 36717905 · DOI 10.1186/s12943-023-01723-z
4. CAR T cells in solid tumors: challenges and opportunities.
   Marofi F, Motavalli R, Safonov VA, Thangavelu L, et al · · 2021 · cited 394× · PMID 33494834 · DOI 10.1186/s13287-020-02128-1
5. CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?
   Wagner J, Wickman E, DeRenzo C, Gottschalk S. · · 2020 · cited 284× · PMID 32979309 · DOI 10.1016/j.ymthe.2020.09.015
6. Engineered T Cell Therapy for Cancer in the Clinic.
   Zhao L, Cao YJ. · · 2019 · cited 275× · PMID 31681259 · DOI 10.3389/fimmu.2019.02250
7. Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors.
   Theruvath J, Sotillo E, Mount CW, Graef CM, et al · · 2020 · cited 247× · PMID 32341579 · DOI 10.1038/s41591-020-0821-8
8. Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis.
   Vitanza NA, Johnson AJ, Wilson AL, Brown C, et al · · 2021 · cited 239× · PMID 34253928 · DOI 10.1038/s41591-021-01404-8