Diffuse Intrinsic Pontine GliomaPhase 1NCT05768880
Study of B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
A Phase 1 study testing SC-CAR4BRAIN in people with Diffuse Intrinsic Pontine Glioma and Diffuse Midline 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 SC-CAR4BRAIN, an autologous CD4+ and CD8+ T cells lentivirally transduced to express to express combinations of B7-H3, EGFR806, HER2, and IL13-zetakine chimeric antigen receptors (CAR). Read more about this study
- Who is it for?
- Ages 1 year to 26 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, Recurrent CNS Tumor, Adult
- What is being tested?
- SC-CAR4BRAIN
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2023to 31 Dec 2043
- Phase
- Phase 1
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
- Subjects must be age ≥ 1 and ≤ 26 years (except for the first 3 subjects, who must be age ≥ 12 and ≤ 26 years).
- Subject disease classified as one of the following:
- DIPG at any timepoint following completion of standard radiotherapy
- DMG at any timepoint following completion of standard radiotherapy
- Evidence of refractory or recurrent CNS disease for which there is no routine therapy, defined by either of the following:
- New site or sites of measurable or evaluable disease by radiographic imaging or histologic confirmation following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable, OR ii. Measurable or evaluable disease that persists following completion of routine care first-line therapy for which curative salvage therapy is not available or amenable
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- Able to tolerate apheresis or already has an apheresis product available for use in manufacturing
- CNS reservoir catheter, such as an Ommaya or Rickham catheter, present in the proper location for CNS-directed therapy delivered as specified for BrainChild-04
- Life expectancy ≥ 8 weeks
- Lansky or Karnofsky score ≥ 60.
- If patient does not have previously obtained apheresis product, patient must have discontinued, and 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 from the time of enrollment through 12 months following the last T cell infusion
Who cannot join
- 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 in the CNS
- For Arm A subjects only: Presence of > Grade 3 dysphagia
- Presence of active malignancy other than the CNS tumor under study
- Presence of active severe infection, defined as either of the following:
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- Positive blood culture within 48 hours of enrollment, OR
- Fever > 38.2ºC AND clinical signs of infection within 48 hours of enrollment
- Pregnant or breastfeeding
- Subject and/or authorized legal representative unwilling to provide consent/assent for study participation, including participation in the 15-year follow-up period, which is required if CAR T cell therapy is administered
- Presence of any condition that, in the opinion of the investigator, would prohibit the subject 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 B7-H3, EGFR806, HER2, And IL13-Zetakine (Quad) CAR T Cell Locoregional Immunotherapy For Pediatric Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, And Recurrent Or Refractory Central Nervous System Tumors
This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with SC-CAR4BRAIN, an autologous CD4+ and CD8+ T cells lentivirally transduced to express to express combinations of B7-H3, EGFR806, HER2, and IL13-zetakine chimeric antigen receptors (CAR). CAR T cells are delivered via an indwelling catheter into the ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors.
A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into their ventricular system, and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that target B7H3, EGFR806, HER2, and IL13-zetakine on tumor cells.
Read more
Patients will be assigned to 1 of 2 treatment Arms based on the type of their tumor:
- Arm A is for patients with DIPG (meaning primary disease localized to the pons, metastatic disease is allowed) anytime after standard radiation OR after progression.
- Arm B is for patients with non-pontine DMG (meaning DMG in other parts of the brain such as the thalamus or spine) anytime after standard radiation OR after progression. This Arm also includes other recurrent/refractory CNS tumors.
- Conditions
- Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, Recurrent CNS Tumor, Adult, Recurrent, CNS Tumor, Childhood, Refractory Primary Malignant Central Nervous System Neoplasm
- Being tested
- SC-CAR4BRAIN
- Keywords
- CNS Tumor, DIPG, DMG, B7-H3, HER2, IL13-zetakine, EGFR806, CAR T cell, pediatric, brain tumor
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Central Nervous System Neoplasms, Recurrence, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SC-CAR4BRAINBiological
Courses of weekly intraventricular CNS administered SC-CAR4BRAIN infusions for 3 weeks, then 1 week off
| Study group | Role | What they receive |
|---|---|---|
| Arm A - DIPG | Experimental | Not described Receives: Biological: SC-CAR4BRAIN |
| Arm B - DMG & recurrent/refractory tumors | Experimental | Not described Receives: Biological: SC-CAR4BRAIN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Manufacturing Feasibility
Number and percent of subjects with sufficient therapeutic product generated to receive two courses on the intended dose regimen
Measured: 42 days
Safety of SC-CAR4BRAIN
Establish the safety, defined by the adverse events of fractionated intraventricular CNS administration of adoptive therapy with SC-CAR4BRAIN in children and young adults with DIPG, DMG, or recurrent/refractory CNS tumors
Measured: 28 days post-final SC-CAR4BRAIN infusion
Dose level
Establish the maximally tolerated dose regimen (MTDR) and recommended Phase 2 dose regimen (RP2DR) of fractionated intraventricular CNS administered SC CAR4BRAIN infusions.
Measured: 28 days
Administration feasibility
Number of subjects meeting criteria for their initial CAR T infusion and number of subjects meeting criteria for at least 2 courses of CAR T infusions
Measured: 98 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2023
- Study start5 May 2023
- Primary completion15 Jan 2028 (estimated)
- Study completion31 Dec 2043 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies of the same condition, open and under way.
- 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
- 72 participants (estimated)
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 HospitalRebecca Ronsley, MD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05768880
- Sponsor's protocol ID
- BrainChild-04
- Status last verified
- Oct 2026
- First submitted
- 17 Feb 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No