Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

NCT04185038 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BrainChild-03
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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 B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or 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 the tumor resection cavity or 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 targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B 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. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms 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 B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating 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 timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma; Ependymoma; Medulloblastoma, Childhood; Germ Cell Tumor; Atypical Teratoid/Rhabdoid Tumor; Primitive Neuroectodermal Tumor; Choroid Plexus Carcinoma; Pineoblastoma, Childhood; Glioma; Central Nervous System Tumor

Keywords

CNS, CAR T cell, B7-H3, pediatric, young adult, brain tumor, DIPG, DMG

Outcome Measures

Primary Outcomes (2)

• Establish the safety, defined by the adverse events, of B7H3-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 B7H3-specific CAR T cell infusion will be summarized

  up to 7 months

• Establish the feasibility, defined by the ability to produce and administer CAR T cell product, of B7H3-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

  28 days

Secondary Outcomes (3)

• Assess the distribution of CNS-delivered B7H3-specific CAR T cells distribution within the cerebrospinal fluid (CSF) and peripheral blood

  up to 6 months

• Assessment of disease response of B7H3-expressing DIPG and DMG tumors to B7H3 specific CAR T cell therapy delivered into the CNS

  up to 6 months

• Assessment of disease response of B7H3-expressing refractory or recurrent central nervous system (CNS) tumors to B7H3 specific CAR T cell therapy delivered into the tumor cavity or into the CNS

  up to 6 months

Other Outcomes (1)

• Quantitative biomarker assessment of anti tumor CAR T cell functional activity

  up to 6 months

Study Arms (5)

ARM A (Tumor Cavity Infusion) - [CLOSED TO ENROLLMENT]

EXPERIMENTAL

Patients with non-DIPG supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity

Biological: SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

ARM B (Ventricular System Infusion) - [CLOSED TO ENROLLMENT]

EXPERIMENTAL

Patients with non-DIPG either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the ventricular system

Biological: SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

ARM C (DIPG) - [CLOSED TO ENROLLMENT]

EXPERIMENTAL

Patients with DIPG for whom CAR T cells will be delivered into the ventricular system

Biological: SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

Arm D (Non-pontine DMG)

EXPERIMENTAL

Patients with non-pontine DMG for whom CAR T cells will be delivered into the ventricular system

Biological: SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

Arm E

EXPERIMENTAL

Patients with DIPG who will receive up to 15 doses of CAR T cells delivered into the ventricular system

Biological: SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel

Interventions

SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel BIOLOGICAL

Autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3 specific chimeric antigen receptor (CAR) and EGFRt given via indwelling central nervous system (CNS) catheter

ARM A (Tumor Cavity Infusion) - [CLOSED TO ENROLLMENT]; ARM B (Ventricular System Infusion) - [CLOSED TO ENROLLMENT]; ARM C (DIPG) - [CLOSED TO ENROLLMENT]; Arm D (Non-pontine DMG); Arm E

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 1 and ≤ 26 years
• Diagnosis of refractory or recurrent CNS disease for which there is no standard therapy, or diagnosis of DIPG or DMG at any time point following completion of 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
• 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
• 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
• Patients of childbearing/fathering potential must agree to use highly effective contraception

You may not qualify if:

• 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 \>Grade 3 dysphagia
• 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 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

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Related Publications (3)

• Ronsley R, Choe M, Wright J, Seidel K, Lee A, Wendler J, Annesley C, Jensen MC, Park JR, Vitanza NA, Gust J. Tumor inflammation-associated neurotoxicity in children with diffuse intrinsic pontine glioma receiving B7-H3-targeting CAR T cells on BrainChild-03. Neurooncol Pract. 2025 Aug 3;13(1):105-111. doi: 10.1093/nop/npaf080. eCollection 2026 Feb.

  PMID: 41798119 DERIVED

• Vitanza NA, Ronsley R, Choe M, Seidel K, Huang W, Rawlings-Rhea SD, Beam M, Steinmetzer L, Wilson AL, Brown C, Beebe A, Lindgren C, Gustafson JA, Wein A, Holtzclaw S, Hoeppner C, Goldstein HE, Browd SR, Hauptman JS, Lee A, Ojemann JG, Crotty EE, Leary SES, Perez FA, Wright JN, Alonso MM, Dun MD, Foster JB, Hurst D, Kong A, Thomsen A, Orentas RJ, Albert CM, Pinto N, Annesley C, Gardner RA, Ho O, Pattabhi S, Gust J, Wendler JP, Park JR, Jensen MC. Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial. Nat Med. 2025 Mar;31(3):861-868. doi: 10.1038/s41591-024-03451-3. Epub 2025 Jan 7.

  PMID: 39775044 DERIVED

• Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121.

  PMID: 35468680 DERIVED

Related Links

• BrainChild-03 Expanded Access Policy

MeSH Terms

Conditions

Central Nervous System Neoplasms; Diffuse Intrinsic Pontine Glioma; Ependymoma; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Choroid Plexus Carcinoma; Pinealoma; Glioma; Brain Neoplasms

Interventions

Automobiles

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Diseases; Central Nervous System Diseases; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Motor Vehicles; Transportation; Technology, Industry, and Agriculture

Study Officials

• Rebecca Ronsley, MD

  Seattle Children's Hospital

  STUDY CHAIR

Central Study Contacts

Rebecca Ronsley, MD

CONTACT

206-987-2106; CBDCIntake@seattlechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Immunotherapy

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: December 4, 2019
• Study Start: December 11, 2019
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2042
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)