Locoregional immunotherapy using CAR T cells for pediatric brain tumors

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 study is testing a new type of CAR T cell therapy to see if it can help children with certain hard-to-treat brain tumors feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 1 Year to 26 Years
• Sex: All
• Sponsor: Seattle Children's Hospital (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT05768880 on ClinicalTrials.gov

What this trial studies

This Phase 1 study investigates the use of SC-CAR4BRAIN, a novel CAR T cell therapy, for treating pediatric patients with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory central nervous system tumors. The therapy involves collecting a patient's T cells, bioengineering them to target specific tumor markers (B7-H3, EGFR806, HER2, and IL13-zetakine), and delivering them directly into the ventricular system via an indwelling catheter. Patients will be assigned to treatment arms based on their tumor type, allowing for tailored therapeutic approaches.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 1 to 26 with specific types of CNS tumors that have not responded to standard treatments.

Not a fit: Patients with tumors that are amenable to standard therapies or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for children and young adults with difficult-to-treat brain tumors.

How similar studies have performed: While CAR T cell therapies have shown promise in other cancers, this specific approach for pediatric CNS tumors is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Subjects must be age ≥ 1 and ≤ 26 years (except for the first 3 subjects, who must be age ≥ 12 and ≤ 26 years).
2. Subject disease classified as one of the following:

   1. DIPG at any timepoint following completion of standard radiotherapy
   2. DMG at any timepoint following completion of standard radiotherapy
   3. Evidence of refractory or recurrent CNS disease for which there is no routine therapy, defined by either of the following:

   i. 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
3. Able to tolerate apheresis or already has an apheresis product available for use in manufacturing
4. 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
5. Life expectancy ≥ 8 weeks
6. Lansky or Karnofsky score ≥ 60.
7. 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.
8. Adequate organ function
9. Adequate laboratory values
10. 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

Exclusion Criteria:

1. Presence of ≥ Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention
2. Presence of primary immunodeficiency/bone marrow failure syndrome
3. Presence of clinical and/or radiographic evidence of impending herniation in the CNS
4. For Arm A subjects only: Presence of \> Grade 3 dysphagia
5. Presence of active malignancy other than the CNS tumor under study
6. Presence of active severe infection, defined as either of the following:

   1. Positive blood culture within 48 hours of enrollment, OR
   2. Fever \> 38.2ºC AND clinical signs of infection within 48 hours of enrollment
7. Pregnant or breastfeeding
8. 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
9. Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

Where this trial is running

Seattle, Washington

• Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Rebecca Ronsley, MD — Seattle Children's Hospital
• Study coordinator: Rebecca Ronsley, MD

Conditions Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma; Recurrent CNS Tumor, Adult; Recurrent, CNS Tumor, Childhood; Refractory Primary Malignant Central Nervous System Neoplasm; CNS Tumor; DIPG; DMG