Locoregional immunotherapy using CAR T cells for pediatric brain tumors
Phase 1 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
This study is testing a new treatment using specially modified immune cells to see if it can help children and young adults with certain types of brain tumors feel better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 90 (estimated) |
| Ages | 1 Year to 26 Years |
| Sex | All |
| Sponsor | Seattle Children's Hospital Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, CAR T, chimeric antigen receptor |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT04185038 on ClinicalTrials.gov |
What this trial studies
This Phase 1 study investigates the use of B7-H3-specific CAR T cells for treating children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory central nervous system tumors. The approach involves collecting the patient's T cells, bioengineering them to target B7-H3-expressing tumor cells, and delivering them directly into the tumor site via a catheter. Patients will be assigned to different treatment arms based on their tumor type and location, allowing for tailored therapy. The study aims to assess the safety and efficacy of this innovative locoregional immunotherapy.
Who should consider this trial
Good fit: Ideal candidates include children and young adults aged 1 to 26 with recurrent or refractory CNS tumors or those diagnosed with DIPG or DMG.
Not a fit: Patients with tumors that are not B7-H3 expressing or those who do not meet the eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for pediatric patients with aggressive brain tumors that currently have limited effective therapies.
How similar studies have performed: While CAR T cell therapies have shown promise in other cancers, this specific approach targeting B7-H3 in pediatric brain tumors is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Age ≥ 1 and ≤ 26 years 2. 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 3. Able to tolerate apheresis, or has apheresis product available for use in manufacturing 4. CNS reservoir catheter, such as an Ommaya or Rickham catheter 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: 1. ≥ 7 days post last chemotherapy/biologic therapy administration 2. 3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy 3. Must be at least 30 days from most recent cellular infusion 4. 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. Patients of childbearing/fathering potential must agree to use highly effective contraception 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 4. Presence of \>Grade 3 dysphagia 5. Presence of active malignancy other than the primary CNS tumor under study 6. Presence of active severe infection 7. Receiving any anti-cancer agents or chemotherapy 8. Pregnant or breastfeeding 9. Subject and/or authorized legal representative unwilling or unable to provide consent/assent for participation in the 15 year follow up period 10. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
Where this trial is running
Seattle, Washington
- Seattle Children's Hospital — Seattle, Washington, United States (Recruiting)
Study contacts
- Study coordinator: Rebecca Ronsley, MD
- Email: CBDCIntake@seattlechildrens.org
- Phone: 206-987-2106
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.