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

Launched by SEATTLE CHILDREN'S HOSPITAL · Dec 2, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach using modified immune cells, called CAR T cells, to help fight certain types of brain tumors in children and young adults. Specifically, it focuses on tumors like diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and other recurrent or hard-to-treat central nervous system tumors. The CAR T cells are engineered to target a protein called B7-H3, which is found on some tumor cells. The treatment involves placing a special catheter into the brain so that these engineered cells can be delivered directly to the tumor site. Participants will receive two courses of treatment, with doses given weekly for three weeks, followed by rest and evaluation periods.

To be eligible for this trial, patients need to be between the ages of 1 and 26 and have a specific type of brain tumor that is either recurrent or has not responded to standard therapies. They should also have a catheter already placed in their brain and be in reasonably good health. Throughout the trial, doctors will closely monitor the patients' responses to the treatment using scans and tests. This study aims to see if these modified cells can effectively reach and attack the tumors while being safely administered through the catheter. It's an exciting opportunity for eligible patients to access a potentially promising new treatment option.

Gender

ALL

Eligibility 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