CAR T Cell Therapy for Pediatric Brain Cancer
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before enrolling. You must discontinue chemotherapy, immunotherapy, and radiotherapy, and stabilize or reduce corticosteroid treatment to a specific dose before joining the trial.
What data supports the effectiveness of this treatment for pediatric brain cancer?
Research shows that CAR T cells targeting B7-H3, a protein found on many cancer cells, have shown strong activity against pediatric brain tumors in early studies. In particular, these cells have been effective in animal models of brain tumors, suggesting they could be a promising treatment option.12345
Is CAR T cell therapy safe for children with brain cancer?
CAR T cell therapy has shown some safety in early trials for pediatric brain cancer, with no dose-limiting toxicities reported. However, there were some serious side effects like headache and liver enzyme elevation, and one patient had a catheter-related infection not directly linked to the therapy.12678
How is the treatment SCRI-CARB7H3(s) different from other treatments for pediatric brain cancer?
SCRI-CARB7H3(s) is a unique treatment for pediatric brain cancer because it uses CAR T cells (a type of immune cell modified to attack cancer) that specifically target the B7-H3 protein, which is commonly found on these tumors. Unlike traditional treatments, it is administered directly into the brain, allowing for more effective targeting of the tumor with fewer side effects.123910
Research Team
Rebecca Ronsley, MD
Principal Investigator
Seattle Children's Hospital
Eligibility Criteria
This trial is for children and young adults aged 1 to 26 with specific brain tumors like DIPG, DMG, or other recurrent CNS tumors without standard treatment options. They must be able to undergo apheresis (a procedure to collect T cells), have a catheter in their CNS for drug delivery, expect to live at least 8 weeks, have decent performance status scores (Lansky/Karnofsky ≥60), recovered from prior treatments, stable on low-dose steroids, good organ function and lab values.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive B7H3-specific CAR T cell therapy delivered via an indwelling catheter into the tumor resection cavity or ventricular system. Treatment involves two courses with weekly or bi-weekly dosing depending on the treatment arm.
Follow-up
Participants are monitored for safety and effectiveness after treatment, including MRI evaluations and assessment of CAR T cell distribution and disease response.
Extension
Participants may continue receiving additional courses of CAR T cells if no adverse effects are observed and more T cells are available.
Treatment Details
Interventions
- SCRI-CARB7H3(s)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Seattle Children's Hospital
Lead Sponsor