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 HER2-specific chimeric antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection cavity or ventricular system in children and young adults with recurrent or refractory HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient meets all other eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meets none of the exclusion criteria, then they can be apheresed, meaning T cells will be collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells. The patient's newly engineered T cells will then be administered via the indwelling CNS catheter for two courses. In the first course they 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. Following the two courses, patient's 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 HER2-specific CAR T cells can be manufactured to complete two courses of treatment with three doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be administered through an indwelling CNS catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study safely can be delivered directly into the brain via indwelling catheter. Secondary aims of the study will include to evaluate 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 time points are available, also evaluate the degree of HER2 expression at diagnosis versus at recurrence.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking all current medications, but you must stop certain treatments like chemotherapy, biologic therapy, and anti-tumor antibody therapy for specific periods before enrolling. Corticosteroid treatment must be stable or decreasing, with a maximum dose specified.
What data supports the effectiveness of the treatment HER2-specific CAR T Cell Locoregional Immunotherapy for pediatric brain cancer?
Research shows that HER2-specific CAR T cells can effectively target and kill HER2-positive medulloblastoma cells in lab tests and animal models, leading to tumor regression. Additionally, early clinical trials in children and young adults with brain tumors suggest that this treatment is well-tolerated and activates a local immune response, indicating potential effectiveness.12345
Is HER2-specific CAR T Cell Therapy safe for children with brain cancer?
How is HER2-specific CAR T Cell Locoregional Immunotherapy different from other treatments for pediatric brain cancer?
This treatment is unique because it involves delivering genetically engineered immune cells (CAR T cells) directly into the brain or spinal fluid, targeting a specific protein (HER2) found on cancer cells. This approach aims to activate a local immune response with potentially fewer side effects compared to traditional treatments like surgery, chemotherapy, and radiation.13478
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 recurrent or refractory HER2-positive CNS tumors who have no standard therapy options left. They must have a CNS catheter in place, a life expectancy of at least 8 weeks, recovered from previous treatments, stable or decreasing steroid use, good organ function and lab values, not be pregnant or breastfeeding, and agree to use contraception.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment Course 1
Participants receive weekly doses of CAR T cells for three weeks, followed by a week off and an examination period
Treatment Course 2
Participants receive another course of weekly doses of CAR T cells for three weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, including MRI evaluations
Extension
Participants may continue receiving additional courses of CAR T cells if no adverse effects are observed and T cells are available
Treatment Details
Interventions
- HER2-specific CAR T Cell Locoregional Immunotherapy
Find a Clinic Near You
Who Is Running the Clinical Trial?
Seattle Children's Hospital
Lead Sponsor