Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors
St. Jude Children's Research Hospital
Summary
Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed/refractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors. Primary objectives * To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). Secondary objectives * To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed/refractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B). * To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).
Description
Treatment on this study includes four (4) B7-H3-CAR T cell infusions over a 4 week period. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter without lymphodepleting chemotherapy. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells using a 3+3 study design and a 4 week evaluation period. Follow up will occur on this protocol for 1 year after the final B7-H3-CAR T cell infusion and then continue on an institutional long-term follow up protocol to complete 15 years post-infusion.
Eligibility
- Age range
- Up to 21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: Screening Eligibility 1. Age ≤ 21 years of age 2. Primary CNS tumor 3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor 4. For Cohort B, must meet one of the following criteria: * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \[IHC\] or H3K27M mutation if pontine lesion) * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M) * Has presumptive/suspected brainstem high-grade n…
Interventions
- DrugB7-H3-CAR T cells
Autologous T cells transduced with a lentiviral vector expressing a B7-H3-CAR with a CD28z signaling domain and 41BB ligand (B7-H3-CAR T cells). Four (4) infusions of B7-H3-CAR T cells will be locoregionally administered via CNS reservoir catheter.
Location
- St. Jude Children's Research HospitalMemphis, Tennessee