Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)
Children's National Research Institute
Summary
This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors. Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.
Description
This study will be conducted at Children's National Hospital (CNH) in Washington, DC. TSA-T products will be manufactured at the cell therapy Good Manufacturing Practice (GMP) facility at CNH. Patients enrolled in the study will receive their infusions at CNH. This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA), derived from a patient's primary brain tumor tissues. Participants in this study will receive TSA-T after compl…
Eligibility
- Age range
- 1–30 years
- Sex
- All
- Healthy volunteers
- No
RECIPIENT SCREENING INCLUSION CRITERIA 1. Diagnosis (select one group): * Group A: New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes, pineoblastoma, atypical teratoid/rhabdoid tumor, and embryonal tumor, not otherwise specified (NOS). * Group B: Radiographic evidence consistent with recurrent ependymoma, with planned or recent re-resection. 2. Age: o Group A: \<5 years of age at enrollment o Group B: \>1 year and \<30 years of age at enrollment 3. Tissue: * Group A: Availability of sufficient fresh or frozen tumor tissue (app…
Interventions
- BiologicalMulti-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA)
Participants in this study will receive TSA-T after completion of standard-of-care treatment.
- DrugGroup A Standard-of-Care Backbone Therapy
Patients will undergo surgical resection, then be treated with standard-of-care therapy as required, which may include up to 3 induction chemotherapy cycles (vincristine, cyclophosphamide, cisplatin, etoposide with or without methotrexate) and up to 3 consolidation cycles (carboplatin and thiotepa, each followed by an infusion of autologous peripheral blood stem cells).
- RadiationGroup B Salvage Backbone Therapy
Patients will undergo surgical re-resection - aiming for gross total resection when feasible - followed by re-irradiation. Re-irradiation may be delivered as a conventional fractionated course, hypofractionated stereotactic radiotherapy, or proton therapy.
Location
- Children's National HospitalWashington D.C., District of Columbia