Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)
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.
⁃ RECIPIENT PROCUREMENT (BLOOD COLLECTION FOR TSA-T MANUFACTURING) INCLUSION CRITERIA
• New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), pineoblastoma, atypical teratoid/rhabdoid tumor, and embryonal tumor, not otherwise specified (NOS).
• \<5 years of age at enrollment.
• Lansky score of ≥60% (see appendix B).
• Organ function:
⁃ ANC ≥750/µL. Absolute lymphocyte count (ALC) \>500/μL. Platelets ≥75K. Bilirubin ≤3xULN. Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) \<5x upper limit of normal (ULN). Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). Pulse oximetry \>90% on room air.
• Parent(s)/guardian(s) capable of providing informed consent.
• Availability of sufficient pre-trial fresh frozen tumor tissue (approximately 50 mg).
• Patient deemed to be of sufficient size to undergo PBMC pheresis for TSA-T generation and PBSC rescue.
• Patient is a surgical candidate for placement of Rickham reservoir in the opinion of a physician.
⁃ RECIPIENT INCLUSION CRITERIA FOR INITIAL TSA-T ADMINISTRATION AND FOR ADDITIONAL INFUSIONS
• Lansky score of ≥60%.
• Organ function:
⁃ Bilirubin ≤3x ULN. AST/ALT ≤5x ULN. Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). Pulse oximetry \>90% on room air.
⁃ \- Neurologic status: Patient must have a stable neurologic exam for 2 weeks, on a stable or decreasing dose of steroids, prior to administration of the first dose of TSA-T cells, and stability for 1 week prior to all subsequent infusions. The exams demonstrating stability must be performed by the study team, although these may occur via telemedicine if necessary. Patient must agree to a brief (\<72 hours) course of steroids