PDCT-15. Re-MATCH: A PHASE 2 MULTI-INSTITUTIONAL CLINICAL TRIAL OF ADOPTIVE CELLULAR THERAPY FOLLOWING MYELOABLATIVE OR NON-MYELOABLATIVE CHEMOTHERAPY IN CHILDREN AND YOUNG ADULTS WITH RECURRENT MEDULLOBLASTOMA AND PNETs

Abstract

BACKGROUND: Patients with relapsed or progressive medulloblastoma and PNETs (reMB/PNETs) who have failed definitive radiotherapy have a dismal prognosis and no effective salvage treatment regimens. We explored whether adoptive cellular therapy (ACT) following standard myeloablative or nonmyeloablative salvage treatment regimens was feasible, safe, and of potential clinical benefit in children and young adults with reMB/PNETs. METHODS: Pediatric patients and young adults (up to age 30) scheduled for surgical resection or biopsy of first reMB/PNET after having failed definitive cranial radiation therapy +/- spinal radiation were eligible for enrollment. Amplified tumor RNA-pulsed DCs were used to expand tumorspecific lymphocytes ex vivo by co-culture with autologous lymphocytes and IL-2 within our cGMP facility. Patients were enrolled onto one of two treatment arms based on disease staging and eligibility criteria: Group A received induction chemotherapy followed by high-dose chemotherapy and hematopoietic stem cell (HDC+HSC) rescue prior to ACT. Group B received salvage chemotherapy followed by non-meyloablative lymphodepletion with cyclophosphamide and fludarabine followed by ACT. RESULTS: 20 subjects with reMB/PNET have been enrolled on the Re-MATCH protocol. 11 subjects have received ACT, 4 are pending treatment, and 5 were screen failures. There have been no immunotherapy related dose-limiting toxicities. One subject with disseminated (Stage M4) medulloblastoma characterized by leptomeningeal disease, thoracic bony metastasis, and extensive bone marrow infiltration, demonstrated a profound and near complete radiographic and clinical response to treatment. TCR RNA sequencing of peripheral blood lymphocytes has revealed massive clonal expansion of T cells following ACT in this subject. Clinical follow-up is ongoing for primary endpoint analysis of 12-month progression free survival. CONCLUSIONS: Adoptive cellular therapy employing amplified total tumor RNA-pulsed DCs as a platform for expanding tumor-specific lymphocytes is feasible, safe, and potentially effective in patients with recurrent/progressive central PNETs. This study has now progressed to a multi-site investigational phase.