dc.contributor.author | Schuelke, MR | |
dc.contributor.author | Gundelach, JH | |
dc.contributor.author | Coffey, M | |
dc.contributor.author | West, E | |
dc.contributor.author | Scott, K | |
dc.contributor.author | Johnson, DR | |
dc.contributor.author | Samson, A | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Vile, RG | |
dc.contributor.author | Bram, RJ | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-09-06T11:38:57Z | |
dc.date.available | 2022-09-06T11:38:57Z | |
dc.date.issued | 2022-01-01 | |
dc.identifier | vdac085 | |
dc.identifier.citation | Neuro-Oncology Advances, 2022, 4 (1), pp. vdac085 - | |
dc.identifier.issn | 2632-2498 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5417 | |
dc.identifier.eissn | 2632-2498 | |
dc.identifier.eissn | 2632-2498 | |
dc.identifier.doi | 10.1093/noajnl/vdac085 | |
dc.description.abstract | BACKGROUND: Brain tumors are the leading cause of cancer death for pediatric patients. Pelareorep, an immunomodulatory oncolytic reovirus, has intravenous efficacy in preclinical glioma models when preconditioned with GM-CSF (sargramostim). We report a phase I trial with the primary goal of evaluating the safety of sargramostim/pelareorep in pediatric patients with recurrent or refractory high-grade brain tumors and a secondary goal of characterizing immunologic responses. METHODS: The trial was open to pediatric patients with recurrent or refractory high-grade brain tumors (3 + 3 cohort design). Each cycle included 3 days of subcutaneous sargramostim followed by 2 days of intravenous pelareorep. Laboratory studies and imaging were acquired upon recruitment and periodically thereafter. RESULTS: Six patients participated, including three glioblastoma, two diffuse intrinsic pontine glioma, and one medulloblastoma. Two pelareorep dose levels of 3 × 108 and 5 × 108 tissue culture infectious dose 50 (TCID50) were assessed. One patient experienced a dose limiting toxicity of persistent hyponatremia. Common low-grade (1 or 2) adverse events included transient fatigue, hypocalcemia, fever, flu-like symptoms, thrombocytopenia, and leukopenia. High-grade (3 or 4) adverse events included neutropenia, lymphopenia, leukopenia, hypophosphatemia, depressed level of consciousness, and confusion. All patients progressed on therapy after a median of 32.5 days and died a median of 108 days after recruitment. Imaging at progression did not show evidence of pseudoprogression or inflammation. Correlative assays revealed transient but consistent changes in immune cells across patients. CONCLUSIONS: Sargramostim/pelareorep was administered to pediatric patients with recurrent or refractory high-grade brain tumors. Hyponatremia was the only dose limiting toxicity (DLT), though maximum tolerated dose (MTD) was not determined. | |
dc.format | Electronic-eCollection | |
dc.format.extent | vdac085 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.relation.ispartof | Neuro-Oncology Advances | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
dc.subject | oncolytic virotherapy | |
dc.subject | pediatric brain tumors | |
dc.subject | reovirus | |
dc.subject | sargramostim | |
dc.title | Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-01-01 | |
dc.date.updated | 2022-09-06T11:37:26Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1093/noajnl/vdac085 | |
rioxxterms.licenseref.startdate | 2022-01-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35821679 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1093/noajnl/vdac085 | |
pubs.volume | 4 | |
icr.researchteam | Trans Immunotherapy | |
dc.contributor.icrauthor | Melcher, Alan | |
icr.provenance | Deposited by Mr Arek Surman on 2022-09-06. Deposit type is initial. No. of files: 1. Files: Phase I trial of sargramostimpelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors.pdf | |