دورية أكاديمية
Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial.
| العنوان: | Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial. |
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| المؤلفون: | Thompson EM; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Landi D; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA; Department of Pediatrics, Duke University, Durham, NC, USA., Brown MC; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Friedman HS; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., McLendon R; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA; Department of Pathology, Duke University, Durham, NC, USA., Herndon JE 2nd; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA; Duke Cancer Institute Biostatistics, Duke University, Durham, NC, USA., Buckley E; Duke Cancer Institute Biostatistics, Duke University, Durham, NC, USA., Bolognesi DP; Department of Surgery, Duke University, Durham, NC, USA., Lipp E; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Schroeder K; Department of Pediatrics, Duke University, Durham, NC, USA., Becher OJ; Department of Pediatrics, Mount Sinai Health System, New York, NY, USA., Friedman AH; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., McKay Z; Department of Neurological Surgery, Duke University, Durham, NC, USA., Walter A; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Threatt S; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Jaggers D; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Desjardins A; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Gromeier M; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Bigner DD; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA., Ashley DM; Department of Neurological Surgery, Duke University, Durham, NC, USA; Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA. Electronic address: david.ashley@duke.edu. |
| المصدر: | The Lancet. Child & adolescent health [Lancet Child Adolesc Health] 2023 Jul; Vol. 7 (7), pp. 471-478. Date of Electronic Publication: 2023 Mar 30. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101712925 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-4650 (Electronic) Linking ISSN: 23524642 NLM ISO Abbreviation: Lancet Child Adolesc Health Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, UK] : Elsevier Ltd., [2017]- |
| مواضيع طبية MeSH: | Glioblastoma* , Glioma*/drug therapy , Brain Neoplasms*/therapy , Astrocytoma* , Poliomyelitis* , Cerebellar Neoplasms*, Adult ; Humans ; Child ; Male ; Female ; Adolescent ; Rhinovirus ; Neoplasm Recurrence, Local/therapy ; Immunotherapy |
| مستخلص: | Background: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma. We aimed to assess the safety of lerapolturev when administered as a single dose intracerebrally by convection enhanced delivery in children and young people with recurrent WHO grade 3 or grade 4 glioma, and to assess overall survival in these patients. Methods: This phase 1b trial was done at the Duke University Medical Center (Durham, NC, USA). Patients aged 4-21 years with recurrent high-grade malignant glioma (anaplastic astrocytoma, glioblastoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic pleomorphic xanthoastrocytoma) or anaplastic ependymoma, atypical teratoid rhabdoid tumour, or medulloblastoma with infusible disease were eligible for this study. A catheter was tunnelled beneath the scalp for a distance of at least 5 cm to aid in prevention of infection. The next day, lerapolturev at a dose of 5 × 10 7 median tissue culture infectious dose in 3 mL infusate loaded in a syringe was administered via a pump at a rate of 0·5 mL per h as a one-time dose. The infusion time was approximately 6·5 h to compensate for volume of the tubing. The primary endpoint was the proportion of patients with unacceptable toxic effects during the 14-day period after lerapolturev treatment. The study is registered with ClinicalTrials.gov, NCT03043391. Findings: Between Dec 5, 2017, and May 12, 2021, 12 patients (11 unique patients) were enrolled in the trial. Eight patients were treated with lerapolturev. The median patient age was 16·5 years (IQR 11·0-18·0), five (63%) of eight patients were male and three (38%) were female, and six (75%) of eight patients were White and two (25%) were Black or African American. The median number of previous chemotherapeutic regimens was 3·50 (IQR 1·25-5·00). Six of eight patients had 26 treatment-related adverse events attributable to lerapolturev. There were no irreversible (ie, persisted longer than 2 weeks) treatment-related grade 4 adverse events or deaths. Treatment-related grade 3 adverse events included headaches in two patients and seizure in one patient. Four patients received low-dose bevacizumab on-study for treatment-related peritumoural inflammation or oedema, diagnosed by both clinical symptoms plus fluid-attenuated inversion recovery MRI. The median overall survival was 4·1 months (95% CI 1·2-10·1). One patient remains alive after 22 months. Interpretation: Convection enhanced delivery of lerapolturev is safe enough in the treatment of recurrent paediatric high-grade glioma to proceed to the next phase of trial. Funding: Solving Kids Cancer, B+ Foundation, Musella Foundation, and National Institutes of Health. Competing Interests: Declaration of interests MG, HSF, DPB, AD, DDB, and DMA are equity shareholders of Istari Oncology, the company licensing lerapolturev. MCB, MG, DDB, and DMA own intellectual property licensed to Istari Oncology. MCB, MG, DDB, HSF, and AD received consultancy fees from Istari Oncology. EMT is a scientific consultant for Oncoheroes Biosciences. All other authors declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
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| معلومات مُعتمدة: | K99 CA263021 United States CA NCI NIH HHS; R01 NS108773 United States NS NINDS NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03043391 |
| تواريخ الأحداث: | Date Created: 20230402 Date Completed: 20230626 Latest Revision: 20240702 |
| رمز التحديث: | 20240702 |
| مُعرف محوري في PubMed: | PMC11104482 |
| DOI: | 10.1016/S2352-4642(23)00031-7 |
| PMID: | 37004712 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2352-4650 |
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| DOI: | 10.1016/S2352-4642(23)00031-7 |