CTIM-21. PEPTIDE VACCINE DIRECTED TO CMV pp65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL
| Autor: | John Sampson, James E. Herndon, Katherine B. Peters, Kristin Schroeder, Denise Jaggers, Eric S. Lipp, Gerald E. Archer, Duane Michell, Charlene Flahiff, Annick Desjardins, Ashley Walter, Bea Balajonda, Daniel Landi, Mustafa Khasraw, Bridget Archambault, Eric M. Thompson, Michael D. Malinzak, David M. Ashley, Evan Buckley, Margaret Johnson, Dina Randazzo |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Medulloblastoma Cancer Research medicine.medical_specialty Temozolomide Diphtheria vaccine business.industry medicine.disease Clinical Trials: Immunologic Vaccination Aldesleukin Internal medicine Glioma medicine Peptide vaccine AcademicSubjects/MED00300 AcademicSubjects/MED00310 Neurology (clinical) business medicine.drug Anaplastic astrocytoma |
| Zdroj: | Neuro-Oncology |
| ISSN: | 1523-5866 1522-8517 0329-9309 |
| DOI: | 10.1093/neuonc/noaa215.155 |
| Popis: | INTRODUCTION The cytomegalovirus (CMV) antigen, pp65, is ubiquitously expressed in malignant glioma and medulloblastoma but not in healthy brain. The objective of this Phase I trial (NCT03299309) was to assess the safety and feasibility of a novel pp65 peptide vaccine (PEP-CMV) in children and young adults with recurrent medulloblastoma and malignant glioma. METHODS Vaccines contain a synthetic long peptide (SLP) of 26 amino acids encoding multiple potential class I, class II, and antibody epitopes of CMV pp65 across several haplotypes. This SLP is administered as an emulsion in Montanide ISA 51. Patients receive a single course of temozolomide to induce lymphopenia, tetanus/diphtheria toxoid site preconditioning, then vaccines administered intradermally every two weeks for 3 doses, then monthly. RESULTS To date, 17 patients have been enrolled. Diagnoses include medulloblastoma (n=1), glioblastoma (n=9), anaplastic oligodendroglioma (n=2), anaplastic astrocytoma (n=2), and malignant glioma NOS (n=3). Mean number of prior treatment regimens is 4.9 (range 1–12). Mean age is 22yo (range 6–35) and 41% of patients are male. The median KPS is 80. The median number of vaccines given at time of analysis is 3.3 (range 1–12). There have been no ≥ 3 Grade toxicities related to the vaccine. One patient developed nausea, vomiting, palpitations, and tachycardia after vaccination and had elevated inflammatory cytokines consistent with cytokine release syndrome. Median PFS is 2.5 months (95% CI: 0.8, not estimable) and median OS is 6.5 months (95% CI 1.8, not estimable). Interim analysis of immune monitoring bloodwork and perfusion MRI to quantify responses to PEP-CMV has been delayed due to COVID-19. However, adults with GBM who received PEP-CMV (NCT02864368) had significant (p≤0.05) increases in GCSF, GM-CSF, IFN-γ, IL-10, IL-2, IL-8, MIP1-α, and TNF-α levels. CONCLUSIONS Preliminary results demonstrate that PEP-CMV is feasible and well-tolerated in heavily pretreated, multiply recurrent patients. |
| Databáze: | OpenAIRE |
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