Yoshitaka Narita1, Yoshiki Arakawa2, Fumiyuki Yamasaki3, Ryo Nishikawa4, Tomokazu Aoki5, Masayuki Kanamori6, Motoo Nagane7, Toshihiro Kumabe8, Yuichi Hirose9, Tomotsugu Ichikawa10, Hiroyuki Kobayashi11, Takamitsu Fujimaki12, Hisaharu Goto13, Hideo Takeshima14, Tetsuya Ueba15, Hiroshi Abe16, Takashi Tamiya17, Yukihiko Sonoda18, Atsushi Natsume19, Tatsuyuki Kakuma20, Yasuo Sugita21, Nobukazu Komatsu21, Akira Yamada21, Tetsuro Sasada22, Satoko Matsueda23, Shigeki Shichijo24, Kyogo Itoh24, Mizuhiko Terasaki21. 1. National Cancer Center Hospital, Tokyo, Japan. 2. Kyoto University Graduate School of Medicine, Kyoto, Japan. 3. Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. 4. Saitama Medical University International Medical Center, Saitama, Japan. 5. National Hospital Organization, Kyoto Medical Center, Kyoto, Japan. 6. Tohoku University Graduate School of Medicine, Miyagi, Japan. 7. Kyorin University Faculty of Medicine, Tokyo, Japan. 8. Kitasato University School of Medicine, Kanagawa, Japan. 9. Fujita Health University School of Medicine, Aichi, Japan. 10. Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 11. Hokkaido University Graduate School of Medicine, Hokkaido, Japan. 12. Saitama Medical University Hospital, Saitama, Japan. 13. Yamaguchi University School of Medicine, Yamaguchi, Japan. 14. Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. 15. Kochi Medical School, Kochi, Japan. 16. Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 17. Kagawa University Faculty of Medicine, Kagawa, Japan. 18. Yamagata University Faculty of Medicine, Yamagata, Japan. 19. Nagoya University Graduate School of Medicine, Aichi, Japan. 20. Biostatistics Center, Kurume University, Fukuoka, Japan. 21. Kurume University School of Medicine, Fukuoka, Japan. 22. Cancer Vaccine Center, Kanagawa Cancer Center Research Institute, Kanagawa, Japan. 23. Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York, USA. 24. Cancer Vaccine Center, Kurume University, Fukuoka, Japan.
Abstract
BACKGROUND: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. METHODS: We randomly assigned 88 recurrent glioblastoma patients to receivePPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. RESULTS: Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively. CONCLUSION: This phase III trial met neither the primary nor secondary endpoints.
RCT Entities:
BACKGROUND: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. METHODS: We randomly assigned 88 recurrent glioblastomapatients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. RESULTS: Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPVpatients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPVpatients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPVpatients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively. CONCLUSION: This phase III trial met neither the primary nor secondary endpoints.
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