Yoshihiro Muragaki1,2,3 #, Eiichi Ishikawa4 #, Manabu Tamura2,3, Takakazu Kawamata2, Masahiko Gosho5, Koichi Hashimoto6, Takashi Komori7, Hideaki Yokoo8, Masao Matsutani9, Katsuya Maebayashi10, Toshihide Tanaka11, Shigeru Yamaguchi12, Masayuki Kanamori13, Tetsuya Yamamoto14, Mitsuto Hanihara15, Yoshiki Arakawa16, Takashi Sasayama17, Tatsuya Abe18, Hideo Nakamura19, Akifumi Mukasa20, Takeo Uzuka21, Kosuke Nakajo22, Tadao Ohno23. A randomized, placebo-controlled phase III trial of an autologous, formalin-fixed tumor vaccine for newly diagnosed glioblastoma: Trial Protocol. Japanese Journal of Clinical Oncology, 2025, 1–7. https://doi.org/10.1093/jjco/hyaf078
1 Department of Medical Device Engineering, Kobe University, Kusunoki-cho, Chuo-ku, Kobe City, Hyogo 650-0017, Japan
2 Department of Neurosurgery, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
3 Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
4 Department of Neurosurgery, University of Tsukuba, Tennodai, Tsukuba City, Ibaraki 305-8575, Japan
5 Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tennodai, Tsukuba City, Ibaraki 305-8575, Japan
6 Tsukuba Clinical Research and Development Organization, University of Tsukuba, Tennodai, Tsukuba City, Ibaraki 305-8575, Japan
7 Tokyo Metropolitan Neurological Hospital, Musashidai, Fuchu City, Tokyo 183-0042, Japan
8 Department of Pathology, Gunma University, Showa-cho, Maebashi City, Gunma 371-8511, Japan
9 Harajuku Rehabilitation Hospital, Jingumae, Shibuya-ku, Tokyo 150-0001, Japan
10 Division of Radiation Oncology, Nippon Medical School Hospital, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
11 Department of Neurosurgery, The Jikei University School of Medicine, Nishishinbashi, Minato-ku, Tokyo 105-8471, Japan
12 Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo City, Hokkaido 060-8638, Japan
13 Department of Neurosurgery, Tohoku University, Seiryo-machi, Aoba-ku, Sendai City, Miyagi 980-8575, Japan
14 Department of Neurosurgery, Yokohama City University, Kanazawa-ku, Yokohama City, Kanagawa 236-0004, Japan
15 Department of Neurosurgery, University of Yamanashi, Shimokawahigashi, Chuo City, Yamanashi 409-3898, Japan
16 Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54, Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8501, Japan
17 Department of Neurosurgery, Kobe University, Kusunoki-cho, Chuo-ku, Kobe City, Hyogo 650-0017, Japan
18 Department of Neurosurgery, Saga University, 1-1-1, Nabeshima, Saga City, Saga 849-8501, Japan
19 Department of Neurosurgery, Kurume University, 67, Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan
20 Department of Neurosurgery, 2-2-1, Kumamoto University, Honjo, Chuo-ku, Kumamoto 860-8556, Japan
21 Department of Neurosurgery, Dokkyo Medical University, 881, Kitakobayashi, Mibu, Shimotsugagun, Tochigi 321-0293, Japan
22 Department of Neurosurgery, Osaka Metropolitan University, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8585, Japan
23 Cell-Medicine Inc., Sengen, Tsukuba City, Ibaraki 305-0047, Japan
Clinical Trial Note
Abstract
This multi-institutional, double-blind, randomized, placebo-controlled phase III trial was designed to evaluate the efficacy and safety of Cellm-001, an autologous formalin-fixed brain tumor immunostimulant, for newly diagnosed glioblastoma with gross total resection to prolong overall survival (OS) and prevent recurrence after surgery. One hundred twelve patients are to be randomized 1:1 to either Cellm-001 with standard chemoradiotherapy (CRT) or saline solution with standard CRT. Randomization is based on the following stratified randomization criteria: age, Karnofsky Performance Status, and the presence or absence of photodynamic therapy (PDT). The primary endpoint is OS and secondary outcomes are progression-free survival (PFS), OS and PFS with and without radiographically residual lesions as subgroups, OS and PFS with and without PDT, p53-negative OS and PFS, high Cluster of Differentiation-8 score OS and PFS, OS associated with death in primary disease, and 24-month OS and PFS rates. All institutions received ethical committee approval and patient enrollment began in 2021.
Importance of the study:
Given the growing interest in immunotherapy (IMT), we developed an autologous formalin-fixed tumor vaccine (AFTV) manufactured from the patient’s own glioblastoma multiforme (GBM) tissue in paraffin-embedded blocks made from the resected tumor and a double-blind, randomized phase IIB trial of AFTV with temozolomide in newly diagnosed GBM was conducted. The 3-year progression-free survival (PFS) rate for patients with gross total resection (GTR) on imaging tended toward improvement: 81% in the AFTV group versus 46% in the placebo group (P = .067). Based on these IIB results, the feasibility of conducting a phase III trial was confirmed for IIB-eligible patients with total resection. We here plan to conduct the world’s first double-blind, randomized, placebo-controlled phase III trial using Cellm-001 to demonstrate autologous tumor immunostimulant efficacy. This IMT, in combination with sub-analyses (GTR, P53 status, CD8 score, and other factors) to be validated, is expected to be a breakthrough in effective standards of care for the treatment of GBM.
Trial registration:
Registry number: jRCT2031200153; Date of Registration: 20 /October, /2020; Date of First Patient Enrollment: 14 /January/, 2021.
