Phase I/IIa trial of chemoradiotherapy plus autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma: Association between complete resection and delayed-type hypersensitivity response.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e13029-e13029 ◽  
Author(s):  
Eiichi Ishikawa ◽  
Yoshihiro Muragaki ◽  
Tetsuya Yamamoto ◽  
Takashi Maruyama ◽  
Koji Tsuboi ◽  
...  
Keyword(s):  
Phase I ◽  
Tumor Vaccine ◽  
Complete Resection ◽  
Delayed Type Hypersensitivity ◽  
Hypersensitivity Response ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Delayed Type Hypersensitivity Response ◽  
Formalin Fixed ◽  
Fixed Tumor

Phase I/IIa trial of autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 2069-2069
Author(s):  
Y. Muragaki ◽  
T. Maruyama ◽  
H. Iseki ◽  
K. Tsuboi ◽  
A. Matsumura ◽  
...  
Keyword(s):  
Phase I ◽  
Tumor Vaccine ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Formalin Fixed ◽  
Fixed Tumor

Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

2014 ◽  
Vol 121 (3) ◽  
pp. 543-553 ◽  
Author(s):  
Eiichi Ishikawa ◽  
Yoshihiro Muragaki ◽  
Tetsuya Yamamoto ◽  
Takashi Maruyama ◽  
Koji Tsuboi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Treatment Regimen ◽  
Tumor Vaccine ◽  
Delayed Type Hypersensitivity ◽  
Karnofsky Performance Scale ◽  
Newly Diagnosed ◽  
Fractionated Radiotherapy ◽  
Formalin Fixed ◽  
Fixed Tumor

Object Temozolomide (TMZ) may enhance antitumor immunity in patients with glioblastoma multiforme (GBM). In this paper the authors report on a prospective Phase I/IIa clinical trial of fractionated radiotherapy (FRT) concomitant with TMZ therapy, followed by treatment with autologous formalin-fixed tumor vaccine (AFTV) and TMZ maintenance in patients with newly diagnosed GBM. Methods Twenty-four patients (age 16–75 years, Karnofsky Performance Scale score ≥ 60% before initiation of FRT) with newly diagnosed GBM received a total dose of 60 Gy of FRT with daily concurrent TMZ. After a 4-week interval, the patients received 3 AFTV injections and the first course of TMZ maintenance chemotherapy for 5 days, followed by multiple courses of TMZ for 5 days in each 28-day cycle. Results This treatment regimen was well tolerated by all patients. The percentage of patients with progression-free survival (PFS) ≥ 24 months was 33%. The median PFS, median overall survival (OS), and the actuarial 2- and 3-year survival rates of the 24 patients were 8.2 months, 22.2 months, 47%, and 38%, respectively. The median PFS in patients with a delayed-type hypersensitivity (DTH) response after the third AFTV injection (DTH-2) of 10 mm or larger surpassed the median length of follow-up for progression-free patients (29.5 months), which was significantly greater than the median PFS in patients with a smaller DTH-2 response. Conclusions The treatment regimen was well tolerated and resulted in favorable PFS and OS for newly diagnosed GBM patients. Clinical trial registration no.: UMIN000001426 (UMIN clinical trials registry, Japan).

scholarly journals OS09.8 Randomized placebo-controlled trial of autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii20-iii20 ◽  
Author(s):  
Y. Muragaki ◽  
T. Maruyama ◽  
E. Ishikawa ◽  
M. Nitta ◽  
S. Ikuta ◽  
...  
Keyword(s):  
Tumor Vaccine ◽  
Controlled Trial ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Formalin Fixed ◽  
Fixed Tumor

Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma

2011 ◽  
Vol 115 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Yoshihiro Muragaki ◽  
Takashi Maruyama ◽  
Hiroshi Iseki ◽  
Masahiko Tanaka ◽  
Chie Shinohara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Vaccine ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Fractionated Radiotherapy ◽  
Newly Diagnosed Glioblastoma ◽  
Analysis Of Results ◽  
Formalin Fixed ◽  
Fixed Tumor

Object The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme. Methods Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done—one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment. Results The median duration of overall survival was 19.8 months (95% CI 13.8–31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3–13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection. Conclusions The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

scholarly journals IMPS-23RETROSPECTIVE ANALYSIS CLINICAL RESULTS OF AUTOLOGOUS FORMALIN-FIXED TUMOR VACCINE FOR NEWLY DIAGNOSED GLIOBLASTOMA

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v118.2-v118
Author(s):  
Takashi Maruyama ◽  
Yoshihiro Muragaki ◽  
Masayuki Nitta ◽  
Hiroshi Iseki ◽  
Tadao Ohno ◽  
...  
Keyword(s):  
Tumor Vaccine ◽  
Clinical Results ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Formalin Fixed ◽  
Fixed Tumor

A clinical trial of autologous formalin-fixed tumor vaccine (AFTV) for patients with glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2085-2085 ◽  
Author(s):  
K. Tsuboi ◽  
E. Ishikawa ◽  
T. Yamamoto ◽  
S. Takano ◽  
A. Matsumura ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mhc Class I ◽  
Tumor Tissue ◽  
Tumor Vaccine ◽  
Clinical Investigation ◽  
Class I ◽  
Delayed Type Hypersensitivity ◽  
Low Grade ◽  
Formalin Fixed ◽  
Fixed Tumor

2085 Background: This clinical pilot study is to investigate the safety, feasibility, plus clinical response of autologous formalin- fixed tumor vaccine (ATFV) in primary glioblastoma multiforme (GBM) patients. Methods: Eleven (8 recurrent and 3 initially treated) primary GBM patients were evaluated. AFTV was prepared from formalin-fixed tumor tissue or paraffin-embedded tissue and premixed with original adjuvant materials. A delayed-type hypersensitivity test (DTH) was performed before and after each course of ATFV treatment that comprised 3 vaccinations at a 5-site intradermal inoculation. In addition, immunohistochemical analysis of MIB-1, p53, and MHC class-I complex was performed on the tumor tissue to analyze the difference in the response to the treatment. Results: The treatment was well tolerated with only local induration and low-grade fever. Among the 11 patients, the best responses were 1 complete remission, 2 partial response, 1 no change, and 7 progressive disease. In this series, the median survival period was 7 months from the initiation of the AFTV treatment, and 3 of the 4 responders survived for more than 20 months after AFTV inoculation. DTH reactions, immunohistological analysis of p53 and MHC class-I complex, and patient status may be useful to predict the efficacy of this therapy. Conclusion: This study demonstrated that AFTV treatment is safe, feasible, and potentially beneficial. Further clinical investigation is highly desirable in order to improve the outcome of GBM patients. No significant financial relationships to disclose.

scholarly journals IMT-05 PHASE III RANDOMIZED CLINICAL TRIAL OF AFTV FOR NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii17-ii18
Author(s):  
Masayuki Nitta ◽  
Yoshihiro Muragaki ◽  
Eiichi Ishikawa ◽  
Takashi Maruyama ◽  
Soko Ikuta ◽  
...  
Keyword(s):  
Placebo Group ◽  
Local Treatment ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Total Removal ◽  
Double Blind ◽  
Significant Difference ◽  
Newly Diagnosed Glioblastoma ◽  
Formalin Fixed ◽  
Fixed Tumor

Abstract BACKGROUND The highly fatal glioblastoma has an extremely poor prognosis and development of a new treatment is desired. Local treatment is limited due to its high invasiveness, and immunotherapy utilizing self-immune mechanism is theoretically expected. An autologous formalin-fixed tumor vaccine (AFTV) is a vaccine that is prepared using formalin-fixed tumor tissue and recognizes tumor antigen peptides to induce cytotoxic T cells. We have previously conducted three clinical trials using AFTV for patients with newly diagnosed glioblastoma since 2004. The third trial was a double-blind multicenter phase IIb/III trial with 63 case registries, which did not make a significant difference in OS (study group 25 months, placebo group 31 months), the total removal group showed excellent clinical results (3-year survival rate; 65%, median survival; not reached). Since the study was designed to go to Phase III if the test group was not inferior to the placebo group, so it went on to go to Phase III. METHODS Target patients will be 80 patients with newly diagnosed glioblastoma undergoing pathologic diagnosis, who have undergone total removal of contrast-enhanced lesions and receive standard chemoradiation therapy. STUDY DESIGN Double-blind, 3-year enrollment period, 18-month observation period. Stratification factor: Photodynamic therapy (PDT), facility, age, KPS. Administration method: After standard chemoradiotherapy, in parallel with maintenance chemotherapy, a total of 9 times intradermal administration of vaccine. Primary endpoint: PFS of FAS patients, Secondary endpoints: 18 months PFS of the FAS patient, OS, PFS of the ITT analysis target case. Based on the results of the IIb trial, we limited the registered patients with total tumor removal, and in view of the fact that the prognosis of patients with combined PDT and AFTV were excellent, PDT was added to the stratification factor. We outline our efforts and problems aimed at clinical approval of AFTV for glioblastoma.

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