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Dendritic cell-based immunotherapy for pediatric refractory brain tumor

Dendritic cell-based immunotherapy for pediatric refractory brain tumor

Kojima Hiromi

Nov. 30, 2022

4

Age :7 to 12 years old 4 cases Complications: None Number of doses: 3 doses in 2 cases, 5 doses in 1 case, 7 doses in 1 case

Obtained consent in 6cases Number of registered cases: 6cases (4 completed, 2 discontinued; discontinued due to increase in disease before cellular injection) February 08, 2018:Start of research May 07, 2018: Start of registration (1st case registration date) November 30, 2022: Study discontinued

Disease occurred in 1 of 4 patients (25%). Age: 8 years; event name: fever; treatment: none; outcome: recovery; relevance: undeniable."

Primary evaluation (safety): In all 4 patients treated, only 1 of 4 (25%) developed fever. Secondary efficacy endpoints: 2-year overall survival (50%), 1-year progression-free survival (50%)

Safety: All 4 patients treated were safe. Efficacy: All four patients showed some response to treatment: two survived without recurrence, one had a recurrence but changed to a very localized pattern of recurrence, and one had a disseminated recurrence that resolved with the treatment. Another patient had a disseminated recurrence, but the primary tumor disappeared after treatment. However, the study was terminated due to implementation problems.

Mar. 10, 2023

No

https://jrct.mhlw.go.jp/latest-detail/jRCTc030190174

Yanagisaw Takaaki

The Jikei University Hospital

3-19-18 Nishishinbashi,Minato-ku,Tokyo-to

takaakipno@jikei.ac.jp

Akasaki Yasuharu

The Jikei University Hospital

3-19-18 Nishishinbashi,Minato-ku,Tokyo-to

+81-3-3433-1111

akasaki@jikei.ac.jp

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

<Tentative inclusion criteria>
Patients will be tentatively enrolled in this clinical trial, when they satisfy the following tentative inclusion criteria.
1) A patient who is suspected a relapse or refractory pediatric brain tumor with poor prognosis. 2) A patient who needs to receive a surgical tumor resection. 3) A patient who is tolerable to receive gathering peripheral blood mononuclear cells by an apheresis method. 4) Age at enrollment is 3 to <25 year-old 5) A patient who has grade 0 to 3 of the Performance Status. Patients with a PS score of 4 due to neurological symptoms associated with the primary disease may be eligible if patients could go to outpatient clinic without any respiratory supports. 6) A patient who is suspected to be alive for more than 3 months. 7) A patient who does not have multiple primary cancer. 8) A patient for whom either the legally acceptable representative or the patient (if aged > 16 years) have provided written voluntary consent to participation in this study after fully receiving and understanding the information about this study.
9) A patient who satisfies following criteria without functional failure of major organs, such as heart, lung, liver, kidney, and bone marrow etc.
<Final inclusion criteria>
Tentatively enrolled patients will be truly enrolled as a subject of this clinical trial, when they satisfy the following final inclusion criteria.
1) A patient who is histologically proven recurrent or refractory brain tumor.
2) A patient who has autologous cultured tumor cells available to fuse with dendritic cells.

1) A patient who has sever immune deficiency. 2) A patient who has a past or current history of autoimmune disease. 3) A patient who is administrated immunosuppressive agents for a long period, and is difficult to stop it. 4) A patient who received chemotherapy (including with molecular target therapy) or radiotherapy within 21 days. 5) A patients who underwent allogeneic hematopoietic stem cell transplant. 6) A patient who had recovered from some viral infection (influenza virus or gastroenteritis) within 14 days. 7) A patient who has an allergy to biological medicines. 8) A patient who previously received WT1 peptide vaccine or other immunotherapy (except our dendritic cell vaccine). 9) A patient who has positive of HBs antigen, HIV antibody, HCV antibody, or HTLV antibody. 10) A patient who has severe infectious disease over Grade 3 of CTCAE v4.0. 11) A patient who has sever lung disease (Class 3 or more in the Hugh-Jones classification). 12) A patient who has severe heart disease (Class 3 or more in the NYHA). 13) A patient who has some uncontrollable complication. 14) A pregnant or lactating patient. 15) A patient who is involved in other clinical trials. 16) A patients who are inappropriate for participation in the study for other reasons in the opinion of the investigator or sub-investigator.

Both

Pediatric brain tumor

1) Mature dendritic cells (DCs) are generated from PBMCs by an apheresis collection method, and cultured in AIM-1 medum with GM-CSF, IL-4, TNF-alfa.
2) Generation of primary cultured glioma cells from surgical specimens.
3) DCs were mixed with lethally irradiated (300 Gy) primary cultured tumor cells. The ratio of DCs and tumor cells ranged from 2:1 to 10:1 depending on the numbers of acquired DCs and glioma cells. Fusion was started by adding polyethylene glycol. FCs were cultured in AIM-5 medium with Poly I:C/IL-10-siRNA, GM-CSF, IL-4 and TNF-alfa for 24 h. FCs suspended in 0.5 mL normal saline were inoculated intradermally in the cervical region.In Phase 1, we evaluate the safety (DLT) by two steps. In Phase 2, we evaluate the safety and efficacy with 0.5-5 x1,000,000 cells in dendritic cell count. Fusion cell inoculation will be repeated 3-10 times in each 28-84 days cycle.

Safety (ratio and severity of adverse events)

2-year overall survival (OS) rate, 1-year progression free survival (PFS) rate, iRANO criteria

Complete

+81-3-3433-1111

Mar. 09, 2022