UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase 1/2 clinical trial of immunotherapy with fusions of tumor cells and dendritic cells for pediatric refractory brain tumor
Title of the study (Brief title)	Dendritic cell-based immunotherapy for pediatric refractory brain tumor
Region	Japan

Condition
Condition	Pediatric refractory brain tumor
Classification by specialty	Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety and efficacy of immunotherapy with fusion cells of tumor cells and dendritic cells for refractory brain tumor in childhood and AYA.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I,II

Assessment
Primary outcomes	Safety
Key secondary outcomes	2-year overall survival (OS) rate, 1-year progression free survival (PFS) rate, iRANO criteria

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Vaccine
Interventions/Control_1	In Phase 1, we evaluate the safety (DLT) by three steps according to 3+3 design method. In Phase 2, we evaluate the safety and efficacy with 0.5-10 x10^6 cells in dendritic cell count. Fusion cell inoculation will be repeated 3-10 times in each 28-84 days cycle.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	3 years-old <=
Age-upper limit	25 years-old >
Gender	Male and Female
Key inclusion criteria	<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. WBC > 1,500/microL Platelet > 50,000/microL Hb > 9.0/dL Serum creatinine < 3-fold the upper limit of the normal range based on each age (ULN) Total bilirubin < 3-fold the ULN AST, ALT < 120U/L <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.
Key exclusion criteria	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. 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.
Target sample size	20

Research contact person
Name of lead principal investigator	Takaaki Yanagisawa
Organization	Jikei University School of Medicine
Division name	Neurosurgery
Address	3-25-8 Nishishinbashi Minato-ku, Tokyo
TEL	81-3-3433-1111
Email	takaakipno@jikei.ac.jp

Public contact
Name of contact person	Masayoshi Yamaoka
Organization	Jikei University School of Medicine
Division name	Pediatrics
Address	3-25-8 Nishishinbashi Minato-ku, Tokyo
TEL	81-3-3433-1111
Homepage URL
Email	yamaoka@jikei.ac.jp

Sponsor
Institute	Jikei University School of Medicine
Institute
Department

Funding Source
Organization	Jikei University School of Medicine
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	東京慈恵会医科大学附属病院

Other administrative information
Date of disclosure of the study information	2018 Year 02 Month 15 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2018 Year 02 Month 08 Day
Anticipated trial start date	2018 Year 02 Month 15 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2018 Year 02 Month 15 Day
Last modified on	2018 Year 02 Month 15 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035722