UMIN-CTR Clinical Trial

Basic information
Public title	Safety assessment of neoantigen peptides-loaded dendritic cell vaccination therapy.
Acronym	Vaccination with neoantigen-loaded DCs
Scientific Title	Safety assessment of neoantigen peptides-loaded dendritic cell vaccination therapy.
Scientific Title:Acronym	Vaccination with neoantigen-loaded DCs
Region	Japan

Condition
Condition	Malignant tumor (except leukemia)
Classification by specialty	Medicine in general Gastroenterology Hepato-biliary-pancreatic medicine Cardiology Pneumology Endocrinology and Metabolism Nephrology Neurology Surgery in general Gastrointestinal surgery Hepato-biliary-pancreatic surgery Chest surgery Endocrine surgery Breast surgery Obsterics and gynecology Pediatrics Ophthalmology Dermatology Oto-rhino-laryngology Urology Oral surgery Neurosurgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	Safety
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	Safety
Key secondary outcomes	Efficacy

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Vaccine
Interventions/Control_1	neoantigen peptides-loaded (autologous) dendritic cells
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	12 years-old <=
Age-upper limit	85 years-old >=
Gender	Male and Female
Key inclusion criteria	A patient must: - have ECOG Performance Status of 0, 1 and 2. - maintain adequate function of key organs when the eligibility is confirmed, in particular: 1. haemoglobin 8.0 g/dl or more 2. platelet 50.000 /mm3 or more 3. total bilirubin 3 x ULN or more 4. AST/ALT 3 x ULN or less 5. creatinine 3 x ULN or less - provide written consent for genetic analysis of tumor sample; neoantigen-screening analysis, and for treatment of those neoantigens-loaded DC vaccination. - have a proper mental condition and an ability to recognize the object and contents of the study when informed consent is obtained.
Key exclusion criteria	A patient must not: - be impossible to obtain blood sample by Leukapeheresis. - be positive in HIV antibody test. - have active auto-immune disorder. - have serious underlying disease. - be pregnant (including pregnancy seeker) - be judged ineligibles by clinician in this trial.
Target sample size	20

Research contact person
Name of lead principal investigator	1st name Keishi Middle name Last name Tanigawa
Organization	Bio-Thera Kai,Non-profit medicalcorporation
Division name	Bio-Thera Clinic
Zip code	1600022
Address	5-6-12 Shinjyuku, Sinjyukuku, Tokyo 1600055 Japan
TEL	03-5919-1762
Email	tanigawa@bio-c.jp

Public contact
Name of contact person	1st name Yasunobu Middle name Last name Kobayashi
Organization	Bio-Thera Kai,Non-profit medicalcorporation
Division name	Bio-Thera Clinic
Zip code	1600022
Address	5-6-12 Shinjyuku, Sinjyukuku, Tokyo 1600055 Japan
TEL	03-5919-1762
Homepage URL
Email	ykobayashi@bio-c.jp

Sponsor
Institute	Bio-Thera Clinic
Institute
Department

Funding Source
Organization	none
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Bio-Thera Clinic IRB
Address	5-6-12 Shinjyuku, Shinjyuku-ku, Tokyo 1600022 Japan
Tel	0359191761
Email	info@bio-c.jp

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

Other administrative information
Date of disclosure of the study information	2018 Year 11 Month 27 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	19
Results	Neoantigen DCs would be a safe treatment method. Neoantigen DCs would induce the acquisition of immune reaction against neoantigens.
Results date posted	2021 Year 12 Month 21 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Patients with solid carcinoma who implemented the inclusion criteria of this study were eligible for enrollment in this prospective study. After patients had received a full explanation according to the protocol, they were requested to provide informed consent to participate in this study. From August 06, 2018 to August 05, 2021, a total 20 patients were enrolled in this study. The patient characteristics was as follows: median age, 51.5 (range 32 - 68) years; sex (male: female) = 11: 9; primary lesion (brain, nasopharynx, breast, lung, stomach, jejunum, colon, rectum, liver, biliary duct, pancreas, uterine cervix, bladder, and soft tissue) = 2, 1, 2, 1, 1, 1, 2, 2, 1, 1, 3, 1, 1, and 1, respectively. Fifteen and 4 patients had undergone surgery and radiotherapy before this study, respectively. Chemotherapy was concurrently performed in 15 patients while they participated in this study.
Participant flow	The 20 patients were vaccinated weekly for 8 times with neoantigen pulsed dendritic cells (neoantigen DCs) plus ex-vivo activated T-cell transfer. The primary endpoint was to evaluate the safety of neoantigen DCs, which was determined with physical exams and blood tests. Blood tests were performed, before 1st, after 4th, and 8th administration of neoantigen DCs. The secondary endpoint was to evaluate the acquisition of immune reaction against neoantigens after intradermal administration of neoantigen DCs. It was determined by confirming redness and induration of the skin (Delayed-type hypersensitivity (DTH)) at injection site 48 hours from administration of neoantigen DCs. One of the 20 patients withdrew after 7th administration. Remaining 19 patients completed the original protocol.
Adverse events	Adverse events were observed in 11 patients as follows: adverse events (reduction of hemoglobin, reduction in hemoglobin number, increase in AST level, increase in total bilirubin level, appetite loss, and fatigue) = 8, 1, 2, 1, 3, and 5, respectively. JCOG-CTCAE (v5.0) grade was as follows: grade (1: 2: 3) = 4: 10: 6. All patients with adverse events underwent concurrent chemotherapy. We considered all adverse events were related to drug toxicity of chemotherapy. One of the 20 patients withdrew after 7th administration because of refractory liver abscess and severe pneumonia which were considered to be a postoperative complication and an adverse event derived from chemotherapy.
Outcome measures	Concerning the primary endpoint, no adverse events associated to neoantigen DCs were observed. Concerning the secondary endpoint, DTH was observed in 19 patients whereas it was negative in 1 case with cervical cancer. This patient had intractable pelvic abscess as an adverse after surgery and radiotherapy, and that would prevented DTH.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2018 Year 08 Month 06 Day
Date of IRB	2018 Year 05 Month 21 Day
Anticipated trial start date	2018 Year 10 Month 01 Day
Last follow-up date	2021 Year 09 Month 10 Day
Date of closure to data entry	2021 Year 09 Month 10 Day
Date trial data considered complete	2021 Year 09 Month 10 Day
Date analysis concluded	2021 Year 09 Month 10 Day

Other
Other related information	The costs associated with several treatments and examinations in this study shall be borne by each patient.

Management information
Registered date	2018 Year 11 Month 27 Day
Last modified on	2021 Year 12 Month 21 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000039932