UMIN-CTR Clinical Trial

Basic information
Public title	Phase I/IIa clinical study of the immunotherapy using ZNK cell for solid cancer
Acronym	Phase I/IIa clinical study of the immunotherapy using ZNK cell for solid cancer
Scientific Title	Phase I/IIa clinical study of the immunotherapy using ZNK cell for solid cancer
Scientific Title:Acronym	Phase I/IIa clinical study of the immunotherapy using ZNK cell for solid cancer
Region	Japan

Condition
Condition	Solid cancer, Malignant tumor
Classification by specialty	Gastroenterology Hepato-biliary-pancreatic medicine Pneumology Gastrointestinal surgery Hepato-biliary-pancreatic surgery Chest surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The primary objective of this study is to assess the safety and feasibility of the newly developed immunotherapy using ZNK cell for solid cancer patients. The secondary objectives are to confirm the maximum tolerance dose of ZNK cells and to assess the anti-tumor immune response as an efficacy of this regimen on RECIST guideline.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I,II

Assessment
Primary outcomes	Adverse events and safety Maximum tolerated dose (MTD) Ratio of NK cell in the blood after the ZNK cell dosage
Key secondary outcomes	-Antitumor immune response (RECIST) -Progress- free survival(PFS) *four weeks after the last ZNK cell injection and every three months until progressive disease (PD) is diagnosed. -Overall survival(OS) *follow-up phase: for 2 years

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	ZNK cell is injected approximately every two weeks for a total six times per case. The dosage amount of ZNK cells are 10^6 cells on the first injection, 10^7 cells on the second and 10^8 cells on the third to sixth injections. Injections of ZNK cell can be repeated unless patient's general condition is aggravated or adverse event, which cause incapability of continuing to administrate ZNK cell, is observed.
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	20 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	The subjects must satisfy the following conditions. 1) Patients must be histopathologically or cytologically diagnosed as solid cancer. 2) Patients must have target lesions for evaluating the efficacy by RECIST. 3) Patients must be at a score level of 0 or 1 of performance status (ECOG). 4) Patient's age must be between 20 to 75 years old. 5) Concerning the function of major organs (bone marrow, liver, kidney, and etc.), patients must satisfy the followings: a) WBC >=3,000/mm3 b) Neutrophil >=1,500/mm3 c) Platelet >=80,000/mm3 d) Hemoglobin >=9.0g/dL e) AST, ALT<=2.5 times of facility criterion f) Total bilirubin<=2.5 times of facility criterion g) Serum Creatinine <=1.5mg/dL h) No serious abnormality on an electrocardiogram 6) Patients must be expected to survive more than four months from initial administration of ZNK cell. 7) Written informed consent must be obtained from patients.
Key exclusion criteria	The following patients must be excluded: 1) Patients with hematological neoplasms including leukemia. 2) Patients with possibility of severe bleeding coursed by anti-tumor effects such as metastatic brain tumor or central type of lung cancer. 3) Patients with active synchronous malignancies. 4) Patients with history of a serious allergic reaction. 5) Patients with serious complications or coexisting illness such as myelosuppression, infectious disease, interstitial pneumonitis, pulmonary fibrosis, or poorly controlled cardiac, renal, liver and diabetes. 6) Patient with pleural or pericardial effusion with requiring treatment. 7) Woman who are pregnant or breastfeeding, or with the will of the pregnancy. 8) Man with the will to impregnate 9) Patients with carrier of HTLV-1, HIV, HBV, HCV, and syphilis spirochete. 10) Patients with severe mental disorder. 11) Patient with history of the autoimmune disease. 12) Patients who are taking immunosuppressant. 13) Patients who are judged to be inadequate to participate in this study by doctors responsible for this study.
Target sample size	10

Research contact person
Name of lead principal investigator	1st name Middle name Last name Kazuhiro Nagai
Organization	Nagasaki University Hospital
Division name	Transfusion and Cell Therapy Unit
Zip code
Address	Sakamoto 1-7-1, Nagasaki, Japan
TEL	095-819-7493
Email	agwkn@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Kazuhiro Nagai
Organization	Nagasaki University Hospital
Division name	Transfusion and Cell Therapy Unit
Zip code
Address	Sakamoto 1-7-1, Nagasaki, Japan
TEL	095-819-7493
Homepage URL
Email	agwkn@nagasaki-u.ac.jp

Sponsor
Institute	Nagasaki University Hospital
Institute
Department

Funding Source
Organization	Tella Inc
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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	2013 Year 08 Month 22 Day

Related information
URL releasing protocol	https://ar.iiarjournals.org/content/40/10/5687.long
Publication of results	Published

Result
URL related to results and publications	https://ar.iiarjournals.org/content/40/10/5687.long
Number of participants that the trial has enrolled	9
Results	A total of nine patients were enrolled in this study, with one recruited twice. Overall, neither grade 2 or higher toxicities (CTCAE v5.0) caused by cell administration, nor adverse events causing discontinuation of protocol treatment were found. The maximally tolerated dose was therefore considered to be at least 10^8 cells. The overall response rate was 40.0% in 10 net cases.
Results date posted	2021 Year 02 Month 15 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	The diagnoses of patients were as follows: Four patients with colonic cancer, two patients with adenocystic carcinoma, and one patient each with renal, pancreatic, and ovarian cancer.
Participant flow	A total of 9 patients were enrolled in the current study in accordance to the inclusion criteria of this study.
Adverse events	The most common any grade AEs were grade 1 fatigue (n=5, 50.0%) and anorexia (n=4, 40.0%). These AEs were considered to be mainly due to exacerbation of the underlying disease.In case 2, grade 1 fever was observed for a few days from several hours after administration, and symptomatic treatment was temporarily required but the symptoms resolved. In case 4, a grade 1 skin rash appeared locally 6 to 7 hours after the administration and was observed over several days, then disappeared spontaneously without the need for treatment. There were no cases with hematological AEs. Overall, no grade 2 or higher CTCAE v5.0 toxicities associated with ZNK cell administration were found, and none of the patients reported an AE that led to discontinuation of ZNK cell treatment.
Outcome measures	These results demonstrate that autologous ZNK cells are safe and well-tolerated in patients with different types of advanced solid tumors.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 04 Month 23 Day
Date of IRB	2013 Year 07 Month 21 Day
Anticipated trial start date	2013 Year 08 Month 22 Day
Last follow-up date	2019 Year 07 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2013 Year 08 Month 22 Day
Last modified on	2021 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=R000013518