UMIN-CTR Clinical Trial

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

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

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

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

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Nagasaki University Hospital

Institute

Department

Personal name

Organization

Tella Inc

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

08

Month

22

Day

URL releasing protocol

https://ar.iiarjournals.org/content/40/10/5687.long

Publication of results

Published

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

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 related information

Registered date

2013

Year

08

Month

22

Day

Last modified on

2021

Year

02

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013518