UMIN-CTR Clinical Trial

Public title

A phase I clinical study of immune cell therapy with MAGE-A4- or Survivin-specific Th1 cells for patients with refractory virulent tumors

Acronym

MAGE-A4/Survivin-specific Th1 cell therapy for cancer patients

Scientific Title

A phase I clinical study of immune cell therapy with MAGE-A4- or Survivin-specific Th1 cells for patients with refractory virulent tumors

Scientific Title:Acronym

MAGE-A4/Survivin-specific Th1 cell therapy for cancer patients

Region

Japan

Condition

Refractory cancer patients (MAGE-A4- or Survivin-expressing, non origin-limited) or the patients who refuse standard cancer therapy

Classification by specialty

Gastroenterology	Hepato-biliary-pancreatic medicine	Pneumology
Nephrology	Gastrointestinal surgery	Hepato-biliary-pancreatic surgery
Chest surgery	Breast surgery	Obstetrics and Gynecology
Oto-rhino-laryngology	Urology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To evaluate adverse events after repeated transfer of MAGE-A4- or Survivin-specific Th1 cells for patients with advanced cancers expressing MAGE-A4 or Survivin antigen

Basic objectives2

Others

Basic objectives -Others

To evaluate MAGE-A4 or Survivin specific immune responses and tumor responses after transfer of MAGE-A4- or Survivin-specific Th1 cells

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I

Primary outcomes

Safety: Dose limiting toxicity (DLT) and Type, frequency, and degree of adverse events (AE)

Key secondary outcomes

Efficacy: MAGE-A4 or Survivin-antigen specific immune responses (antibody production, CD4+T and CD8+T cell responses) and antitumor action

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Vaccine

Interventions/Control_1

Subcutaneous or peritumoral injection of MAGE-A4- or Survivin-specific Th1 cells (3x10^7cells), mixed with MAGE-A4- or Survivin-hepler pepitde (0.1 mg), at every two weeks, repeated 4 times

Interventions/Control_2

Subcutaneous or peritumoral injection of MAGE-A4- or Survivin-specific Th1 cells (10x10^7cells), mixed with MAGE-A4- or Survivin-hepler pepitde (0.1 mg), at every two weeks, repeated 4 times

Interventions/Control_3

Subcutaneous or peritumoral injection of MAGE-A4- or Survivin-specific Th1 cells (30x10^7cells), mixed with MAGE-A4- or Survivin-hepler pepitde (0.1 mg), at every two weeks, repeated 4 times

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

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Aged twenty or more at the time of informed consent
2) Patients with histologically-confirmed malignant neoplasm
3) Therapy-resistant cancer including chemotherapy and radio therapy, with clinical stage III or IV, recurrent cancer or patients who refuse the standard therapy
4) Patients with histologically-confirmed carcinoma. Therapy-resistant cancer including chemotherapy and radio therapy, with clinical stage III or IV, recurrent cancer, or advanced cancer patients who refuse the standard therapy
5) Performance status (ECOG) 0 to 2
6) At least four-month life expectancy
7) Normal bone-marrow and kidney function, meeting the criteria below;
Neutrophil cells>1500/microL
Lymphocytes>500/microL
Platelets>100000/microL
Hemoglobin>8.0 g/dL
Serum bilirubin<2 mg/dL
Serum creatinine<2.0 mg/dL (<2.5 mg/dL in Kidney cancer)
8) PCR/ IHC-confirmed MAGA-A4 or Survivin expressing tumor cells
9) Positive for HLA-DPB1*0501, HLA-DRB1*1403, HLA-DRB1*1501, HLA-DRB1*1502, or HLA-DRB1*0101 in MAGE-A4-specific Th1 cell therapy.
Positive for HLA-DRB1*0101, HLA-DR53, HLA-DQB1*0601, or HLA-DPB1*0501 in Survivin-specific Th1 cell therapy
10) Patients having written informed consent by their free will after explanation of the present study

Key exclusion criteria

1) Patients with the previous enrollment to clinical trials of cancer immune therapy for MAGE-A4 in MAGE-A4-specific Th1 cell therapy.
2) Patients with the previous enrollment to clinical trials of cancer immune therapy for Survivin in Survivin-specific Th1 cell therapy.
3) Pregnant women or women refused anticonception during the study
4) Men refused anticonception during the study
5) Lactating women or women refused lactating during the study
6) Severe bleeding disorders, meeting the criteria below;
PT<50%
APTT>60sec
Fbg<100mg/dl
FDP>20mg/ml
Severe bleeding case judged by an attending physician at the diagnosis
7) Active infection (HIV, HBV or HCV etc.)
8) Severe heart disease (NYHA class 3 or 4)
9) Autoimmune disease (scleroderma, Sjogren's syndrome, idiopathic thrombocytopenic purpura, multiple sclerosis, rheumatoid arthritis etc.)
10) Systemic administration of corticosteroid or immunosuppresive drugs during the study (Except local administration, inhaled drugs, and antiphlogistic analgetics).
11) Patient with impaired mental status in the study.
12) Inappropriate for study entry judged by an attending physician

Target sample size

18

Name of lead principal investigator

1st name
Middle name
Last name	Todo Satoru

Organization

Hokkaido University Graduated School of Medicine

Division name

Department of General Surgery

Zip code

Address

Kita-15, Nishi-7, Kita-ku, Sapporo

TEL

Email

Name of contact person

1st name
Middle name
Last name	Kitamura Hidemitsu

Organization

Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University

Division name

Bureau of MAGE-A4/Survivin Th1 cell therapy clinical study

Zip code

Address

Kita-15, Nishi-7, Kita-ku, Sapporo

TEL

011-706-9074

Homepage URL

Email

Institute

Department of General Surgery, Hokkaido University Graduated School of Medicine

Institute

Department

Personal name

Organization

NEDO (New Energy and Industrial Technology Development Organization), etc

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

1) Division of Immunoregulation, Institute for Genetic Medicine, Hokkaido University
2) Bioimmulance Co. Ltd

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

北海道大学病院/Hokkaido University Hospital

Date of disclosure of the study information

2011

Year

01

Month

07

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2010

Year

11

Month

11

Day

Date of IRB

Anticipated trial start date

2010

Year

12

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2011

Year

01

Month

06

Day

Last modified on

2013

Year

10

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005747