UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000002395
Receipt number R000002761
Scientific Title Adoptive transfer of lymphocytes transduced with MAGE-A4-specific TCR gene for therapy-resistant esophageal cancer
Date of disclosure of the study information 2009/08/28
Last modified on 2015/05/20 15:09:17

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Basic information

Public title

Adoptive transfer of lymphocytes transduced with MAGE-A4-specific TCR gene for therapy-resistant esophageal cancer

Acronym

Adoptive transfer of lymphocytes transduced with MAGE-A4-specific TCR gene

Scientific Title

Adoptive transfer of lymphocytes transduced with MAGE-A4-specific TCR gene for therapy-resistant esophageal cancer

Scientific Title:Acronym

Adoptive transfer of lymphocytes transduced with MAGE-A4-specific TCR gene

Region

Japan


Condition

Condition

Therapy-resistant esophageal cancer

Classification by specialty

Gastroenterology Hematology and clinical oncology Gastrointestinal surgery

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

To evaluate safety, kinetics and clinical responses after trasnfer of autologous lymphocytes tranduced with TCR-alpha/beta gene recognizing MAGE-A4-peptide

Basic objectives2

Pharmacokinetics

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I


Assessment

Primary outcomes

# Safety; adverse events, including laboratory data and replication competent retrovirus(RCR)/linear amplification mediated-PCR(LAM-PCR)

Key secondary outcomes

# Kinetics and tumor infiltration of TCR/gene-transduced lymphocytes
# Tumor-specific immune responses
# Tumor shrinkage


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine Gene

Interventions/Control_1

First cohort; three patinets
1.TCR-gene-transduced autologous lymphocytes infusion
2x10*8 cells, single dose, IV
2. MAGE-A4 peptide administration
300 micrograms, mixed with Montanide(incomplete Freund's adjuvant), SQ, on day 14 and 28 after lymphocytes infusion

Interventions/Control_2

Second cohort; three patinets
1.TCR-gene-transduced autologous lymphocytes infusion
1x10*9 cells, single dose, IV
2. MAGE-A4 peptide administration
300 micrograms, mixed with Montanide(incomplete Freund's adjuvant), SQ, on day 14 and 28 after lymphocytes infusion

Interventions/Control_3

Third cohort; three patinets
1.TCR-gene-transduced autologous lymphocytes infusion
5x10*9 cells, single dose, IV
2. MAGE-A4 peptide administration
300 micrograms, mixed with Montanide(incomplete Freund's adjuvant), SQ, on day 14 and 28 after lymphocytes infusion

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

1.Histologically-confirmed malignant esophageal tumor
2.Therapy-resistant cancer, including chemotherapy and radiotherapy, with clinical stage III or IV, recurrent, and metastatic disease
3.HLA-A2402-positive
4.PCR or immunohistochemistry-confirmed MAGE-A4-antigen expression of tumor cells
5.Having measurable tumor for assessing clinical responses
6.Performance status(ECOG) 0 to 1]
7.Aged 20 to 75 years
8.Recovery lasting after the previous therapy, including surgery, chemotherapy and radiotherapy
9.At least four-month life expectancy
10.Normal major organ function, and meeting the criteria below
# White cell counts 3,000/uL or more
# Neutrophils 1,500/uL or more
# Hemoglobin 8.0 g/dL or more
# Platelets 100,000/uL or more.
# Serum total bilirubin 2.0mg/dL or less
# AST(GOT)/ALT(GPT) 150IU/dL or less
# Serum creatinine 2.0mg/dL or less
# Aterial oxygen pressure 70 torr or more, or oxygen saturation 94% or more
11.Positive for HLA class I molecule on tumor cells
12.Having written informed consent

Key exclusion criteria

1.Having following serious complications
# Uncontrolled anigina pectoris, myocardial infarction, or heart failure
# Uncontrolled diabetes mellitus or hytertention
# Uncontrolled infection
# X-ray-proven interstitial pneumonia or pulmonary fibrosis
# Autoimmune disease
# Bleeding tendency; PT less than 50%, APTT more than 60sec, serum fibrinogen less than 100mg/dL, FDP more than 20ug/mL
Thrombosis tendency
2.History of serious hypersensitivity
3.Positive for HBs Ag, HCV Ab, HIV Ab, or HTLV-I Ab
4. Unctrolled pleural effusion, ascites, or pericardial effusion
5.Uncontrolled CNS metastasis
6.Systemic corticostoroid or immuno-suppressive therapy
7. Inappropriate for MAGE-A4 143-151 peptide administration, i.e. allergic to the peptide or adjuvant
8.Mental illness or drug dependency affecting informed consent
9.Pregnant, lactating, or possiblly pregnant women, or willing to be pregnant, or willing male partner, except having cryopreseved sperm
10. Lasting less than four weeks from the previous enrollment to clinical trials
11.Inappropriate for study entry judged by an attending physician.

Target sample size

9


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Hiroshi Shiku

Organization

Mie University Graduate School of Medicine

Division name

Immuno-Gene Therapy

Zip code


Address

2-174, Ebobashi, Tsu, Mie, 514-8507 Japan

TEL

059-231-5187

Email

shiku@clin.medic.mie-u.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Shinichi Kageyama

Organization

Mie University Graduate School of Medicine

Division name

Immuno-Gene Therapy

Zip code


Address

81-59-231-5187

TEL

059-231-5187

Homepage URL


Email

kageyama@clin.medic.mie-u.ac.jp


Sponsor or person

Institute

Mie University Hospital

Institute

Department

Personal name



Funding Source

Organization

Mie University

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor

Takara Bio Incorporation

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

三重大学医学部附属病院(三重県)


Other administrative information

Date of disclosure of the study information

2009 Year 08 Month 28 Day


Related information

URL releasing protocol


Publication of results

Published


Result

URL related to results and publications

http://clincancerres.aacrjournals.org/content/21/10/2268.full

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



Progress

Recruitment status

Completed

Date of protocol fixation

2009 Year 08 Month 19 Day

Date of IRB


Anticipated trial start date

2009 Year 08 Month 01 Day

Last follow-up date

2013 Year 04 Month 30 Day

Date of closure to data entry

2014 Year 02 Month 10 Day

Date trial data considered complete

2014 Year 02 Month 10 Day

Date analysis concluded

2014 Year 02 Month 10 Day


Other

Other related information



Management information

Registered date

2009 Year 08 Month 28 Day

Last modified on

2015 Year 05 Month 20 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002761


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name