UMIN-CTR Clinical Trial

Public title

WT1-antigen specific TCR-gene transduced T lymphocytes transfer using MS3-WT1-siTCR vector for acute myelogeneous leukemia and myelodysplastic syndrome

Acronym

siTCR-WT1-AML/MDS gene therapy

Scientific Title

WT1-antigen specific TCR-gene transduced T lymphocytes transfer using MS3-WT1-siTCR vector for acute myelogeneous leukemia and myelodysplastic syndrome

Scientific Title:Acronym

siTCR-WT1-AML/MDS gene therapy

Region

Japan

Condition

acute myelogenous leukemia, myelodysplastic syndrome

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

Safety of WT1-TCR gene transduced cell transfer and WT1 peptide vaccine

Basic objectives2

Others

Basic objectives -Others

# Cell kinetics of TCR-gene transducsed cells in peripheral blood
# Hematological effect, including molecular levels using PCR methods
# Immunological analysis

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I

Primary outcomes

# Occurence of adverse events
# Changes of laboratory data
# RCR(replication competent retrovirus) excretion
# Clonal changes of TCR-gene transduced T lymphocytes

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Dose comparison

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

# WT1-TCR gene transduced lymphocyte transfer
two doses of 2x10*8 cells (day0, day28)
# WT1 peptide vaccination
two SQ injections of 300mcg each (day 30, day44)

Interventions/Control_2

# WT1-TCR gene transduced lymphocyte transfer
two doses of 1x10*9 cells (day0, day28)
# WT1 peptide vaccination
two SQ injections of 300mcg each (day 30, day44)

Interventions/Control_3

# WT1-TCR gene transduced lymphocyte transfer
two doses of 5x10*9 cells (day0, day28)
# WT1 peptide vaccination
two SQ injections of 300mcg each (day 30, day44)

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. Patient diagnosed as either of the followings;
a) acute myelogenous leukemia, relapsed or resistent to primary therapy, including atypical leukemia and transformed from myelodysplastic syndrome
b) therapy-resistent myelodysplastic syndrome, not indicated for hematopoietic stem cell transplant
2. HLA-A*24:02-positive
3. PCR-confirmed WT1-antigen expression on leukemic or MDS cells
4. Performance status(ECOG) 0 to 2
5. Aged 20 years or more
6. Full recovery after the previous therapy
7. Normal major organ function, and meeting the criteria below
# Serum total bilirubin within three times of upper normal level
# AST(GOT)/ALT(GPT) within three times of upper normal level
# Serum creatinine within three times of upper normal level
# left ventricular ejection fraction of 55% or more
# Arterial oxygen saturation of 94% or more
8. Having written informed consent

Key exclusion criteria

1.Having the 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
2. History of severe allergy
3. Either of HBV, HCV, HIV and HTLV-1 infection
4. Expected life splan of 4 months or less
5. Uncontrolled pleural effusion, ascites or pericardial effusion
6. CNS involvement affecting safety issues
7. Systemic corticostoroid (prednisolone of 0.5mg/kg/day or more), or immuno-suppressive therapy
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 months from the previous enrollment to clinical trials
11. Received allogeneic hematopoietic stem cell transplantation
12. Inappropriate for study entry judged by an attending physician

Target sample size

9

Name of lead principal investigator

1st name
Middle name
Last name	Hiroshi Shiku

Organization

Mie University Graduate School of Medicine

Division name

Department of Immuno-Gene Therapy

Zip code

Address

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

TEL

059-231-5187

Email

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

Name of contact person

1st name
Middle name
Last name	Shinichi Kageyama

Organization

Mie University Graduate School of Medicine

Division name

Department of Immuno-Gene Therapy

Zip code

Address

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

TEL

059-231-5187

Homepage URL

http://www.shikuken.jp/

Email

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

Institute

Mie University, Ehime University, Fujita Health University, Nagoya University, Takara Bio Inc.

Institute

Department

Personal name

Organization

Mie University,Ehime University, Fujita Health University, Nagoya University(MEXT, Japan), and Takara Bio Inc.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Ehime University, Fujita Health University, Nagoya University, Takara Bio Inc.

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

三重大学医学部附属病院（三重県）、愛媛大学医学部附属病院（愛媛県）、藤田保健衛生大学病院（愛知県）、名古屋大学医学部附属病院（愛知県）

Date of disclosure of the study information

2013

Year

08

Month

19

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://www.bloodjournal.org/content/130/18/1985.long?sso-checked=true

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

2012

Year

10

Month

01

Day

Date of IRB

Anticipated trial start date

2013

Year

08

Month

19

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

08

Month

19

Day

Last modified on

2018

Year

12

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012910