UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	WT1-antigen specific TCR-gene transduced T lymphocytes transfer using MS3-WT1-siTCR vector for acute myelogeneous leukemia and myelodysplastic syndrome
Title of the study (Brief title)	siTCR-WT1-AML/MDS gene therapy
Region	Japan

Condition
Condition	acute myelogenous leukemia, myelodysplastic syndrome
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Dose comparison
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Hiroshi Shiku
Organization	Mie University Graduate School of Medicine
Division name	Department of Immuno-Gene Therapy
Address	2-174, Edobashi, Tsu, Mie 514-8507, Japan
TEL	059-231-5187
Email	shiku@clin.medic.mie-u.ac.jp

Public contact
Name of contact person	Shinichi Kageyama
Organization	Mie University Graduate School of Medicine
Division name	Department of Immuno-Gene Therapy
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

Sponsor
Institute	Mie University, Ehime University, Fujita Health University, Nagoya University, Takara Bio Inc.
Institute
Department

Funding Source
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

Other related organizations
Co-sponsor	Ehime University, Fujita Health University, Nagoya University, Takara Bio Inc.
Name of secondary funｄer(s)

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）、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）

Other administrative information
Date of disclosure of the study information	2013 Year 08 Month 19 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 10 Month 01 Day
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

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://www.bloodjournal.org/content/130/18/1985.long?sso-checked=true
Results
Other related information

Management information
Registered date	2013 Year 08 Month 19 Day
Last modified on	2018 Year 12 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012910