UMIN-CTR Clinical Trial

Basic information
Public title	Investigator-initiated multi-institutional phase I clinical trial of NY-ESO-1-specific TCR gene-modified T cell therapy for adult T cell leukemia/lymphoma patients relapsed after allogeneic hematopoietic stem cell transplantation
Acronym	A phase 1 investigator-initiated study of TBI-1301-A for refractory ATLL experiencing recurrence after allo-HSCT
Scientific Title	Investigator-initiated multi-institutional phase I clinical trial of NY-ESO-1-specific TCR gene-modified T cell therapy for adult T cell leukemia/lymphoma patients relapsed after allogeneic hematopoietic stem cell transplantation
Scientific Title:Acronym	A phase 1 investigator-initiated study of TBI-1301-A for refractory ATLL experiencing recurrence after allo-HSCT
Region	Japan

Condition
Condition	Refractory ATLL experiencing recurrence after allogenic hematopoietic stem cell transplantation
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	NY-ESO-1-specific TCR gene transduced donor-derived T lymphocytes (TBI-1301-A) are transfused to HLA-A*02:01 or HLA-A*02:06 positive and NY-ESO-1 expressing patients with refractory ATLL experiencing recurrence after allogenic hematopoietic stem cell transplantation. The objective is to evaluate the safety, pharmacokinetics of TBI-1301-A, clinical effects, and GVHD severity in this gene therapy.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Safety - Frequency of occurring adverse event - Frequency of occurring product failure - Appearance of replication competent retrovirus (RCR) - Appearance of clonality
Key secondary outcomes	1) Pharmacokinetics of blood TBI-1301-A 2) Clinical effects 3) Transition of laboratory test values 4) Appearance and severity of GVHD

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine Gene
Interventions/Control_1	TBI-1301-A is transfused once after pretreatment by cyclophosphamide
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

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients: 1) Patient with refractory ATLL experiencing recurrence after allogenic hematopoietic stem cell transplantation from his/her relative or from an unrelated individual registrated in Japan Marrow Donor Program (JMDP) 2) HLA-A*02:01 or HLA-A*02:06 positive 3) NY-ESO-1-expression in tumor-infiltrated tissue (skin, lypph node, etc) or peripheral blood by immunohistochemistry or PCR 4) (Only secondary registration) Having a donor who matches eligibility criteria 5) ECOG Performance Status, 0 ~ 2 6) Age >=20 years on consent 7) Life expectancy >= 12 weeks after consent 8) No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria; T. billirubin < 3 x ULN AST(GOT), ALT(GPT) < 5 x ULN Creatinine < 3 x ULN LVEF >=55% SpO2 >=94% 9) (only secondary registration) Completion of TBI-1301-A preparation 10) Ability to understand the study contents and to give a written consent at his/her free will Donor: 1) Original donor of hematopoetic stem cell transplantation 2) Age >=20 (20<= Age <=57, in case of an unrelated person coordinated by JMDP) years on consent 3) Ability to understand the study contents and to give a written consent at his/her free will
Key exclusion criteria	Patients: 1) The following serious complications are excluded from the study; Unstable angina, cardiac infarction, or heart failure Uncontrolled diabetes or hypertension Active infection Obvious interstitial pneumonia or lung fibrosis by chest X-ray Active autoimmune disease requiring steroids or immunosuppressive therapy 2) Serious hypersensitivity 3) Tumor cell invasion into CNS 4) Active multiple cancer 5) History of serious hypersensitivity reactions to bovine or murine derived substances, human serum albumin, streptomycin sulfate or amphotericin B 6) History of hypersensitivity reaction to drugs used in this study 7) Recurrence within 30 days after hematopoietic stem cell transplantation 8) GVHD >= Grade 3 (based on the guideline given JSHCT) 9) Uncontrollable pleural effusion, ascites or pericardial effusion 10) Antitumor therapy (chemotherapy, molecular targeted therapy, immunotherapy, radiation therapy, etc.) which are performed or will be performed within 4 weeks prior to the pre-treatment 11) Psycological disorder or drug dependency which may have impact on the consent 12) Pregnant females, lactating females (except when they cease and don't resume lactation) or female and male patients who cannot agree to practice the adequate birth control from the consent to at lease 6 months after the transfusion of TBI-1301-A 13) Any other inadequacy for this study Donor: 1) Positvity fo any of HBs antigen, HBV-DNA, HCV antibody, HCV-RNA, HIV antibody, HIV-RNA, serologic test of syphilis and parvovirus B19-DNA 2) Psycological disorder or drug dependency which may have impact on the consent 3) Any other inadequacy for this study
Target sample size	12

Research contact person
Name of lead principal investigator	1st name Hiroaki Middle name Last name Ikeda
Organization	Graduate School of Biomedical Sciences, Nagasaki University
Division name	Department of Oncology
Zip code	852-8523
Address	1-12-4 Sakamoto, Nagasaki-city, Nagasaki
TEL	095-819-7079
Email	hikeda@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Tatsushi Middle name Last name Goto
Organization	Secretariat of clinical trial coordinating committee
Division name	none
Zip code	530-0044
Address	Urban Ace Higashitenma-BLDG, 1-1-19, Higashitenma, Kita-ku, Osaka
TEL	06-6358-7110
Homepage URL
Email	gotou@fiverings.co.jp

Sponsor
Institute	Nagasaki University
Institute
Department

Funding Source
Organization	none
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Nagasaki University Hospital IRB
Address	1-7-1 Sakamoto, Nagasaki-city, Nagasaki, 852-8501, Japan
Tel	-
Email	-

Secondary IDs
Secondary IDs	YES
Study ID_1	JapicCTI-183830
Org. issuing International ID_1	Japan Pharmaceutical Information Center
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	獨協医科大学病院（栃木県）、東京大学医科学研究所附属病院（東京都）、名古屋市立大学病院（愛知県）、三重大学医学部附属病院（三重県）、大阪国際がんセンター（大阪府）、九州大学病院（福岡県）、長崎大学病院（長崎県）、鹿児島大学病院（鹿児島県）、今村総合病院（鹿児島県）

Other administrative information
Date of disclosure of the study information	2018 Year 03 Month 23 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	1
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	Terminated
Date of protocol fixation	2017 Year 09 Month 11 Day
Date of IRB	2017 Year 12 Month 22 Day
Anticipated trial start date	2018 Year 02 Month 01 Day
Last follow-up date	2021 Year 01 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 03 Month 23 Day
Last modified on	2021 Year 10 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035766