UMIN-CTR Clinical Trial

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

Refractory ATLL experiencing recurrence after allogenic hematopoietic stem cell transplantation

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

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

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

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Nagasaki University

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Nagasaki University Hospital IRB

Address

1-7-1 Sakamoto, Nagasaki-city, Nagasaki, 852-8501, Japan

Tel

-

Email

-

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

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）

Date of disclosure of the study information

2018

Year

03

Month

23

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2018

Year

03

Month

23

Day

Last modified on

2021

Year

10

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035766