UMIN-CTR Clinical Trial

Public title

Multi-center Phase I/II Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes following chemotherapy pre-treatment in Patients with Synovial Sarcoma

Acronym

Phase I/II Study of TBI-1301 in Patients with Synovial Sarcoma

Scientific Title

Multi-center Phase I/II Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes following chemotherapy pre-treatment in Patients with Synovial Sarcoma

Scientific Title:Acronym

Phase I/II Study of TBI-1301 in Patients with Synovial Sarcoma

Region

Japan

Condition

Synovial sarcoma

Classification by specialty

Orthopedics

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

The efficacy and the safety of TBI-1301 (NY-ESO-1 specifc TCR gene transferred autologous T lymphocytes) are evaluated in HLA-A*02:01 or HLA-A*02:06 positive patients with relapsed synovial sarcoma, which are surgically unresectable, refractory to anthracycline therapy, and NY-ESO-1-expressing.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

[Phase I portion]
Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
Appearance of clonality by LAM-PCR
Blood kinetics of TBI-1301 by realtime-PCR

[Phase II portion]
Overall response rate

Key secondary outcomes

[Phase I portion]
Objective response rate
Progression free rate at week 12
Progression free survival
Overall survival

[Phase II portion]
Progression free rate
Progression free survival
Overall survival
Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
Appearance of RCR
Appearance of clonality (LAM-PCR)
Blood kinetics of TBI-1301

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Gene

Interventions/Control_1

As pretreatment, Cyclophosphamide (750 mg/m2) is administered intravenously once a day on day -3 and -2 for 2 days. Split dose of TBI-1301 (5 x 10^9 cells [+-30%]) is administered intravenously on day 0 and 1 for 2 days.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Histologically confirmed synovial sarcoma
2) Surgically unresectable tumor
3) Progressing or recurrent synovial sarcoma which has been treated with 1-4 regimens of systemic chemotherapies including anthracyclin
4) HLA-A*02:01 or HLA-A*02:06 positive
5) Tumor that express NY-ESO-1 by immunohistochemistry
6) >= 18 years of age
7) Measurable lesions that are expected to be evaluable by the RECIST ver1.1
8) ECOG Performance Status of 0, 1 or 2
9) No treatment such as chemotherapy and be expected to recover fully from the previous treatment at the time of the lymphocytes collection for manufacturing
10) Life expectancy >= 16 weeks after consent
11) No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria;
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- AST(GOT), ALT(GPT) < 3.0 x ULN
- Creatinine < 1.5 x ULN
- 2,500/microL < WBC =< ULN
- Hemoglobin >= 8.0g/dL
- Platelets >= 75,000/microL
12) Patients must be able to understand the study contents and to give a written consent at his/her free will. Additionally, if patients are below 20 years of age, proxies must be able to give a written consent.

Key exclusion criteria

1) Patients with the following conditions 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) Active metastatic tumor cell invasion into CNS
3) Active multiple cancer
4) Positive for HBs antigen or HBV-DNA observed in serum
5) Positive for HCV antibody and HCV-RNA observed in serum
6) Positive for antibodies against HIV or HTLV-1
7) Left Ventricular Ejection Fraction (LVEF) =< 50%
8) History of serious hypersensitivity reactions to bovine or murine derived substances.
9) History of hypersensitivity reaction to ingredients or excipients of investigational drugs used in this study
10) History of hypersensitivity reaction to antibiotics used in manufacturing for the investigational drug used in this study.
11) Pregnant females, lactating females (except when they cease and do not resume lactation) or female and male patients who cannot agree to practice the adequate birth control from the consent to 6 months after infusion of the investigational drug.
12) Clinically significant systemic illness that in the judgment of the PI or sub-investigator would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.

Target sample size

8

Name of lead principal investigator

1st name	Shuichi
Middle name
Last name	Takahashi

Organization

Takara Bio Inc.

Division name

Regenerative Medical Products Manufacturing

Zip code

525-0058

Address

Nojihigashi 7-4-38, Kusatsu, Shiga, Japan

TEL

077-565-6976

Email

takahashisz@takara-bio.co.jp

Name of contact person

1st name	NA
Middle name
Last name	NA

Organization

Takara Bio Inc.

Division name

Corporate Development

Zip code

525-0058

Address

Nojihigashi 7-4-38, Kusatsu, Shiga, Japan

TEL

077-565-6970

Homepage URL

Email

takara-clinical@takara-bio.co.jp

Institute

Takara Bio Inc.

Institute

Department

Personal name

Organization

Takara Bio Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Mie University Hospital IRB

Address

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

Tel

059-231-5246

Email

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

Secondary IDs

YES

Study ID_1

JapicCTI-173514

Org. issuing International ID_1

Japan Pharmaceutical Information Center

Study ID_2

NCT03250325

Org. issuing International ID_2

U.S. National Library of Medicine

IND to MHLW

Institutions

三重大学医学部附属病院（三重県）、国立病院機構大阪医療センター（大阪府）、札幌医科大学附属病院（北海道）、九州大学病院（福岡県）、国立がん研究センター中央病院（東京都）

Date of disclosure of the study information

2017

Year

10

Month

16

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/37792433/

Number of participants that the trial has enrolled

8

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

2017

Year

05

Month

13

Day

Date of IRB

2017

Year

08

Month

16

Day

Anticipated trial start date

2017

Year

09

Month

20

Day

Last follow-up date

2034

Year

01

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

10

Month

16

Day

Last modified on

2023

Year

10

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033661