Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients with Synovial Sarcoma

NCT03250325 | Completed Phase 1 DMC

• 1 other identifier: 1301-03
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety and the efficacy of TBI-1301 for NY-ESO-1 expressing synovial sarcoma when administered following cyclophosphamide pre-treatment.

Conditions

Synovial Sarcoma

Keywords

Adoptive cell transfer; Cell therapy; Immunotherapy; NY-ESO-1; T cell receptor gene therapy; Synovial sarcoma

Outcome Measures

Primary Outcomes (5)

• (Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values

  Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.

  52 weeks

• (Phase I) Appearance of replication competent retrovirus (RCR) by PCR

  Confirm that no replication competent retrovirus observed.

  52 weeks

• (Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR

  Confirm that no clonality is observed.

  52 weeks

• (Phase I) Blood kinetics of TBI-1301 by realtime-PCR

  Evaluate persistence and expansion of transferred TBI-1301.

  52 weeks

• (Phase II) Overall response rate

  Evaluate response rate by measuring response using RECIST v1.1 and irRECIST

  52 weeks

Secondary Outcomes (8)

• (Phase I) Objective response rate

  52 weeks

• (Phase I/II) Progression free rate

  12 weeks

• (Phase I/II) Progression free survival

  52 weeks

• (Phase I/II) Overall survival

  52 weeks

• (Phase II) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values

  52 weeks

Study Arms (1)

Split dose of 5x10^9 TBI-1301

EXPERIMENTAL

Split dose of 5x10\^9 TBI-1301 will be administered intravenously for 2 days following cyclophosphamide pre-treatment 750 mg/m2/d for 2 days.

Biological: TBI-1301; Drug: Cyclophosphamide

Interventions

TBI-1301 BIOLOGICAL

Split dose of TBI-1301 is administered intravenously for 2 days following cyclophosphamide pre-treatment.

Split dose of 5x10^9 TBI-1301

Cyclophosphamide DRUG

Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.

Split dose of 5x10^9 TBI-1301

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed synovial sarcoma
• Surgically unresectable tumor
• Progressing or recurrent synovial sarcoma which has been treated with 1-4 regimens of systemic chemotherapies including anthracycline
• HLA-A\*02:01 or HLA-A\*02:06 positive
• Tumor that express NY-ESO-1 by immunohistochemistry
• ≥ 18 years of age
• Measurable lesions that are evaluable by the RECIST ver1.1
• ECOG Performance Status of 0, 1 or 2
• No treatment such as chemotherapy and be expected to recover fully from the previous treatment at the time of the lymphocytes collection for manufacturing
• Life expectancy ≥ 16 weeks after consent
• 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/μL \< WBC ≤ULN; Hemoglobin ≥ 8.0g/dL; Platelets ≥ 75,000/μL
• 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.

You may not qualify if:

• 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.
• Active metastatic tumor cell invasion into CNS
• Active multiple cancer
• Positive for HBs antigen or HBV-DNA observed in serum
• Positive for HCV antibody and HCV-RNA observed in serum
• Positive for antibodies against HIV or HTLV-1
• Left Ventricular Ejection Fraction (LVEF) ≤ 50%
• History of serious hypersensitivity reactions to bovine or murine derived substances.
• History of hypersensitivity reaction to ingredients or excipients of investigational drugs used in this study
• History of hypersensitivity reaction to antibiotics used in manufacturing for the investigational drug used in this study.
• 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.
• 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.

Sponsors & Collaborators

• Takara Bio Inc.: lead

Study Sites (5)

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, Osaka, 540-0006, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

MeSH Terms

Conditions

Sarcoma, Synovial

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Masanobu Kimura

  Takara Bio Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 15, 2017
• Study Start: September 20, 2017
• Primary Completion: January 23, 2020
• Study Completion: March 9, 2022
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

JP (5)