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

Synovial Sarcoma Clinical Trial

Official title:

Multi-center Phase I/II Study of NY-ESO-1 T Cell Receptor Gene Transferred T Lymphocytes in Patients With Synovial Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03250325
• Other study ID #: 1301-03
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 20, 2017
• Est. completion date: March 9, 2022

Study information

• Verified date: December 2023
• Source: Takara Bio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Following pre-treatment with cyclophosphamide, NY-ESO-1-specific T cell receptor (TCR) gene transduced T lymphocytes are transferred to human leukocyte antigen (HLA)-A*02:01 or HLA-A*02:06 positive patients with synovial sarcoma expressing NY-ESO-1, which are surgically unresectable and refractory to anthracycline therapy. The primary objective is to evaluate the safety in the phase 1 and the efficacy in the phase 2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 9, 2022
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 anthracycline

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 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/µL < WBC =ULN; Hemoglobin = 8.0g/dL; Platelets = 75,000/µL

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.

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.

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

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

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

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Mie University Hospital	Tsu	Mie

Sponsors (1)

Lead Sponsor	Collaborator
Takara Bio Inc.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	(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
Primary	(Phase I) Appearance of replication competent retrovirus (RCR) by PCR	Confirm that no replication competent retrovirus observed.	52 weeks
Primary	(Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR	Confirm that no clonality is observed.	52 weeks
Primary	(Phase I) Blood kinetics of TBI-1301 by realtime-PCR	Evaluate persistence and expansion of transferred TBI-1301.	52 weeks
Primary	(Phase II) Overall response rate	Evaluate response rate by measuring response using RECIST v1.1 and irRECIST	52 weeks
Secondary	(Phase I) Objective response rate	Evaluate response rate by measuring response using RECIST v1.1 and irRECIST	52 weeks
Secondary	(Phase I/II) Progression free rate	Evaluate progression free rate by measuring response using RECIST v1.1 and irRECIST	12 weeks
Secondary	(Phase I/II) Progression free survival	Evaluate progression free survival	52 weeks
Secondary	(Phase I/II) Overall survival	Evaluate overall survival	52 weeks
Secondary	(Phase II) 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
Secondary	(Phase II) Appearance of RCR	Confirm that no replication competent retrovirus observed.	52 weeks
Secondary	(Phase II) Appearance of clonality (LAM-PCR)	Confirm that no clonality is observed.	52 weeks
Secondary	(Phase II) Blood kinetics of TBI-1301 by realtime-PCR	Evaluate persistence and expansion of transferred TBI-1301.	52 weeks