Clinical trial NCT03250325: Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients with Synovial Sarcoma
Official title: Multi-center Phase I/II Study of NY-ESO-1 T Cell Receptor Gene Transferred T Lymphocytes in Patients with Synovial Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Synovial Sarcoma
Keywords: Adoptive cell transfer
Cell therapy
Immunotherapy
NY-ESO-1
T cell receptor gene therapy
Synovial sarcoma
Lead sponsor: Takara Bio Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: (Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
timeFrame: 52 weeks
measure: (Phase I) Appearance of replication competent retrovirus (RCR) by PCR
timeFrame: 52 weeks
measure: (Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR
timeFrame: 52 weeks
measure: (Phase I) Blood kinetics of TBI-1301 by realtime-PCR
timeFrame: 52 weeks
measure: (Phase II) Overall response rate
timeFrame: 52 weeks
Secondary outcomes:
measure: (Phase I) Objective response rate
timeFrame: 52 weeks
measure: (Phase I/II) Progression free rate
timeFrame: 12 weeks
measure: (Phase I/II) Progression free survival
timeFrame: 52 weeks
measure: (Phase I/II) Overall survival
timeFrame: 52 weeks
measure: (Phase II) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
timeFrame: 52 weeks
measure: (Phase II) Appearance of RCR
timeFrame: 52 weeks
measure: (Phase II) Appearance of clonality (LAM-PCR)
timeFrame: 52 weeks
measure: (Phase II) Blood kinetics of TBI-1301 by realtime-PCR
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
Study officials:
affiliation: Takara Bio Inc.
name: Masanobu Kimura
role: STUDY_DIRECTOR
References: