<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03250325</url>
  </required_header>
  <id_info>
    <org_study_id>1301-03</org_study_id>
    <nct_id>NCT03250325</nct_id>
  </id_info>
  <brief_title>Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients With Synovial Sarcoma</brief_title>
  <official_title>Multi-center Phase I/II Study of NY-ESO-1 T Cell Receptor Gene Transferred T Lymphocytes in Patients With Synovial Sarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Takara Bio Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takara Bio Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and the efficacy of TBI-1301 for NY-ESO-1&#xD;
      expressing synovial sarcoma when administered following cyclophosphamide pre-treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following pre-treatment with cyclophosphamide, NY-ESO-1-specific T cell receptor (TCR) gene&#xD;
      transduced T lymphocytes are transferred to human leukocyte antigen (HLA)-A*02:01 or&#xD;
      HLA-A*02:06 positive patients with synovial sarcoma expressing NY-ESO-1, which are surgically&#xD;
      unresectable and refractory to anthracycline therapy. The primary objective is to evaluate&#xD;
      the safety in the phase 1 and the efficacy in the phase 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 20, 2017</start_date>
  <completion_date type="Anticipated">January 2034</completion_date>
  <primary_completion_date type="Actual">January 23, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>(Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase I) Appearance of replication competent retrovirus (RCR) by PCR</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm that no replication competent retrovirus observed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm that no clonality is observed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase I) Blood kinetics of TBI-1301 by realtime-PCR</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate persistence and expansion of transferred TBI-1301.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>(Phase II) Overall response rate</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate response rate by measuring response using RECIST v1.1 and irRECIST</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>(Phase I) Objective response rate</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate response rate by measuring response using RECIST v1.1 and irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase I/II) Progression free rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Evaluate progression free rate by measuring response using RECIST v1.1 and irRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase I/II) Progression free survival</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate progression free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase I/II) Overall survival</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase II) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase II) Appearance of RCR</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm that no replication competent retrovirus observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase II) Appearance of clonality (LAM-PCR)</measure>
    <time_frame>52 weeks</time_frame>
    <description>Confirm that no clonality is observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Phase II) Blood kinetics of TBI-1301 by realtime-PCR</measure>
    <time_frame>52 weeks</time_frame>
    <description>Evaluate persistence and expansion of transferred TBI-1301.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">8</enrollment>
  <condition>Synovial Sarcoma</condition>
  <arm_group>
    <arm_group_label>Split dose of 5x10^9 TBI-1301</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TBI-1301</intervention_name>
    <description>Split dose of TBI-1301 is administered intravenously for 2 days following cyclophosphamide pre-treatment.</description>
    <arm_group_label>Split dose of 5x10^9 TBI-1301</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.</description>
    <arm_group_label>Split dose of 5x10^9 TBI-1301</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed synovial sarcoma&#xD;
&#xD;
          2. Surgically unresectable tumor&#xD;
&#xD;
          3. Progressing or recurrent synovial sarcoma which has been treated with 1-4 regimens of&#xD;
             systemic chemotherapies including anthracycline&#xD;
&#xD;
          4. HLA-A*02:01 or HLA-A*02:06 positive&#xD;
&#xD;
          5. Tumor that express NY-ESO-1 by immunohistochemistry&#xD;
&#xD;
          6. ≥ 18 years of age&#xD;
&#xD;
          7. Measurable lesions that are evaluable by the RECIST ver1.1&#xD;
&#xD;
          8. ECOG Performance Status of 0, 1 or 2&#xD;
&#xD;
          9. No treatment such as chemotherapy and be expected to recover fully from the previous&#xD;
             treatment at the time of the lymphocytes collection for manufacturing&#xD;
&#xD;
         10. Life expectancy ≥ 16 weeks after consent&#xD;
&#xD;
         11. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc)&#xD;
             and meet the following lab value criteria; Total bilirubin ≤ 1.5 x upper limit of&#xD;
             normal (ULN); AST(GOT), ALT(GPT) &lt; 3.0 x ULN; Creatinine &lt; 1.5 x ULN; 2,500/μL &lt; WBC&#xD;
             ≤ULN; Hemoglobin ≥ 8.0g/dL; Platelets ≥ 75,000/μL&#xD;
&#xD;
         12. Patients must be able to understand the study contents and to give a written consent&#xD;
             at his/her free will. Additionally, if patients are below 20 years of age, proxies&#xD;
             must be able to give a written consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with the following conditions are excluded from the study; Unstable angina,&#xD;
             cardiac infarction, or heart failure; Uncontrolled diabetes or hypertension; Active&#xD;
             infection; Obvious interstitial pneumonia or lung fibrosis by chest X-ray; Active&#xD;
             autoimmune disease requiring steroids or immunosuppressive therapy.&#xD;
&#xD;
          2. Active metastatic tumor cell invasion into CNS&#xD;
&#xD;
          3. Active multiple cancer&#xD;
&#xD;
          4. Positive for HBs antigen or HBV-DNA observed in serum&#xD;
&#xD;
          5. Positive for HCV antibody and HCV-RNA observed in serum&#xD;
&#xD;
          6. Positive for antibodies against HIV or HTLV-1&#xD;
&#xD;
          7. Left Ventricular Ejection Fraction (LVEF) ≤ 50%&#xD;
&#xD;
          8. History of serious hypersensitivity reactions to bovine or murine derived substances.&#xD;
&#xD;
          9. History of hypersensitivity reaction to ingredients or excipients of investigational&#xD;
             drugs used in this study&#xD;
&#xD;
         10. History of hypersensitivity reaction to antibiotics used in manufacturing for the&#xD;
             investigational drug used in this study.&#xD;
&#xD;
         11. Pregnant females, lactating females (except when they cease and do not resume&#xD;
             lactation) or female and male patients who cannot agree to practice the adequate birth&#xD;
             control from the consent to 6 months after infusion of the investigational drug.&#xD;
&#xD;
         12. Clinically significant systemic illness that in the judgment of the PI or&#xD;
             sub-investigator would compromise the patient's ability to tolerate protocol therapy&#xD;
             or significantly increase the risk of complications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Masanobu Kimura</last_name>
    <role>Study Director</role>
    <affiliation>Takara Bio Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sapporo Medical University Hospital</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>060-8543</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mie University Hospital</name>
      <address>
        <city>Tsu</city>
        <state>Mie</state>
        <zip>514-8507</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyushu University Hospital</name>
      <address>
        <city>Fukuoka</city>
        <zip>812-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Osaka National Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>June 1, 2022</last_update_submitted>
  <last_update_submitted_qc>June 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adoptive cell transfer</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>NY-ESO-1</keyword>
  <keyword>T cell receptor gene therapy</keyword>
  <keyword>Synovial sarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Sarcoma, Synovial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03250325
org study id: 1301-03
nct id: NCT03250325
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: (Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
time frame: 52 weeks
description: Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
measure: (Phase I) Appearance of replication competent retrovirus (RCR) by PCR
time frame: 52 weeks
description: Confirm that no replication competent retrovirus observed.
measure: (Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR
time frame: 52 weeks
description: Confirm that no clonality is observed.
measure: (Phase I) Blood kinetics of TBI-1301 by realtime-PCR
time frame: 52 weeks
description: Evaluate persistence and expansion of transferred TBI-1301.
measure: (Phase II) Overall response rate
time frame: 52 weeks
description: Evaluate response rate by measuring response using RECIST v1.1 and irRECIST
measure: (Phase I) Objective response rate
time frame: 52 weeks
description: Evaluate response rate by measuring response using RECIST v1.1 and irRECIST
measure: (Phase I/II) Progression free rate
time frame: 12 weeks
description: Evaluate progression free rate by measuring response using RECIST v1.1 and irRECIST
measure: (Phase I/II) Progression free survival
time frame: 52 weeks
description: Evaluate progression free survival
measure: (Phase I/II) Overall survival
time frame: 52 weeks
description: Evaluate overall survival
measure: (Phase II) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
time frame: 52 weeks
description: Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
measure: (Phase II) Appearance of RCR
time frame: 52 weeks
description: Confirm that no replication competent retrovirus observed.
measure: (Phase II) Appearance of clonality (LAM-PCR)
time frame: 52 weeks
description: Confirm that no clonality is observed.
measure: (Phase II) Blood kinetics of TBI-1301 by realtime-PCR
time frame: 52 weeks
description: Evaluate persistence and expansion of transferred TBI-1301.
arm group label: Split dose of 5x10^9 TBI-1301
arm group type: Experimental
description: 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.
intervention type: Biological
intervention name: TBI-1301
description: Split dose of TBI-1301 is administered intravenously for 2 days following cyclophosphamide pre-treatment.
arm group label: Split dose of 5x10^9 TBI-1301
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.
arm group label: Split dose of 5x10^9 TBI-1301
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Masanobu Kimura
role: Study Director
affiliation: Takara Bio Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Sarcoma, Synovial
mesh term: Cyclophosphamide
sharing ipd: Undecided