Clinical Trials /

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

NCT03250325

Description:

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.

Related Conditions:
  • Synovial Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 1301-03
  • NCT ID: NCT03250325

Conditions

  • Synovial Sarcoma

Interventions

DrugSynonymsArms
TBI-1301Split dose of 5x10^9 TBI-1301
CyclophosphamideSplit dose of 5x10^9 TBI-1301

Purpose

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.
    

Trial Arms

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

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:(Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values
Time Frame:52 weeks
Safety Issue:
Description:Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Takara Bio Inc.

Trial Keywords

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

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