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.
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
Interventions
Drug | Synonyms | Arms |
---|
TBI-1301 | | Split dose of 5x10^9 TBI-1301 |
Cyclophosphamide | | Split 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
Name | Type | Description | Interventions |
---|
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. | |
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: | Active, not recruiting |
Lead Sponsor: | Takara Bio Inc. |
Trial Keywords
- Adoptive cell transfer
- Cell therapy
- Immunotherapy
- NY-ESO-1
- T cell receptor gene therapy
- Synovial sarcoma
Last Updated
October 8, 2020