Back to resultsA Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma (NY-ESO-1)
Primary Purpose
Neoplasms
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NY-ESO-1(c259)T Cells
Fludarabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring T Cell Receptor, Sarcoma, Cell Therapy, T Cell Therapy, Previously treated, NY-ESO-1, Metastatic, Immuno-oncology
Eligibility Criteria
Inclusion Criteria:
- Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
- Measurable disease
Patients must have proven positive tumor sample for NY-ESO-1 as follows:
- Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
- Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 by high resolution testing at a local or central laboratory
- Weigh more than 18 kg
- All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
- Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
- Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
- Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
- ECOG 0-1, or for children ≤10 years of age, Lansky > 60
- Life expectancy > 3 months
- Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
- T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome total bilirubin <3xULN and direct bilirubin ≤ 35%)
- AST, ALT ≤ 2.5 x upper limit of normal
- ANC ≥ 1.0 x 10⁹/L
- Platelets ≥ 75 x 10⁹/L
- Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
- Ability to give informed consent for patients greater than 18 years of age. For patients less than 18 years of age the legal guardian must give informed consent.
- Male patients must be willing to practice birth control (including abstinence) during and for 4 months after treatment. Female patients must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.
Exclusion Criteria:
- Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1 treated with NY-ESO-1 T Cells
Cohort 2 treated with NY-ESO-1 T Cells
Cohort 3 treated with NY-ESO-1 T Cells
Cohort 4 treated with NY-ESO-1 T Cells
Arm Description
High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.
Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.
High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy.
High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by the local investigators.
Secondary Outcome Measures
Duration of Overall Response
Duration of overall response (DOR) is defined as the time from first documented evidence of confirmed CR or confirmed PR until first documented date of disease progression or death due to any cause or surgical resection or start of prohibited medications. Duration of overall response was evaluated per RECIST v1.1. Median and full range of DOR are presented.
Progression Free Survival
Progression free survival is defined as the interval between the date of first T cell infusion and the earliest documented evidence of disease progression or death due to any cause or surgical resection or start of prohibited medications. Progression free survival was evaluated per RECIST v1.1. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
Best Overall Response
Best overall response is the best response recorded from the start of treatment (first T cell infusion) until disease progression/recurrence. Response categories from best to worst are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD). Best overall response is a stable disease, if CR or PR are unconfirmed. Data for number of participants with CR, PR, SD and PD are presented.
Overall Survival
Overall survival is defined as the interval between the date of the first T-cell infusion and date of death from any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had non-SAEs and SAEs are presented.
Number of Participants With Worst Post-Baseline Grade Results for Hematology Parameters
Blood samples were collected for the analysis of hematology parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.
Number of Participants With Worst Post-Baseline Grade Results for Clinical Chemistry Parameters
Blood samples were collected for the analysis of clinical chemistry parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.
Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result
Serum samples were collected for the determination of anti-infused (NY-ESO-1 genetically engineered T) cell antibodies (ATA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. A participant was considered to have a confirmed positive ATA result if they have a positive screening assay result and a positive confirmation assay result.
Concentration of Cytokines in Cytokine Release Syndrome (CRS) by CRS Status: Cohort 1: High NY-ESO-1 Expression Treated With Regimen A
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Concentration of Cytokines in CRS by CRS Status: Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Concentration of Cytokines in CRS by CRS Status: Cohort 3: High NY-ESO-1 Expression Treated With Regimen B
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Concentration of Cytokines in CRS by CRS Status: Cohort 4: High NY-ESO-1 Expression Treated With Regimen C
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells
Time to maximum persistence is defined as date of maximum persistence for infusion visit minus date of first T cell infusion visit plus 1. Median and full range of time to maximum persistence are presented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01343043
Brief Title
A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Acronym
NY-ESO-1
Official Title
A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
September 27, 2012 (Actual)
Primary Completion Date
June 18, 2019 (Actual)
Study Completion Date
June 18, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and adoptive immunotherapy with T cells engineered to recognize NY-ESO-1 peptide in patients with unresectable, metastatic or recurrent synovial sarcoma.
Detailed Description
Design
Patients will undergo apheresis at the enrolling institution. PBMC will be shipped to a central manufacturer for gene transduction, activation and expansion, then cryopreserved and shipped back to the enrolling institution.
The trial seeks to enroll up to 65 patients, that is, up to 20 patients in Cohort 1 and up to 15 patients in Cohorts 2-4. Depending on the cohort patients are enrolled in, patients will undergo lymphodepletion with cyclophosphamide with or without fludarabine.
Cohort 1: Complete
Cohort 2: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -3 and -2, and without fludarabine on Days -5 and -4.
Cohort 3: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide only on Days -3 and -2. (Cohort Complete)
Cohort 4: Up to 15 patients may be enrolled to achieve at least 5 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -7 to -5.
On Day 0, patients ≥40 kg will receive the minimum cell dose of at least 1x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells with a maximum of 6x10⁹ transduced cells. The target dose for this protocol is 5x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells. Patients <40 kg will be dosed per body weight with a minimum 0.025x10⁹ transduced cells/kg, with a target dose of 0.125 x10⁹ transduced cells/kg.
Patients will be monitored for toxicity, antitumor effects and immune endpoints.
Patients who have a confirmed response, or have stable disease for >3 months then progress may receive a 2nd T cell infusion, provided eligibility criteria are met. The 2nd treatment cell infusion will be administered in the same manner as the first. Patients who meet the eligibility criteria may receive a 2nd infusion of NY-ESO-1ᶜ²⁵⁹T no sooner than 60 days and no later than 2 years following completion of the first treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
T Cell Receptor, Sarcoma, Cell Therapy, T Cell Therapy, Previously treated, NY-ESO-1, Metastatic, Immuno-oncology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 treated with NY-ESO-1 T Cells
Arm Type
Experimental
Arm Description
High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.
Arm Title
Cohort 2 treated with NY-ESO-1 T Cells
Arm Type
Experimental
Arm Description
Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy.
Arm Title
Cohort 3 treated with NY-ESO-1 T Cells
Arm Type
Experimental
Arm Description
High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy.
Arm Title
Cohort 4 treated with NY-ESO-1 T Cells
Arm Type
Experimental
Arm Description
High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
NY-ESO-1(c259)T Cells
Intervention Description
Lymphodepleting chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine will be used as lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be used as lymphodepleting chemotherapy.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1 as determined by the local investigators.
Time Frame
Up to 4.5 years
Secondary Outcome Measure Information:
Title
Duration of Overall Response
Description
Duration of overall response (DOR) is defined as the time from first documented evidence of confirmed CR or confirmed PR until first documented date of disease progression or death due to any cause or surgical resection or start of prohibited medications. Duration of overall response was evaluated per RECIST v1.1. Median and full range of DOR are presented.
Time Frame
Up to 4.5 years
Title
Progression Free Survival
Description
Progression free survival is defined as the interval between the date of first T cell infusion and the earliest documented evidence of disease progression or death due to any cause or surgical resection or start of prohibited medications. Progression free survival was evaluated per RECIST v1.1. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
Time Frame
Up to 4.5 years
Title
Best Overall Response
Description
Best overall response is the best response recorded from the start of treatment (first T cell infusion) until disease progression/recurrence. Response categories from best to worst are confirmed CR, confirmed PR, stable disease (SD) and confirmed progressive disease (PD). Best overall response is a stable disease, if CR or PR are unconfirmed. Data for number of participants with CR, PR, SD and PD are presented.
Time Frame
Up to 4.5 years
Title
Overall Survival
Description
Overall survival is defined as the interval between the date of the first T-cell infusion and date of death from any cause. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented.
Time Frame
Up to 4.5 years
Title
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Description
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had non-SAEs and SAEs are presented.
Time Frame
Up to 5 years
Title
Number of Participants With Worst Post-Baseline Grade Results for Hematology Parameters
Description
Blood samples were collected for the analysis of hematology parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.
Time Frame
Up to 4.5 years
Title
Number of Participants With Worst Post-Baseline Grade Results for Clinical Chemistry Parameters
Description
Blood samples were collected for the analysis of clinical chemistry parameters. No data collected separately for this outcome measure as any abnormal value would be recorded as an adverse event.
Time Frame
Up to 4.5 years
Title
Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result
Description
Serum samples were collected for the determination of anti-infused (NY-ESO-1 genetically engineered T) cell antibodies (ATA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. A participant was considered to have a confirmed positive ATA result if they have a positive screening assay result and a positive confirmation assay result.
Time Frame
Up to 4.5 years
Title
Concentration of Cytokines in Cytokine Release Syndrome (CRS) by CRS Status: Cohort 1: High NY-ESO-1 Expression Treated With Regimen A
Description
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Time Frame
Up to Week 4
Title
Concentration of Cytokines in CRS by CRS Status: Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A
Description
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Time Frame
Up to Week 4
Title
Concentration of Cytokines in CRS by CRS Status: Cohort 3: High NY-ESO-1 Expression Treated With Regimen B
Description
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Time Frame
Up to Week 4
Title
Concentration of Cytokines in CRS by CRS Status: Cohort 4: High NY-ESO-1 Expression Treated With Regimen C
Description
CRS is a potentially life-threatening toxicity that is observed following administration of antibodies and adoptive T-cell therapies for cancer. Serum samples were collected to analyze the concentration of cytokines using the electrochemiluminescent tagged detection antibodies. The correlation between cytokines and cytokine release syndrome was considered between participants who had serious CRS vs no CRS or Non-serious CRS. There were only 4 participants across the whole study that had serious CRS and cytokine data was available for 3 of these participants. Due to the limited number of participants that had serious CRS no statistical correlations in cytokine levels and CRS could be performed. A listing of the levels of cytokines for the 3 participants with serious CRS is available/provided.
Time Frame
Up to Week 4
Title
Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells
Description
Time to maximum persistence is defined as date of maximum persistence for infusion visit minus date of first T cell infusion visit plus 1. Median and full range of time to maximum persistence are presented.
Time Frame
Up to 4.5 years
Other Pre-specified Outcome Measures:
Title
Number of Participants With Dose-limiting Toxicities (DLTs)
Description
DLT was planned to be evaluated. An event was to be considered a DLT if it occurred within the first 21 days of treatment, and met one of the protocol defined DLT criteria. The results for this outcome measure will never be posted.
Time Frame
Up to Day 21 (from first dose)
Title
Number of Participants With Clinically Significant Abnormal Electrocardiogram, Echocardiogram and Multigated Acquisition Scan Findings
Description
Abnormal electrocardiogram, echocardiogram and multigated acquisition scan findings were planned to be evaluated. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. The results for this outcome measure will never be posted.
Time Frame
Up to 4.5 years
Title
Percentage of Participants With Confirmed CR
Description
Participants were planned to be evaluated for confirmed CR according to RECIST v1.1, after receiving a second dose of NY-ESO-1 genetically engineered T cell infusion. The results for this outcome measure will never be posted.
Time Frame
Up to 4.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
Measurable disease
Patients must have proven positive tumor sample for NY-ESO-1 as follows:
Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 by high resolution testing at a local or central laboratory
Weigh more than 18 kg
All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
ECOG 0-1, or for children ≤10 years of age, Lansky > 60
Life expectancy > 3 months
Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome total bilirubin <3xULN and direct bilirubin ≤ 35%)
AST, ALT ≤ 2.5 x upper limit of normal
ANC ≥ 1.0 x 10⁹/L
Platelets ≥ 75 x 10⁹/L
Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
Ability to give informed consent for patients greater than 18 years of age. For patients less than 18 years of age the legal guardian must give informed consent.
Male patients must be willing to practice birth control (including abstinence) during and for 4 months after treatment. Female patients must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.
Exclusion Criteria:
Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
GSK Investigational Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
GSK Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
36075914
Citation
Gyurdieva A, Zajic S, Chang YF, Houseman EA, Zhong S, Kim J, Nathenson M, Faitg T, Woessner M, Turner DC, Hasan AN, Glod J, Kaplan RN, D'Angelo SP, Araujo DM, Chow WA, Druta M, Demetri GD, Van Tine BA, Grupp SA, Fine GD, Eleftheriadou I. Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma. Nat Commun. 2022 Sep 8;13(1):5296. doi: 10.1038/s41467-022-32491-x.
Results Reference
derived
PubMed Identifier
31651363
Citation
Ramachandran I, Lowther DE, Dryer-Minnerly R, Wang R, Fayngerts S, Nunez D, Betts G, Bath N, Tipping AJ, Melchiori L, Navenot JM, Glod J, Mackall CL, D'Angelo SP, Araujo DM, Chow WA, Demetri GD, Druta M, Van Tine BA, Grupp SA, Abdul Razak AR, Wilky B, Iyengar M, Trivedi T, Winkle EV, Chagin K, Amado R, Binder GK, Basu S. Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma. J Immunother Cancer. 2019 Oct 24;7(1):276. doi: 10.1186/s40425-019-0762-2.
Results Reference
derived
PubMed Identifier
29891538
Citation
D'Angelo SP, Melchiori L, Merchant MS, Bernstein D, Glod J, Kaplan R, Grupp S, Tap WD, Chagin K, Binder GK, Basu S, Lowther DE, Wang R, Bath N, Tipping A, Betts G, Ramachandran I, Navenot JM, Zhang H, Wells DK, Van Winkle E, Kari G, Trivedi T, Holdich T, Pandite L, Amado R, Mackall CL. Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 c259T Cells in Synovial Sarcoma. Cancer Discov. 2018 Aug;8(8):944-957. doi: 10.1158/2159-8290.CD-17-1417. Epub 2018 Jun 11.
Results Reference
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A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
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