Back to resultsLetetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
Primary Purpose
Neoplasms
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
letetresgene autoleucel (GSK3377794)
Cyclophosphamide
Fludarabine
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring Myxoid/ round cell liposarcoma, Letetresgene autoleucel, Immuno-oncology, T Cell Receptor, Leukapheresis, NY-ESO-1, Adoptive TCR T-cell therapy
Eligibility Criteria
Inclusion Criteria:
- Participant is greater than equal to (>=)18 years of age at the time of signing the study informed consent.
- Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12).
- Participant has measurable disease according to RECIST v1.1 criteria.
- Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
- Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
- Participant must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
- Participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for NY-ESO-1 expression by a designated central laboratory.
- Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
- Participant has a left ventricular ejection fraction >=45%.
- Participant is fit for apheresis and has adequate venous access for the cell collection.
- Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.
Exclusion Criteria:
- Any previous gene therapy using an integrating vector.
- Any previous allogeneic hematopoietic stem cell transplant.
- Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
- Participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
- Participant has known active brain or leptomeningeal metastases.
- Participant has other prior malignancy that is not in complete remission.
- Participant has uncontrolled intercurrent illness including, but not limited to:
- (i) Ongoing or active infection.
- (ii) Clinically significant cardiac disease
- (iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
- Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).
Sites / Locations
- 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 Type
Experimental
Arm Label
letetresgene autoleucel (GSK3377794)
Arm Description
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST v1.1 Criteria.
Secondary Outcome Measures
Time to Response (TTR) Assessed by Investigator
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
Duration of Response (DOR) Assessed by Investigator
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Progression Free Survival (PFS) Assessed by Investigator
Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment
The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by independent reviewer per RECIST v1.1 criteria.
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer
Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via independent reviewer assessment per RECIST v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Time to Response (TTR) Assessed by Independent Reviewer
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
Duration of Response (DOR) Assessed by Independent Reviewer
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Progression Free Survival (PFS) Assessed by Independent Reviewer
Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by independent reviewer per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth or is medically significant or requires intervention to prevent one or the outcomes listed above.
Number of Participants With Adverse Event of Special Interest (AESI)
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. The AESI included events of Cytokine release syndrome (CRS), Haematopoietic cytopenias (including pancytopenia and aplastic anaemia), Graft versus host disease (GvHD), Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS), and Guillain-Barre syndrome.
Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets, leukocytes. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline
Blood samples were collected for the analysis clinical chemistry parameters: glucose, albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, sodium, phosphate, calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Number of Participants With Replication Competent Lentivirus (RCL)
RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and measures copies of the gene coding for the vector's envelope protein, namely vesicular stomatitis virus G protein (VSV-G).
Number of Participants With Insertional Oncogenesis
Peripheral blood mononuclear cells (PBMC) samples were collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood. DNA from participant identified with >1% PBMC at >=1 year post T-cell infusion was sent for integration site analysis. Integration site analysis was used to assess the possibility of insertional oncogenesis. Participants with insertional oncogenesis were participants with any clones representing >20% of the total.
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Serum samples were collected to analyze for the presence of ADAs using validated immunoassays.
Maximum Transgene Expansion (Cmax) of GSK3377794
Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
Time to Cmax (Tmax)
Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.
Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794
Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).
Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
Triplicate 12-Lead ECGs were collected at baseline visit and single ECGs at other timepoints. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.
Change From Baseline in ECG Mean Heart Rate
Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02992743
Brief Title
Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
Official Title
A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
December 6, 2016 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
March 22, 2022 (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
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
Detailed Description
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
Myxoid/ round cell liposarcoma, Letetresgene autoleucel, Immuno-oncology, T Cell Receptor, Leukapheresis, NY-ESO-1, Adoptive TCR T-cell therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
letetresgene autoleucel (GSK3377794)
Arm Type
Experimental
Arm Description
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
letetresgene autoleucel (GSK3377794)
Intervention Description
Letetresgene autoleucel (GSK3377794) as an IV infusion.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine will be used as a lymphodepleting chemotherapy.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Description
Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Time Frame
Up to 24 months
Title
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Description
The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST v1.1 Criteria.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Time to Response (TTR) Assessed by Investigator
Description
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
Time Frame
Up to 24 months
Title
Duration of Response (DOR) Assessed by Investigator
Description
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Time Frame
Up to 24 months
Title
Progression Free Survival (PFS) Assessed by Investigator
Description
Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Time Frame
Up to 24 months
Title
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment
Description
The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by independent reviewer per RECIST v1.1 criteria.
Time Frame
Up to 24 months
Title
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer
Description
Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via independent reviewer assessment per RECIST v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Time Frame
Up to 24 months
Title
Time to Response (TTR) Assessed by Independent Reviewer
Description
Time to response was defined as the interval of time between the date of T-cell infusion and the first documented evidence of the confirmed response (PR or CR), in the subset of participants with a confirmed PR or CR as their best confirmed overall response. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.
Time Frame
Up to 24 months
Title
Duration of Response (DOR) Assessed by Independent Reviewer
Description
Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Time Frame
Up to 24 months
Title
Progression Free Survival (PFS) Assessed by Independent Reviewer
Description
Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by independent reviewer per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.
Time Frame
Up to 24 months
Title
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth or is medically significant or requires intervention to prevent one or the outcomes listed above.
Time Frame
Up to 24 months
Title
Number of Participants With Adverse Event of Special Interest (AESI)
Description
An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. The AESI included events of Cytokine release syndrome (CRS), Haematopoietic cytopenias (including pancytopenia and aplastic anaemia), Graft versus host disease (GvHD), Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS), and Guillain-Barre syndrome.
Time Frame
Up to 24 months
Title
Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline
Description
Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets, leukocytes. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Time Frame
Up to 24 months
Title
Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline
Description
Blood samples were collected for the analysis clinical chemistry parameters: glucose, albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, sodium, phosphate, calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.
Time Frame
Up to 24 months
Title
Number of Participants With Replication Competent Lentivirus (RCL)
Description
RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and measures copies of the gene coding for the vector's envelope protein, namely vesicular stomatitis virus G protein (VSV-G).
Time Frame
Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion
Title
Number of Participants With Insertional Oncogenesis
Description
Peripheral blood mononuclear cells (PBMC) samples were collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood. DNA from participant identified with >1% PBMC at >=1 year post T-cell infusion was sent for integration site analysis. Integration site analysis was used to assess the possibility of insertional oncogenesis. Participants with insertional oncogenesis were participants with any clones representing >20% of the total.
Time Frame
Up to 2 years
Title
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Description
Serum samples were collected to analyze for the presence of ADAs using validated immunoassays.
Time Frame
Up to 24 Months
Title
Maximum Transgene Expansion (Cmax) of GSK3377794
Description
Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
Time Frame
Day 2 to Day 15
Title
Time to Cmax (Tmax)
Description
Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.
Time Frame
Day 2 to Day 15
Title
Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794
Description
Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).
Time Frame
Up to 28 days
Title
Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
Description
Triplicate 12-Lead ECGs were collected at baseline visit and single ECGs at other timepoints. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.
Time Frame
Baseline, Day 1, Day 4 and Day 8
Title
Change From Baseline in ECG Mean Heart Rate
Description
Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.
Time Frame
Baseline, Day 1 (Pre-dose), Day 4 and Day 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant is greater than equal to (>=)18 years of age at the time of signing the study informed consent.
Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12).
Participant has measurable disease according to RECIST v1.1 criteria.
Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
Participant must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
Participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for NY-ESO-1 expression by a designated central laboratory.
Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Participant has a left ventricular ejection fraction >=45%.
Participant is fit for apheresis and has adequate venous access for the cell collection.
Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.
Exclusion Criteria:
Any previous gene therapy using an integrating vector.
Any previous allogeneic hematopoietic stem cell transplant.
Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
Participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
Participant has known active brain or leptomeningeal metastases.
Participant has other prior malignancy that is not in complete remission.
Participant has uncontrolled intercurrent illness including, but not limited to:
(i) Ongoing or active infection.
(ii) Clinically significant cardiac disease
(iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).
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
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
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
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
http://clinicalstudydatarequest.com
Learn more about this trial
Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
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