- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02992743
Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
March 21, 2023 updated by: GlaxoSmithKline
A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
23
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Tampa, Florida, United States, 33612
- GSK Investigational Site
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Michigan
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Ann Arbor, Michigan, United States, 48109
- GSK Investigational Site
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Missouri
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Saint Louis, Missouri, United States, 63110
- GSK Investigational Site
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New York
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New York, New York, United States, 10065
- GSK Investigational Site
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Ohio
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Columbus, Ohio, United States, 43210
- GSK Investigational Site
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Texas
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Houston, Texas, United States, 77030
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: letetresgene autoleucel (GSK3377794)
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.
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Fludarabine will be used as a lymphodepleting chemotherapy.
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
Letetresgene autoleucel (GSK3377794) as an IV infusion.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Response (TTR) Assessed by Investigator
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Time to Response (TTR) Assessed by Independent Reviewer
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Number of Participants With Adverse Event of Special Interest (AESI)
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Number of Participants With Replication Competent Lentivirus (RCL)
Time Frame: Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion
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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).
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Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion
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Number of Participants With Insertional Oncogenesis
Time Frame: Up to 2 years
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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.
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Up to 2 years
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Number of Participants With Positive Anti-drug Antibodies (ADAs)
Time Frame: Up to 24 Months
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Serum samples were collected to analyze for the presence of ADAs using validated immunoassays.
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Up to 24 Months
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Maximum Transgene Expansion (Cmax) of GSK3377794
Time Frame: Day 2 to Day 15
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Cmax was defined as peak cell expansion during the interventional phase.
Blood samples were collected to measure Cmax.
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Day 2 to Day 15
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Time to Cmax (Tmax)
Time Frame: Day 2 to Day 15
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Tmax was defined as time to peak cell expansion during the interventional phase.
Blood samples were collected to measure Tmax.
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Day 2 to Day 15
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Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794
Time Frame: Up to 28 days
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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).
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Up to 28 days
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Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
Time Frame: Baseline, Day 1, Day 4 and Day 8
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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.
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Baseline, Day 1, Day 4 and Day 8
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Change From Baseline in ECG Mean Heart Rate
Time Frame: Baseline, Day 1 (Pre-dose), Day 4 and Day 8
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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.
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Baseline, Day 1 (Pre-dose), Day 4 and Day 8
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Duration of Response (DOR) Assessed by Investigator
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Progression Free Survival (PFS) Assessed by Investigator
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Duration of Response (DOR) Assessed by Independent Reviewer
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Progression Free Survival (PFS) Assessed by Independent Reviewer
Time Frame: Up to 24 months
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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.
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Up to 24 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 6, 2016
Primary Completion (Actual)
November 1, 2021
Study Completion (Actual)
March 22, 2022
Study Registration Dates
First Submitted
December 12, 2016
First Submitted That Met QC Criteria
December 12, 2016
First Posted (Estimate)
December 14, 2016
Study Record Updates
Last Update Posted (Actual)
April 11, 2023
Last Update Submitted That Met QC Criteria
March 21, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Neoplasms, Adipose Tissue
- Liposarcoma
- Liposarcoma, Myxoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
Other Study ID Numbers
- 208469
- ADP-0011-007 (Other Identifier: Adaptimmune Therapeutics)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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 Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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