NeoplasmsPhase 1NY-ESO-1NCT01343043
A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
A Phase 1 study testing NY-ESO-1(c259)T Cells, Fludarabine and Cyclophosphamide in people with Neoplasms, run by GlaxoSmithKline at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- NY-ESO-1(c259)T Cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 8 sitesUnited States
- Study dates
- 27 Sep 2012to 18 Jun 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 23Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
GSK Investigational Site
Bethesda, Maryland, 20892
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Duarte, California, 91010
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
New York, New York, 10065
GSK Investigational Site
St Louis, Missouri, 63110
GSK Investigational Site
Tampa, Florida, 33612
About this study
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.
Read the 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.
- Conditions
- Neoplasms
- Being tested
- NY-ESO-1(c259)T Cells, Fludarabine, Cyclophosphamide
- Keywords
- T Cell Receptor, Sarcoma, Cell Therapy, T Cell Therapy, Previously treated, NY-ESO-1, Metastatic, Immuno-oncology
- Medical subject headings
- Neoplasms, Sarcoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NY-ESO-1(c259)T CellsDrug
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.
FludarabineDrug
Fludarabine will be used as lymphodepleting chemotherapy.
CyclophosphamideDrug
Cyclophosphamide will be used as lymphodepleting chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 treated with NY-ESO-1 T Cells | Experimental | High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. Receives: Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide |
| Cohort 2 treated with NY-ESO-1 T Cells | Experimental | Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. Receives: Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide |
| Cohort 3 treated with NY-ESO-1 T Cells | Experimental | High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy. Receives: Drug: NY-ESO-1(c259)T Cells; Drug: Cyclophosphamide |
| Cohort 4 treated with NY-ESO-1 T Cells | Experimental | High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy. Receives: Drug: NY-ESO-1(c259)T Cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 4.5 years
Secondary outcomes (13)
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.
Measured: Up to 4.5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to 5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to 4.5 years
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.
Measured: Up to Week 4
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.
Measured: Up to Week 4
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.
Measured: Up to Week 4
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.
Measured: Up to Week 4
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.
Measured: Up to 4.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2011 (estimated)
- Study start27 Sep 2012
- Primary completion18 Jun 2019
- Study completion18 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01343043
- Sponsor's protocol ID
- 208466
- Other IDs
- ADP 04511, 2015-005594-21, 2015
- Acronym
- NY-ESO-1
- Status last verified
- Jun 2021
- First submitted
- 26 Apr 2011
- Last updated
- 30 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
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.
PubMed 36075914Ramachandran 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.
PubMed 31651363D'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.
PubMed 29891538
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
- ClinicalTrials.gov ID
- NCT01343043
- Acronym / sponsor ID
- NY-ESO-1 / 208466
- Conditions
- Neoplasms
- Keywords
- T Cell Receptor, Sarcoma, Cell Therapy, T Cell Therapy, Previously treated, NY-ESO-1, Metastatic, Immuno-oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 27 Sep 2012 (actual)
- Primary completion
- 18 Jun 2019 (actual)
- Study completion
- 18 Jun 2019 (actual)
- First posted
- 27 Apr 2011 (estimated)
- Results
- Posted 9 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 treated with NY-ESO-1 T Cells | Experimental | Drug: NY-ESO-1(c259)T Cells, Drug: Fludarabine, Drug: CyclophosphamideHigh NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. |
| Cohort 2 treated with NY-ESO-1 T Cells | Experimental | Drug: NY-ESO-1(c259)T Cells, Drug: Fludarabine, Drug: CyclophosphamideLow NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine as the lymphodepleting chemotherapy. |
| Cohort 3 treated with NY-ESO-1 T Cells | Experimental | Drug: NY-ESO-1(c259)T Cells, Drug: CyclophosphamideHigh NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine as the lymphodepleting chemotherapy. |
| Cohort 4 treated with NY-ESO-1 T Cells | Experimental | Drug: NY-ESO-1(c259)T Cells, Drug: Fludarabine, Drug: CyclophosphamideHigh NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen as the lymphodepleting chemotherapy. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (23 listed)
- 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:
- 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
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NY-ESO-1(c259)T CellsLymphodepleting 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. | Drug | 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 |
| FludarabineFludarabine will be used as lymphodepleting chemotherapy. | Drug | Cohort 1 treated with NY-ESO-1 T Cells, Cohort 2 treated with NY-ESO-1 T Cells, Cohort 4 treated with NY-ESO-1 T Cells |
| CyclophosphamideCyclophosphamide will be used as lymphodepleting chemotherapy. | Drug | 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 |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 4.5 years
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.
13 secondary outcomes
Duration of Overall Response
Time frame: Up to 4.5 years
Progression Free Survival
Time frame: Up to 4.5 years
Best Overall Response
Time frame: Up to 4.5 years
Overall Survival
Time frame: Up to 4.5 years
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 5 years
Number of Participants With Worst Post-Baseline Grade Results for Hematology Parameters
Time frame: Up to 4.5 years
Number of Participants With Worst Post-Baseline Grade Results for Clinical Chemistry Parameters
Time frame: Up to 4.5 years
Number of Participants With at Least One Confirmed Positive Post-Baseline Anti-infused (NY-ESO-1 Genetically Engineered T) Cell Antibody Result
Time frame: Up to 4.5 years
Concentration of Cytokines in Cytokine Release Syndrome (CRS) by CRS Status: Cohort 1: High NY-ESO-1 Expression Treated With Regimen A
Time frame: Up to Week 4
Concentration of Cytokines in CRS by CRS Status: Cohort 2: Low NY-ESO-1 Expression Treated With Regimen A
Time frame: Up to Week 4
Concentration of Cytokines in CRS by CRS Status: Cohort 3: High NY-ESO-1 Expression Treated With Regimen B
Time frame: Up to Week 4
Concentration of Cytokines in CRS by CRS Status: Cohort 4: High NY-ESO-1 Expression Treated With Regimen C
Time frame: Up to Week 4
Time to Maximum Persistence of NY-ESO-1 Genetically Engineered T Cells
Time frame: Up to 4.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36075914Gyurdieva 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.
- Derived from this study: PubMed 31651363Ramachandran 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.
- Derived from this study: PubMed 29891538D'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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NY-ESO-1(c259)T Cells, Fludarabine and Cyclophosphamide in people with Neoplasms, run by GlaxoSmithKline at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 4.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01343043, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2021.