A study of NY-ESO-1 T-cells (GSK3377794) in synovial sarcoma and myxoid/round cell liposarcoma patients
- Conditions
- Synovial sarcoma and Myxoid/Round Cell Liposarcoma (MRCLS)MedDRA version: 20.0Level: PTClassification code 10042863Term: Synovial sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10073137Term: Myxoid liposarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000415-87-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
1.Capable of giving signed informed consent including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. For participants <18 years of age (or the legal minimum age in the relevant country) their legal guardian must give informed consent. Pediatric participants will be included in age-appropriate discussion in order to obtain assent.
2.Participant must be =10 years of age at the time of signing the informed consent. Participant scheduled to receive clinical drug product supply must also weigh =40 kg. For participant scheduled to receive commercial drug product supply and weighing <40kg, the Investigator must also consult with the Medical Monitor prior to inclusion.
3.Participant has a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma, confirmed by local histopathology and with evidence of translocation per below:
– for synovial sarcoma, the presence of a translocation between SYT on the X chromosome and SSX1, SSX2 or, SSX4 on chromosome 18 (may be presented in the pathology report as t (X;18)) is required;
– for myxoid/round cell liposarcoma, the presence of a translocation t (12;16)(q13;p11) or the variant translocation t (12;22)(q13;q12) is required.
4.Participant has high-risk locally advanced (i.e. deeply seated, high grade, positive margins, large [=5 cm], or locally recurrent) synovial sarcoma or myxoid/round cell liposarcoma.
5.Participant with synovial sarcoma or myxoid/round cell liposarcoma who is
a)for Substudy 1:Newly diagnosed, previously untreated OR
b)Relapsed after surgery or radiotherapy for localized disease OR
c)Relapsed =1 year after adjuvant/neoadjuvant therapy for localized disease for Substudy 2: Participant is either currently being treated with or has completed at least one standard of care treatment including anthracycline-containing regimens (e.g. doxorubicin alone, doxorubicin with ifosfamide, etc.) for advanced (metastatic or inoperable) disease.
6.Male or female. Contraception requirements will apply at the time of leukapharesis and treatment.
7. A representative tumor tissue specimen (archived or fresh biopsy) with associated pathology report should be available to perform NY-ESO-1 antigen expression analysis, unless a recent NY-ESO-1 expression test result from the same designated central laboratory, following the same procedures, has already been performed under a separate GSK-sponsored protocol or under another substudy. For guidance on acceptable specimen material see Tumor Biopsies under Section 5.1
Leukapheresis Eligibility Screening
All the Inclusion Criteria in 1-7 must apply again prior to leukapheresis. In addition, the following criteria must also apply:
8.Life expectancy =24 weeks
9.Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. Unresectable refers to a tumor lesion in which clear surgical excision margins cannot be obtained without leading to significant functional compromise.
10.Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central lab prior to leukapheresis. NOTE: An HLA test result from the same designated central laboratory, following the same procedures, and performed under a separate GSK-sponsored protocol or under another substudy is acceptable
11.Participant’s tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expres
1.Participant has been previously treated for advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.
2.Central nervous system (CNS) metastases.
3.Any other prior malignancy that is not in complete remission.
Exceptions include:
a.completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma (e.g. melanoma in situ, basal cell carcinoma, prostate cancer in-situ, periosteal osteosarcoma)
b.previous malignancies that have been definitively treated, and have been in remission for 5 years may be enrolled upon consultation with sponsor Medical Monitor or designee
4.Previous treatment with genetically engineered NY-ESO-1 specific T cells.
5.Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
6.Prior gene therapy using an integrating vector.
7.Previous allogeneic hematopoietic stem cell transplant.
8.Clinically significant systemic illness:
a.serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the participant’s ability to tolerate protocol therapy or significantly increase the risk of complications
OR
b.prior or active demyelinating disease
Leukapheresis Eligibility Screening
Participants are not eligible for leukapharesis if any of the Exclusion criteria 1-8 apply. Please note in particular that mandatory washout period restrictions must be respected (Table 5) before starting leukapheresis. In addition, participants are not eligible for leukapharesis if any of the following criteria apply:
9.Participant has history of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn’s disease, systemic lupus) requiring steroids or other immunosuppressive treatments.
10.Uncontrolled intercurrent illness including, but not limited to:
a.Ongoing or active infection
b.Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class 3 /Class 4
c.Uncontrolled clinically significant arrhythmia
d.Acute coronary syndrome (angina or myocardial infarction) in last 6 months
e.Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded; however, participants cannot be oxygen dependent)
11.Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, persistent jaundice or cirrhosis.
12.QTc >480 msec NOTES: The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant and then the lowest QTc value used to include or discontinue the participant from the trial. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
13.Participant has a his
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method