Last updated: 04/15/2021 12:10:07
A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients with Synovial SarcomaNY-ESO-1
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients with Synovial Sarcoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Not applicable
Allocation:
Non-randomized
Primary outcomes:
Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort
Timeframe: 1 Year
Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort
Timeframe: 1 Year
Secondary outcomes:
Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)
Timeframe: From date of apheresis up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years
Evaluation of the persistence of genetically modified T cells
Timeframe: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years
Percentage of total gene modified T cells with memory subtype
Timeframe: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years
After progressing and after receiving a 2nd dose of NY-ESO-1ᶜ²⁵⁹T, proportion of subjects with a confirmed Complete Response (CR)
Timeframe: Month 3,6,9, Year 1, Every 3 months until 2 years, then Every 6 months until 5 years
Interventions:
Drug: NY-ESO-1(c259)T Cells
Drug: Fludarabine
Drug: Cyclophosphamide
Enrollment:
50
Observational study model:
Not applicable
Primary completion date:
2019-18-06
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms
Product
GSK3377794, cyclophosphamide, fludarabine
Collaborators
Not applicable
Study date(s)
September 2012 to June 2019
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
4 years - 0 Not applicable
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
- Measurable disease
- Cohort 1 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
- Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
- HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 by high resolution testing at a local or central laboratory
- Weigh more than 18 kg
- All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
- Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
- Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
- Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion lymphodepletive chemotherapy.
- ECOG 0-1, or for children ≤10 years of age, Lansky > 60
- Life expectancy > 3 months
- Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
- T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome total bilirubin <3xULN and direct bilirubin ≤ 35%)
- AST, ALT ≤ 2.5 x upper limit of normal
- ANC ≥ 1.0 x 10⁹/L
- Platelets ≥ 75 x 10⁹/L
- Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
- Ability to give informed consent for patients greater than 18 years of age. For patients less than 18 years of age the legal guardian must give informed consent.
- Male patients must be willing to practice birth control (including abstinence) during and for 4 months after treatment. Female patients must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.
Patients must have proven positive tumor sample for NY-ESO-1 as follows:
Exclusion criteria:
- Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody.
Trial location(s)
Location
GSK Investigational Site
Bethesda, Maryland, United States, 20892
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2019-18-06
Actual study completion date
2019-18-06
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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