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Trial record 3 of 138 for:    NY-ESO-1

A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma (NY-ESO-1)

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ClinicalTrials.gov Identifier: NCT01343043
Recruitment Status : Active, not recruiting
First Posted : April 27, 2011
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE April 26, 2011
First Posted Date  ICMJE April 27, 2011
Last Update Posted Date June 14, 2019
Actual Study Start Date  ICMJE September 27, 2012
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort [ Time Frame: 1 Year ]
    Evaluation of efficacy and duration of response of the treatment by assessment of Best Overall Response Rate according to RECIST v1.1
  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort [ Time Frame: 1 Year ]
    Evaluation of efficacy and duration of response of the treatment by assessment of Overall Survival according to RECIST v1.1
Original Primary Outcome Measures  ICMJE
 (submitted: April 26, 2011)
Determine the response rate. [ Time Frame: Day 28, 60, 100, 180; Month 9, 12, then q6 months x 3 yrs ]
Disease Staging Evaluation: CT scan chest, head, abdomen, pelvis. MRI of tumro, FDG-PET, Bone Scan if indicated.
Change History Complete list of historical versions of study NCT01343043 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [ Time Frame: From date of apheresis up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ]
    Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; and cardiac assessments, including ECG and ECHO/MUGA
  • Evaluation of the persistence of genetically modified T cells [ Time Frame: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ]
    Evaluation of the persistence of the infused T cells in the periphery
  • Percentage of total gene modified T cells with memory subtype [ Time Frame: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ]
    Memory phenotype of genetically modified T cells will be evaluated using flow cytometry.
  • After progressing and after receiving a 2nd dose of NY-ESO-1ᶜ²⁵⁹T, proportion of subjects with a confirmed Complete Response (CR) [ Time Frame: Month 3,6,9, Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2011)
Evaluate persistence and expansion of NY-ESO-1 cells [ Time Frame: Daily Days 0-14, D21, D28, D42, D60, Mo: 3, 4, 5, 6, 9, 12; q6mo for 3 yrs ]
Research Analysis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Official Title  ICMJE A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE Biological: NY-ESO-1(c259)T Cells
Cytoreductive 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.
Study Arms  ICMJE
  • Experimental: Cohort 1 treated with NY-ESO-1 T Cells
    High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine. (COMPLETE)
    Intervention: Biological: NY-ESO-1(c259)T Cells
  • Experimental: Cohort 2 treated with NY-ESO-1 T Cells
    Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine.
    Intervention: Biological: NY-ESO-1(c259)T Cells
  • Experimental: Cohort 3 treated with NY-ESO-1 T Cells
    High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than fludarabine. (COMPLETE)
    Intervention: Biological: NY-ESO-1(c259)T Cells
  • Experimental: Cohort 4 treated with NY-ESO-1 T Cells
    High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen.
    Intervention: Biological: NY-ESO-1(c259)T Cells
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 12, 2019)
45
Original Estimated Enrollment  ICMJE
 (submitted: April 26, 2011)
10
Estimated Study Completion Date  ICMJE April 1, 2020
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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.
    • 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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Canada,   France,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01343043
Other Study ID Numbers  ICMJE 208466
ADP 04511 ( Other Identifier: Adaptimmune Therapeutics )
2015-005594-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP