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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 Summary:

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-1ᶜ²
Sponsor: Adaptimmune

Current Primary Outcome:

  • 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: 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.


Current Secondary Outcome:

  • 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: 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


Information By: Adaptimmune

Dates:
Date Received: April 26, 2011
Date Started: March 2011
Date Completion: March 2028
Last Updated: May 12, 2017
Last Verified: May 2017