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

Titre officiel

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

Sommaire:

Cet essai clinique préliminaire (pilote) a pour but d’évaluer les effets (favorables et défavorables) de la chimiothérapie et de l’immunothérapie par transfert adoptif de lymphocytes T produits par génie génétique pour reconnaître le peptide NY-ESO-1 chez des patients atteints d’un sarcome synovial métastatique ou récurrent non résécable.

Description de l'essai

Primary Outcome:

  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort
  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort
Secondary Outcome:
  • Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)
  • Evaluation of the persistence of genetically modified T cells
  • Percentage of total gene modified T cells with memory subtype
  • After progressing and after receiving a 2nd dose of NY-ESO-1ᶜ²⁵⁹T, proportion of subjects with a confirmed Complete Response (CR)
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, antitumour 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.

Voir cet essai sur ClinicalTrials.gov

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