A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma
Condition: Neoplasms
MeSH terms: Sarcoma; Sarcoma, Synovial
Intervention: NY-ESO-1(c259)T Cells; Fludarabine; Cyclophosphamide
Intervention description: Lymphodepleting 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.; Fludarabine will be used as lymphodepleting chemotherapy.; Cyclophosphamide will be used as lymphodepleting chemotherapy.
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Enrollment: 50.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: T Cell Receptor; Sarcoma; Cell Therapy; T Cell Therapy; Previously treated; NY-ESO-1; Metastatic; Immuno-oncology

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.
    

Eligibility 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

          -  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.