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

NCT01343043

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.

Related Conditions:
  • Synovial Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

A Pilot Study of Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients With Synovial <span class="go-doc-concept go-doc-disease">Sarcoma</span>

Title

  • Brief Title: A Pilot Study of Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients With Synovial Sarcoma
  • Official Title: A Pilot Study of Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients With Synovial Sarcoma
  • Clinical Trial IDs

    NCT ID: NCT01343043

    ORG ID: ADP 04511

    Trial Conditions

    Synovial Sarcoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    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. Fresh PBMC will be shipped
    to a central manufacturer for gene transduction, activation and expansion, then
    cryopreserved and shipped back to the enrolling institution.

    - Patients will undergo lymphodepletion with cyclophosphamide on Days -3 and -2 with or
    without fludarabine on Days -5 to -2. On Day 0, patients will receive a target dose of
    5x10/kg with a minimum of 1x10/kg to a maximum of 6x10 transduced NY-ESO-1T.

    - The trial seeks to enroll up to 60 patients, that is up to 20 patients per cohort.

    - Cohort 1: Complete

    - Cohort 2: Up to 20 patients may be enrolled to achieve at least 10 evaluable patients
    treated with NY-ESO-1T.

    - Cohort 3: Up to 20 patients may be enrolled to achieve at least 10 evaluable patients
    treated with NY-ESO-1T.

    Patients 40 kg will receive the minimum cell dose of at least 1x10 transduced
    NY-ESO-1T cells with a maximum of 6x10 transduced cells. The target dose for this
    protocol is 5x10 transduced NY-ESO-1T cells. For patients whose cell dose fails to meet
    the minimum cell dose requirement of 1x10 transduced cells, those patients will still be
    eligible to receive NY-ESO-1T and participate on this protocol, however, an additional
    patient whose cell dose meets the minimum requirement of 1x10 transduced cells will be
    added to the cohort.

    - Patients <40 kg will be dosed per body weight with a minimum 0.025x10 transduced
    cells/kg, with a target dose of 0.125x10 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 cycle of treatment, provided eligibility criteria are met.
    The 2nd cycle of treatment will be administered in the same manner as the first
    treatment. Patients who meet the eligibility criteria may receive a 2nd treatment of
    NY-ESO-1T no sooner than 60 days and no later than 2 years following completion of
    the first treatment.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 treated with NY-ESO-1 T Cells Experimental High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine.
    Cohort 2 treated with NY-ESO-1 T Cells Experimental Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine.
    Cohort 3 treated with NY-ESO-1 T Cells Experimental High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than cyclophosphamide.

    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 least 50% of cells that are 2+
    and/or 3+ by immunohistochemistry.

    - Cohort 2 -Positive expression is defined as 1% of cells that are 1+ by
    immunohistochemistry, but not to exceed 50% of cells that are 2+ and/or 3+ by
    immunohistochemistry.

    - Cohort 3 -Positive expression is defined as at least 50% of cells that are 2+
    and/or 3+ by immunohistochemistry.

    - HLA-A*0201, HLA-A*0205, and/or HLA-A*0206 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 completed at least 3 weeks prior
    to study entry.

    - 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 chemo

    - ECOG 0-1, or for children 10 years of age, Lansky 60

    - Life expectancy greater than 3 months

    - Left ventricular ejection fraction 40% or fractional shortening 28%

    - T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome exempt)

    - AST, ALT 2.5 x upper limit of normal

    - ANC > 750/mm

    - Platelets 75,000/mm

    - Age-adjusted normal serum creatinine or a creatinine clearance 60 ml/min/1.73 m2

    - 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 2 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:

    - Clinically significant systemic illness that in the judgment of the PI would
    compromise the patient's ability to tolerate protocol therapy or significantly
    increase the risk of complications.

    - Untreated CNS metastasis

    - Previous treatment with genetically engineered NY-ESO-1 specific T cells. Previous
    vaccine therapy is not an exclusion criteria.

    - Lactating or pregnant females

    - Active HIV, HBV, HCV or HTLV 1/2 infection infection (due to increased risk of
    complications during the preparative 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 with or without elevated liver
    transaminases.

    - Patients who require systemic corticosteroid or other immunosuppressive therapy.
    Immunosuppressive therapy must be stopped at least 14 days prior to cell infusion.

    Minimum Eligible Age: 4 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort

    Secondary Outcome Measures

    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-1T, proportion of subjects with a confirmed Complete Response (CR)

    Trial Keywords

    Sarcoma