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

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase II, Phase ITreatmentActive4 to 55ADP 04511
NCI-2015-00410, NCI-2013-01481, UPCC 04511, NCT01343043

Trial Description

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.

Further Study Information

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.

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.

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Adaptimmune Limited

    Trial Sites

    U.S.A.

    California
    Duarte

    City of Hope Comprehensive Cancer Center

    Warren Allen Chow
    Ph: 800-826-4673
    Email: wchow@coh.org

    Warren Allen Chow
    Principal Investigator

    Florida
    Tampa

    Moffitt Cancer Center

    Mihaela M. Druta
    Ph: 813-745-3242
    Email: mihaela.druta@moffitt.org

    Mihaela M. Druta
    Principal Investigator

    Maryland
    Bethesda

    National Institutes of Health Clinical Center

    John W. Glod
    Ph: 301-402-5940
    Email: john.glod@nih.gov

    John W. Glod
    Principal Investigator

    Massachusetts
    Boston

    Brigham and Women's Hospital

    George Daniel Demetri
    Principal Investigator

    Dana-Farber Cancer Institute

    George Daniel Demetri
    Principal Investigator

    Missouri
    Saint Louis

    Siteman Cancer Center at Washington University

    Brian Andrew Van Tine
    Principal Investigator

    New York
    New York

    Memorial Sloan-Kettering Cancer Center

    Sandra Pierina D'Angelo
    Ph: 646-888-4159
    Email: dangelos@mskcc.org

    Sandra Pierina D'Angelo
    Principal Investigator

    Texas
    Houston

    M D Anderson Cancer Center

    Dejka M. (Steinert) Araujo
    Ph: 713-794-4274
    Email: asreckew@mdanderson.org

    Dejka M. (Steinert) Araujo
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01343043

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.