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. 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

5x10⁹/kg with a minimum of 1x10⁹/kg to a maximum of 6x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T.

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-1ᶜ²⁵⁹T.

Cohort 3: Up to 20 patients may be enrolled to achieve at least 10 evaluable patients

treated with NY-ESO-1ᶜ²⁵⁹T.

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. For patients whose cell dose fails to meet

the minimum cell dose requirement of 1x10⁹ transduced cells, those patients will still be

eligible to receive NY-ESO-1ᶜ²⁵⁹T and participate on this protocol, however, an additional

patient whose cell dose meets the minimum requirement of 1x10⁹ transduced cells will be

added to the cohort.

Patients <40 kg will be dosed per body weight with a minimum 0.025x10⁹ transduced

cells/kg, with a target dose of 0.125x10⁹ 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-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 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/mm³

Platelets ≥ 75,000/mm³

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.

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
    Principal Investigator

    Florida
    Tampa

    Moffitt Cancer Center

    Mihaela M. Druta
    Principal Investigator

    Maryland
    Bethesda

    National Institutes of Health Clinical Center

    John W. Glod
    Ph: 301-451-0391
    Email: john.glod@nih.gov

    John W. Glod
    Principal Investigator

    New York
    New York

    Memorial Sloan-Kettering Cancer Center

    Sandra Pierina D'Angelo
    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.