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Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin

NCT02414269

Description:

The purpose of this Phase I study is to test the safety of different doses of specially prepared immune cells (called "T cells") collected from blood. The Investigators want to find a safe dose of these modified T cells for patients who have malignant pleural disease. They want to find out what effects these T cells have on the patient and the cancer (MPD).

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pleural Mesothelioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the <span class="go-doc-concept go-doc-disease">Cancer</span>-Cell Surface Antigen Mesothelin

Title

  • Brief Title: Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin
  • Official Title: A Phase I Clinical Trial of Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin
  • Clinical Trial IDs

    NCT ID: NCT02414269

    ORG ID: 15-007

    Trial Conditions

    Malignant Pleural Disease

    Mesothelioma

    Metastases

    Lung Cancer

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    cyclophosphamide modified T cells with cyclophosphamide

    Trial Purpose

    The purpose of this Phase I study is to test the safety of different doses of specially
    prepared immune cells (called "T cells") collected from blood. The Investigators want to
    find a safe dose of these modified T cells for patients who have malignant pleural disease.
    They want to find out what effects these T cells have on the patient and the cancer (MPD).

    Detailed Description

    This is an open-label, dose-escalating, non randomized, single-center, phase I study of
    mesothelin-targeted T cells administered intrapleurally as a single infusion in patients
    with a diagnosis (histologically or cytologically documented) of MPD from mesothelioma, lung
    cancer, or breast cancer. The total number of patients studied will depend on the number of
    dose levels tested, up to a maximum dose of 310^6 mesothelin-targeted T cells/kg or until
    the maximum tolerated dose (MTD) is reached.

    Trial Arms

    Name Type Description Interventions
    modified T cells alone (without chemotherapy) Experimental Following enrollment, leukapheresis product will be obtained in the blood donor facility at MSKCC and cryopreserved in the CTCEF. Before protocol treatment, leukapheresis product will be thawed, and T cell isolation, transduction, and expansion of iCasp928z T cells will be performed in the MSKCC Cell Therapy and Cell Engineering Facility. It is estimated that it will take approximately 3 to 6 weeks to generate T cells for treatment.
    modified T cells with cyclophosphamide Experimental Patients will receive cyclophosphamide intravenously (at 1.5 g/m^2) , 2 - 7 (Day (-7) -(-2) days before T cell infusion. On Day 1 , patients will be admitted to the MSKCC Thoracic Surgery Inpatient Service (if not already inpatients) for intravenous hydration, clinical monitoring, and blood work for immune monitoring. Standard MSKCC antiemetic therapy will be administered prior to chemotherapy to prevent nausea/vomiting. Administration of corticosteroids will be avoided as steroids may impede the efficacy of CAR T cells. cyclophosphamide

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with MPD aged 18 years

    - Karnofsky performance status 70%

    - Patients with malignant pleural disease (MPD), pathologically confirmed at MSKCC, and
    defined as one of the following:

    1. Malignant pleural mesothelioma - previously treated with at least one prior
    treatment regimen.

    2. Non-small cell lung cancer metastatic to the pleurapreviously treated with at
    least one prior treatment regimen (chemotherapy or targeted agent) and
    documented progression of disease. Patients with disease outside of the pleura
    will be discussed among study PI and Co-PIs prior to considered eligible for the
    study. Disease outside of the pleura must not require any immediate therapy.

    3. Breast cancer metastatic to the pleura previously treated with at least one
    prior treatment regimen (chemotherapy or targeted agent) and documented
    progression of disease. Patients with disease outside of the pleura will be
    discussed among study PI and Co-PIs prior to considered eligible for the study.
    Disease outside of the pleura must not require any immediate therapy.

    - Expression of mesothelin must be confirmed by meeting one of the following criteria.

    1. Mesothelin expression (>10% of the tumor expressing mesothelin) by
    immunohistochemical (IHC) analysis

    2. Elevated serum SMRP levels (>0.4 nM/L). Patients must have a free flowing
    pleural effusion requiring management by placement of a pleural catheter.
    Patients with a functional pleural catheter already in place are eligible for
    the study, as long as there are no clinical concerns of infection.

    - Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor) or radiotherapy
    must have been completed at least 28 days prior to administration of T-cells.
    Continuation of hormonal therapy (ie for breast cancer) is acceptable. Prior
    immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or
    CTL4-antagonist or similar agent) must have been completed more than 6 months prior
    to the T cell infusion.

    - Any major thoracic (thoracotomy with lung or esophageal resection) or abdominal
    (laparotomy with organ resection) operation must have occurred at least 28 days
    before study enrollment. Patients who have undergone diagnostic VATS or laparoscopy
    can be included in the study.

    - All acute toxic effects of any previous radiotherapy, chemotherapy, or surgical
    procedures must have resolved to grade I or lower according to CTCAE (version 4.0).

    - Lab requirements (hematology)

    - White blood cell (WBC) count 3000 cells/mm3

    - Absolute neutrophil count 1500 neutrophils/mm3

    - Platelet count 100,000 platelets/mm3 Lab requirements (serum chemistry)

    - Bilirubin <1.5x upper limit of normal (ULN)

    - Serum alanine aminotransferase/serum aspartate aminotransferase (ALT/AST) <2.5x ULN

    - Serum creatinine <1.5x ULN or Cr > 1.5x ULN, but calculated clearances of >60

    - Negative screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV)
    antigen, and hepatitis C virus (HCV). If testing was performed during the previous 3
    months, there is no need to repeat testing, as long as documentation of results is
    provided to the study site. Subjects must receive counseling and sign a separate
    informed consent form for HIV testing.

    - Subjects and their partners with reproductive potential must agree to use an
    effective form of contraception during the period of drug administration and for 4
    weeks after completion of the last administration of the study drug. An effective
    form of contraception is defined as oral contraceptives plus 1 form of barrier or
    double-barrier method contraception (condom with spermicide or condom with
    diaphragm).

    - Subjects must be able to understand the potential risks and benefits of the study and
    must be able to read and provide written, informed consent for the study

    Exclusion Criteria:

    - Any prior history of brain metastases

    - Non-small cell lung cancer metastatic to the pleura that extends outside of the
    pleura requiring immediate therapy

    - Breast cancer metastatic to the pleura that extends outside of the pleura requiring
    immediate therapy

    - Prior history of seizure disorder

    - Patients currently receiving treatment for concurrent active malignancy

    - Autoimmune or antibody-mediated disease, including but not limited to systemic lupus
    erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and
    temporal arteritis (Patients with a history of hypothyroidism will not be excluded)

    - Clinically significant cardiac disease (New York Heart Association class III/IV) or
    severe debilitating pulmonary disease

    - Pregnant or lactating women

    - An infection requiring antibiotic treatment within 7 days before the start of
    treatment (day 0)

    - A requirement for daily systemic corticosteroids for any reason or a requirement for
    other immunosuppressive or immunomodulatory agents. Topical, nasal, and inhaled
    steroids are permitted.

    - Administration of live, attenuated vaccine within 8 weeks before the start of
    treatment (day 0) and throughout the study

    - Any other medical condition that, in the opinion of the PI, may interfere with a
    subject's participation in or compliance with the study

    - Participation in a therapeutic research study or receipt of an investigational drug
    within 30 days before the screening visit

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Composite measure of severity and number of adverse events (AEs); changes in clinical laboratory test findings (hematologic and chemistry); and physical examination.

    Secondary Outcome Measures

    Changes in serum levels of the biomarker soluble mesothelin related peptide (SMRP)

    Trial Keywords

    modified T cells

    cyclophosphamide

    CAR T cells

    15-007