Clinical Trials /

Gene-Modified T Cells, Vaccine Therapy, and Nivolumab in Treating Patients With Stage IV or Locally Advanced Solid Tumors Expressing NY-ESO-1

NCT02775292

Description:

This phase I trial studies the side effects and the best dose of nivolumab when given together with gene-modified T cells and vaccine therapy in treating patients with solid tumors that express the cancer-testes antigen NY-ESO-1 gene AND have spread from where it started to nearby tissue or lymph nodes (locally advanced) or distant organs (stage IV). T cells are a special type of white blood cells (immune cell) that have the ability to kill cancer cells. Nivolumab may block PD-1 which is found on T cells and help the immune system kill cancer cells. Placing a modified gene for the NY-ESO-1 T cell receptor (TCR) into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Dendritic cells are another type of blood cell that can teach other cells in the body to look for cancer cells and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help dendritic cells teach the immune system to target cancer cells expressing that protein, and further help the T cells attack cancer. Giving nivolumab together with gene-modified T-cells and dendritic cell vaccine may teach the immune system to recognize and kill cancer cells that express NY-ESO-1.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Gene-Modified T Cells, Vaccine Therapy, and <span class="go-doc-concept go-doc-intervention">Nivolumab</span> in Treating Patients With Stage IV or Locally Advanced Solid Tumors <span class="go-doc-concept go-doc-keyword">Expressing</span> <span class="go-doc-concept go-doc-alteration">NY-ESO-1</span>

Title

  • Brief Title: Gene-Modified T Cells, Vaccine Therapy, and Nivolumab in Treating Patients With Stage IV or Locally Advanced Solid Tumors Expressing NY-ESO-1
  • Official Title: NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With Nivolumab PD-1 Blockade
  • Clinical Trial IDs

    NCT ID: NCT02775292

    ORG ID: 15-001433

    NCI ID: NCI-2016-00201

    Trial Conditions

    Adult Solid Neoplasm

    Childhood Solid Neoplasm

    Metastatic Neoplasm

    Trial Interventions

    Drug Synonyms Arms
    Cyclophosphamide (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719 Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)
    Fludarabine Phosphate 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Oforta, SH T 586 Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab)

    Trial Purpose

    This phase I trial studies the side effects and the best dose of nivolumab when given
    together with gene-modified T cells and vaccine therapy in treating patients with solid
    tumors that express the cancer-testes antigen NY-ESO-1 gene AND have spread from where it
    started to nearby tissue or lymph nodes (locally advanced) or distant organs (stage IV). T
    cells are a special type of white blood cells (immune cell) that have the ability to kill
    cancer cells. Nivolumab may block PD-1 which is found on T cells and help the immune system
    kill cancer cells. Placing a modified gene for the NY-ESO-1 T cell receptor (TCR) into the
    patients' T cells in the laboratory and then giving them back to the patient may help the
    body build an immune response to kill tumor cells that express NY-ESO-1. Dendritic cells are
    another type of blood cell that can teach other cells in the body to look for cancer cells
    and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help
    dendritic cells teach the immune system to target cancer cells expressing that protein, and
    further help the T cells attack cancer. Giving nivolumab together with gene-modified T-cells
    and dendritic cell vaccine may teach the immune system to recognize and kill cancer cells
    that express NY-ESO-1.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the safety of the addition of the PD-1 blocking monoclonal antibody,
    nivolumab, to NY-ESO TCR-transduced autologous peripheral blood lymphocyte (PBL) adoptive
    cell transfer (ACT) in a dose escalation scheme in two study cohorts at 1 mg/kg and 3 mg/kg
    of nivolumab intravenous (i.v.) every two weeks for up to 2 years.

    SECONDARY OBJECTIVES:

    I. To determine the feasibility of delivering the TCR transgenic cell dose and PD-1 blockade
    to patients.

    II. To determine the persistence of NY-ESO-1 TCR-engineered peripheral blood mononuclear
    cell (PBMC) in serial peripheral blood samples and in biopsies of accessible metastatic
    lesions.

    EXPLORATORY OBJECTIVES:

    I. To determine whether blocking PD-1 will maintain the antitumor functionality of
    adoptively transferred TCR transgenic lymphocytes.

    II. To explore the use of positron emission tomography (PET)-based imaging using the PET
    tracer (18F) fluorodeoxy-glucose ([18F]FDG) with the goal of determining if the adoptively
    transferred NY-ESO-1 TCR-engineered PBMC when administered with nivolumab home and expand in
    secondary lymphoid organs and tumor deposits.

    III. Clinical antitumor activity recording objective response rate.

    OUTLINE: This is a dose-escalation study of nivolumab.

    CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on
    days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1.

    NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 TCR PBMC IV on day 0.

    NIVOLUMAB: Patients receive nivolumab IV over 60 minutes on day 0 or 1. Treatment repeats
    every 2 weeks for up to 2 years in the absence of disease progression or unacceptable
    toxicity.

    NY-ESO-1(157-165) PEPTIDE PULSED DENDRITIC CELL (DC): Patients receive NY-ESO-1(157-165)
    peptide pulsed DC intradermally (ID) on days 1, 14, and 28.

    LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin subcutaneously (SC) twice
    daily (BID) for 7 days beginning on day 1 for a maximum of 14 doses.

    After completion of study treatment, patients are followed up at least every 6 months for 3
    years and then at least every 12 months for up to 15 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (NY-ESO-1 TCR transduced PBMC, vaccine, nivolumab) Experimental CONDITIONING REGIMEN: Patients receive cyclophosphamide IV over 1 hour on days -5 to -4 and fludarabine phosphate IV over 30 minutes on days -4 to -1. NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 TCR PBMC IV on day 0. NIVOLUMAB: Patients receive nivolumab IV over 60 minutes on day 0 or 1. Treatment repeats every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. NY-ESO-1(157-165) PEPTIDE PULSED DC: Patients receive NY-ESO-1(157-165) peptide pulsed DC ID on days 1, 14, and 28. LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin SC BID for 7 days beginning on day 1 for a maximum of 14 doses. Cyclophosphamide, Fludarabine Phosphate

    Eligibility Criteria

    Inclusion Criteria:

    - Stage IV or locally advanced histologically confirmed solid tumors for which no
    alternative therapies with proven survival advantage are available

    - At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or
    palpable metastatic site or a deeper site accessible by image-guided biopsy that is
    deemed safe to access by the treating physicians and interventional radiologists;
    patients without accessible lesions for biopsy but with prior tissue available from
    metastatic disease would be eligible at the investigator's discretion

    - NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly
    available NY-ESO-1 antibodies

    - Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping

    - Age greater than or equal to 16 years old

    - A minimum of one measurable lesion defined as:

    - Meeting the criteria for measurable disease according to Response Evaluation
    Criteria In Solid Tumors (RECIST)

    - Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be
    accurately measured and recorded by color photography with a ruler to document
    the size of the target lesion(s)

    - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

    - Absolute neutrophil count >= 1.5 x 10^9 cells/L

    - Platelets >= 100 x 10^9/L

    - Hemoglobin >= 9 g/dL

    - Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal
    (ULN) (=< 5 x ULN, if documented liver metastases are present)

    - Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome)

    - Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)

    - Must be willing and able to accept two leukapheresis procedures

    - Must be willing and able to provide written informed consent

    Exclusion Criteria:

    - Previously known hypersensitivity to any of the agents used in this study

    - Received systemic treatment for cancer, including immunotherapy, within one month
    prior to initiation of dosing within this protocol

    - History of, or significant evidence of risk for, chronic inflammatory or autoimmune
    disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's
    thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic
    lupus erythematosus, hypophysitis, pituitary disorders, etc.); patients will be
    eligible if prior autoimmune disease is not deemed to be active (e.x. fibrotic damage
    of the thyroid after thyroiditis or its treatment, with stable thyroid hormone
    replacement therapy); vitiligo will not be a basis for exclusion

    - History of inflammatory bowel disease, celiac disease, or other chronic
    gastrointestinal conditions associated with diarrhea or bleeding, or current acute
    colitis of any origin

    - Potential requirement for systemic corticosteroids or concurrent immunosuppressive
    drugs based on prior history or received systemic steroids within the last 2 weeks
    prior to enrollment (inhaled or topical steroids at standard doses are allowed)

    - Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired
    immune deficiency state; if there is a positive result in the infectious disease
    testing that was not previously known, the patient will be referred to their primary
    physician and/or infectious disease specialist

    - Hepatitis B or C seropositivity with evidence of ongoing liver damage; if there is a
    positive result in the infectious disease testing that was not previously known, the
    patient will be referred to their primary physician and/or infectious disease
    specialist

    - Dementia or significantly altered mental status that would prohibit the understanding
    or rendering of informed consent and compliance with the requirements of this
    protocol

    - Known clinically active brain metastases; prior evidence of brain metastasis
    successfully treated with surgery or radiation therapy will not be exclusion for
    participation as long as they are deemed under control at the time of study
    enrollment and there are no neurological signs of potential brain metastases

    - Pregnancy or breast-feeding; female patients must be surgically sterile or be
    postmenopausal for two years, or must agree to use effective contraception during the
    period of treatment and 6 months after; all female patients with reproductive
    potential must have a negative pregnancy test (serum/urine) within 24 hours from
    starting the conditioning chemotherapy; the definition of effective contraception
    will be based on the judgment of the study investigators; patients who are
    breastfeeding are not allowed on study

    - Since IL-2 is administered following cell infusion:

    - Patients will be excluded if they have a history of clinically significant
    electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or
    arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a
    cardiac stress test (stress thallium, stress multi gated acquisition scan
    [MUGA], dobutamine echocardiogram, or other stress test)

    - Similarly, patients who are >= 50 years old with a baseline LVEF < 45% will be
    excluded

    - Patients with ECG results of any conduction delays (PR interval > 200 ms,
    corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate <
    50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will
    be evaluated by a cardiologist prior to starting the trial; patients with any
    arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy
    (defined as > 20 premature ventricular contractions [PVCs] per minute),
    ventricular tachycardia, third (3rd) degree heart block will be excluded from
    the study unless cleared by a cardiologist

    - Patients with pulmonary function test abnormalities as evidenced by a forced
    expiration volume in one second (FEV1)/forced vital capacity (FVC) < 70% of
    predicted for normality will be excluded

    - Evidence of diverticulitis at baseline, including evidence limited to computed
    tomography (CT) scan only

    - Received 3 or more prior myelotoxic treatment regimens

    - Bone marrow involvement based on CT or PET scan at screening

    Minimum Eligible Age: 16 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of adverse events, defined following the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Maximum tolerated dose based on dose-limiting toxicity using the Common Toxicity Criteria

    Secondary Outcome Measures

    Feasibility of generating NY-ESO-1 TCR cells and/or NY-ESO 1(157-165) peptide pulsed DC vaccine, determined by the incidence of preparation not meeting the lot release criteria

    Transgenic cell persistence

    Trial Keywords