Clinical Trials /

T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer

NCT01967823

Description:

Background: The NCI Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying them, and then giving the cells back to the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of the patients who received this treatment experienced shrinking of their tumors. In this study, we are using a slightly different method of producing the anti-ESO-1 cells which we hope will be better in making the tumors shrink. Objectives: The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to shrink and to see if this treatment is safe. Eligibility: - Patients 15 years old and older with cancer that has the ESO-1 molecule on their tumors. Design: - Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed - Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti ESO-1 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.} - Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-ESO-1 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. - Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Related Conditions:
  • Malignant Solid Tumor
  • Meningioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

T Cell Receptor <span class="go-doc-concept go-doc-intervention">Immunotherapy</span> Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer

Title

  • Brief Title: T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
  • Official Title: Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 Murine TCR-Gene Engineered Lymphocytes
  • Clinical Trial IDs

    NCT ID: NCT01967823

    ORG ID: 130214

    NCI ID: 13-C-0214

    Trial Conditions

    Metastatic Cancers Other Than Melanoma That Express ESO Antigen

    Trial Interventions

    Drug Synonyms Arms
    Cyclophosphamide Single Arm
    Fludarabine Single Arm

    Trial Purpose

    Background:

    The NCI Surgery Branch has developed an experimental therapy for treating patients with
    cancer that involves taking white blood cells from the patient, growing them in the
    laboratory in large numbers, genetically modifying them, and then giving the cells back to
    the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type
    of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of
    the patients who received this treatment experienced shrinking of their tumors. In this
    study, we are using a slightly different method of producing the anti-ESO-1 cells which we
    hope will be better in making the tumors shrink.

    Objectives:

    The purpose of this study is to see if these tumor fighting cells (genetically modified
    cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to
    shrink and to see if this treatment is safe.

    Eligibility:

    - Adults 18 years old and older with cancer that has the ESO-1 molecule on their tumors.

    Design:

    - Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and
    undergo a history and physical examination, scans, x-rays, lab tests, and other tests
    as needed

    - Leukapheresis: If the patients meet all of the requirements for the study they will
    undergo leukapheresis to obtain white blood cells to make the anti ESO-1 cells.
    {Leukapheresis is a common procedure which removes only the white blood cells from the
    patient.}

    - Treatment: Once their cells have grown the patients will be admitted to the hospital
    for the conditioning chemotherapy, the anti-ESO-1 cells and aldesleukin. They will stay
    in the hospital for about 4 weeks for the treatment.

    - Follow up: Patients will return to the clinic for a physical exam, review of side
    effects, lab tests, and scans about every 1-3 months for the first year, and then every
    6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2
    days.

    Detailed Description

    PRECIS

    Background:

    - We have constructed a single retroviral vector that contains both and <= chains of a
    murine T cell receptor (mTCR) that recognizes the NY-ESO-1 (ESO) tumor antigen, which
    can be used to mediate genetic transfer of this TCR with high efficiency.

    - In co-cultures with HLA-A2 and ESO double positive tumors, anti-ESO mTCR transduced T
    cells secreted significant amounts of IFN- >= with high specificity.

    Objectives:

    Primary objectives:

    - To determine whether the administration of anti-ESO mTCR-engineered peripheral blood
    lymphocytes (PBL) plus high-dose aldesleukin following a non-myeloablative lymphoid
    depleting preparative regimen may result in objective tumor regression in patients with
    metastatic cancers that express the ESO antigen.

    Secondary objectives:

    - Determine the in vivo survival of mTCR gene-engineered cells.

    - Determine the toxicity profile of this treatment regimen.

    Eligibility:

    Patients who are HLA-A*0201 positive and 18 years of age or older must have

    - Metastatic cancer other than melanoma whose tumors express the ESO antigen;

    - Patients must have previously received and have been a non-responder to or recurred
    after receiving standard care for metastatic disease;

    Patients may not have:

    - Contraindications for high dose aldesleukin administration.

    Design:

    - PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and
    aldesleukin in order to stimulate T-cell growth.

    - Transduction is initiated by exposure of cells to retroviral vector supernatant
    containing the anti- ESO mTCR genes. This mTCR targets the exact same epitope as the
    hTCR.

    - All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
    of cyclophosphamide and fludarabine.

    - On day 0 patients will receive anti-ESO mTCR gene-transduced PBMC and then begin high
    dose aldesleukin.

    - A complete evaluation of evaluable lesions will be conducted 6 weeks (+/- 2 weeks)
    following the administration of the cell product.

    - The study will be conducted using a phase II optimal design (Simon R, Controlled
    Clinical Trials 10:1-10, 1989). The objective will be to determine if the combination
    of high dose aldesleukin, lymphocyte depleting chemotherapy, and anti-ESO TCR-gene
    engineered lymphocytes is able to be associated with a clinical response rate that can
    rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).

    - A total of up to 43 patients may be enrolled (41, plus allowing for up to 2
    non-evaluable patients).

    Trial Arms

    Name Type Description Interventions
    Single Arm Experimental Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by anti-NY ESO-1 mTCR PBL and high dose aldesleukin Cyclophosphamide, Fludarabine

    Eligibility Criteria

    - INCLUSION CRITERIA

    PATIENTS WITH SOLID TUMOR CANCERS

    1. Measurable metastatic cancer or locally advanced refractory/recurrent malignancy
    other than melanoma that expresses ESO as assessed by one of the following methods:
    RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue, or serum
    antibody reactive with ESO.

    2. Confirmation of diagnosis of metastatic cancer by the Laboratory of Pathology of the
    NCI.

    3. Patients must have previously received first line standard therapy (or effective
    salvage chemotherapy regimens) for metastatic disease, if known to be effective for
    that disease, and have been either non-responders (progressive disease) or have
    recurred.

    4. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and
    asymptomatic are eligible. Lesions that have been treated with stereotactic
    radiosurgery must be clinically stable for 1 month after treatment for the patient to
    be eligible. Patients with surgically resected brain metastases are eligible.

    5. More than four weeks must have elapsed since any prior systemic therapy at the time
    the patient receives the preparative regimen, and patients toxicities must have
    recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

    Note: Patients may have undergone minor surgical procedures within the past 3 weeks,
    as long as all toxicities have recovered to grade 1 or less or as specified in the
    eligibility criteria.

    6. Six weeks must have elapsed from the time of any antibody therapy that could affect
    an anti cancer immune response, including anti-CTLA 4 therapy, at the time the
    patient receives the preparative regimen to allow antibody levels to decline.

    Note: Patients who have previously received ipilimumab and have documented GI toxicity
    must have a normal colonoscopy with normal colonic biopsies.

    INCLUSION CRITERIA

    PATIENTS WITH MALIGNANT MENINGIOMA

    1. Histologically proven recurrent meningioma or aggressive meningioma

    Note: Confirmation of ESO expression and pathology is not required in patients with
    definitive radiologic evidence of meningioma who are unresectable, and in whom
    radiation therapy without biopsy is the standard treatment

    2. Recurrent disease/progression after receiving all standard treatments, which must
    include the following:

    - surgical resection, if possible;

    - definitive radiation therapy for unresectable meningioma, or for recurrent
    meningioma after resection

    3. At least 4 weeks post-surgery, and must be at least 3 months post-radiation therapy,
    with resolution of related toxicities

    4. Measurable disease on MRI scan

    5. No history of intracranial hemorrhage

    6. Patients with a history of NF may have other stable CNS tumors, such as schwannoma,
    acoustic neuroma, or ependymoma only if those lesions have been stable for the past 6
    months

    7. Patients must be on stable dose of steroids for at least 5 days prior to baseline
    imaging

    INCLUSION CRITERIA ALL PATIENTS

    1. Greater than or equal to 18 years of age and less than or equal to 70 years of age.

    2. Willing to sign a durable power of attorney

    3. Able to understand and sign the Informed Consent Document

    4. Clinical performance status of ECOG 0 or 1

    5. Life expectancy of greater than three months

    6. Patients must be HLA-A*0201 positive

    7. Patients of both genders must be willing to practice birth control from the time of
    enrollment on this study and for up to four months after treatment

    8. Serology:

    - Seronegative for HIV antibody. (The experimental treatment being evaluated in
    this protocol depends on an intact immune system. Patients who are HIV
    seropositive can have decreased immune-competence and thus be less responsive to
    the experimental treatment and more susceptible to its toxicities.)

    - Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody.
    If hepatitis C antibody test is positive, then patient must be tested for the
    presence of antigen by RT-PCR and be HCV RNA negative.

    9. Women of child-bearing potential must have a negative pregnancy test because of the
    potentially dangerous effects of the treatment on the fetus.

    10. Hematology

    - Absolute neutrophil count greater than 1000/mm(3) without the support of
    filgrastim

    - WBC greater than or equal to 3000/mm(3)

    - Platelet count greater than or equal to 100,000/mm(3)

    - Hemoglobin > 8.0 g/dl

    11. Chemistry:

    - Serum ALT/AST less than or equal to 2.5 times the upper limit of normal

    - Serum creatinine less than or equal to 1.6 mg/dl

    - Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert
    s Syndrome who must have a total bilirubin less than 3.0 mg/dl.

    EXCLUSION CRITERIA

    1. Women of child-bearing potential who are pregnant or breastfeeding because of the
    potentially dangerous effects of the treatment on the fetus or infant.

    2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
    Disease).

    3. Active systemic infections, coagulation disorders or other major medical illnesses of
    the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
    arrhythmias, obstructive or restrictive pulmonary disease.

    4. Concurrent opportunistic infections (The experimental treatment being evaluated in
    this protocol depends on an intact immune system. Patients who have decreased immune
    competence may be less responsive to the experimental treatment and more susceptible
    to its toxicities).

    5. Concurrent systemic steroid therapy.

    6. History of severe immediate hypersensitivity reaction to any of the agents used in
    this study.

    7. History of coronary revascularization or ischemic symptoms

    8. Documented LVEF of less than or equal to 45%. Testing is required in patients with:

    - Clinically significant atrial and/or ventricular arrhythmias including but not
    limited to: atrial fibrillation, ventricular tachycardia, second or third degree
    heart block

    - Age greater than or equal to 60 years old

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Determine whether objective tumor regression can be mediated in patients with metastatic cancers whose tumors express the NY-ESO-1 Antigen who aer treated with anti-NY ESO-1 Antigen who are treated with anti-NY ESO-1 transduced mTCR PBL

    Secondary Outcome Measures

    Trial Keywords

    Metastatic Cancer

    Gene Therapy

    Immunotherapy

    Tumor Regression