T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
Condition: Melanoma; Meningioma; Breast Cancer; Non-Small Cell Lung Cancer; Hepatocellular Cancer
MeSH terms: Melanoma; Meningioma; Liver Neoplasms; Carcinoma, Hepatocellular
Intervention: Anti-NY ESO-1 mTCR PBL; Cyclophosphamide; Fludarabine; Aldesleukin
Intervention description: Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.; Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenously (IV) in 250 mL dextrose 5% in water (D5W) infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.; Days -7 to -3: Fludarabine 25 mg /m^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.; Aldesleukin 720,000 IU/kg intravenously (IV) (based on total body weight) over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 15 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Metastatic Cancer; Gene Therapy; Immunotherapy; Tumor Regression; Melanoma

Summary:

      Background:

      The National Cancer Institute (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 National Institutes of
           Health (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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA - PATIENTS WITH SOLID TUMOR CANCERS AND MELANOMA:

          -  Measurable (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria)
             metastatic cancer or locally advanced refractory/recurrent malignancy including
             melanoma that expresses ESO as assessed by one of the following methods: reverse
             transcription polymerase chain reaction (RT-PCR) on tumor tissue, immunohistochemistry
             of resected tissue, or serum antibody reactive with ESO.

          -  Confirmation of diagnosis of metastatic cancer including melanoma by the National
             Cancer Institute (NCI) Laboratory of Pathology.

          -  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.

          -  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.

          -  More than four weeks must have elapsed since any prior systemic therapy at the time
             the patient receives the preparative regimen, and patient's 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 three weeks, as
        long as all toxicities have recovered to grade 1 or less.

        Note: Patients who have previously received ipilimumab and have documented gastrointestinal
        (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

        INCLUSION CRITERIA - PATIENTS WITH MALIGNANT MENINGIOMA:

        - 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.

          -  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.

          -  At least 4 weeks post-surgery, and must be at least 3 months post-radiation therapy,
             with resolution of related toxicities.

          -  Measurable disease on magnetic resonance imaging (MRI) scan.

          -  No history of intracranial hemorrhage.

          -  Patients with a history of neurofibromatosis (NF) may have other stable central
             nervous system (CNS) tumors, such as schwannoma, acoustic neuroma, or ependymoma only
             if those lesions have been stable for the past 6 months.

          -  Patients must be on stable dose of steroids for at least 5 days prior to baseline
             imaging.

        INCLUSION CRITERIA - ALL PATIENTS:

          -  Age greater than or equal to 15 years and less than or equal to 70 years.

          -  Patient, or their parent(s)/legal guardian(s) (if the patient is < 18 years of age),
             is able to understand and willing to sign a written informed consent. Written assent
             will be obtained for participants under the age of 18 as appropriate.

          -  All participants greater than or equal to 18 years of age must be willing to sign a
             durable power of attorney.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

          -  Patients aged 15-17 years weigh greater than or equal to 50 kg.

          -  Human leukocyte antigen serotype within the HLA-A serotype group (HLA-A*0201)
             positive.

          -  Patients of both genders must be willing to practice birth control from the time of
             enrollment on this study and for four months after treatment.

          -  Women of child-bearing potential must have a negative pregnancy test because of the
             potentially dangerous effects of the treatment on the fetus.

          -  Serology

               -  Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental
                  treatment being evaluated in this protocol depends on an intact immune system.
                  Patients who are HIV seropositive may have decreased immune-competence and thus
                  may 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 Hepatitis C Virus Ribonucleic acid(HCV RNA)
                  negative.

          -  Hematology

               -  Absolute neutrophil count (ANC) greater than 1000/mm(3) without the support of
                  filgrastim

               -  White blood cells (WBC) greater than or equal to 3000/mm(3)

               -  Platelet count greater than or equal to 100,000/mm(3)

               -  Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this
                  cut-off.

          -  Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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.

          -  Subjects must be co-enrolled in protocol 03-C-0277.

        EXCLUSION CRITERIA:

          -  Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the treatment on the fetus or infant.

          -  Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
             Disease).

          -  Active systemic infections requiring anti-infective treatment, coagulation disorders,
             or any other active or uncompensated major medical illnesses.

          -  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).

          -  Concurrent systemic steroid therapy.

          -  History of severe immediate hypersensitivity reaction to cyclophosphamide,
             fludarabine, or aldesleukin.

          -  History of coronary revascularization or ischemic symptoms.

          -  Documented Left Ventricular Ejection Fraction (LVEF) less than or equal to 45% tested
             in patients:

               -  Age greater than or equal to 65 years

               -  With clinically significant atrial and/or ventricular arrhythmias, including but
                  not limited to: atrial fibrillation, ventricular tachycardia, second- or
                  third-degree heart block or have a history of ischemic heart disease and/or chest
                  pain.

          -  Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted
             tested in patients with:

               -  A prolonged history of cigarette smoking (greater than or equal to 20 pack-year
                  smoking history, with cessation within the past two years).

               -  Symptoms of respiratory dysfunction.

          -  Patients who are receiving any other investigational agents.