T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Melanoma
Condition: Metastatic Cancer; Metastatic Melanoma
MeSH terms: Melanoma; Neoplasm Metastasis
Intervention: Anti-NY ESO-1 T cell receptor (TCR) cluster of differentiation 62L (CD62L)+ cells; Aldesleukin; Cyclophosphamide; Fludarabine
Intervention description: Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T cell receptor (TCR) CD62L+ cells and high dose aldesleukin.
On day 0, cells (1x10e9 to 2x10e11) will be infused intravenously on the Patient Care Unit over 20-30 minutes.; Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).; On days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.; On days -5 to -1: Fludarabine 25 mg/m(2)/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
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: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Malignant Melanoma; Metastatic Cancer; Gene Therapy; Immunotherapy; Tumor Regression

Summary:

      Background:

      The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for
      treating patients with melanoma 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 selected for a specific cell type, 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 melanoma
      tumors to shrink and to see if this treatment is safe.

      Eligibility:

      -Adults 18 and older with cancer that has the ESO-1 molecule on tumor surfaces

      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:

          1. Measurable metastatic melanoma that expresses ESO as assessed by one of the following
             methods: reverse transcription-polymerase chain reaction (RT-PCR) on tumor tissue, or
             by immunohistochemistry of resected tissue, or serum antibody reactive with ESO.

          2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of the
             National Cancer Institute (NCI).

          3. 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.

          4. Greater than or equal to 18 years of age and less than or equal to 70 years of age.

          5. Willing to sign a durable power of attorney

          6. Able to understand and sign the Informed Consent Document

          7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1

          8. Life expectancy of greater than three months

          9. Patients must be human leukocyte antigen (HLA)-A*0201 positive

         10. 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

         11. 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 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 hepatitis C virus (HCV) ribonucleic acid
                  (RNA) negative.

         12. Women of child-bearing potential must have a negative pregnancy test because of the
             potentially dangerous effects of the treatment on the fetus.

         13. Hematology

               -  Absolute neutrophil count greater than 1000/mm(3) without the support of
                  filgrastim

               -  White blood cell (WBC) greater than or equal to 3000/mm(3)

               -  Platelet count greater than or equal 100,000/mm(3)

               -  Hemoglobin > 8.0 g/dl

         14. 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 Gilberts
                  Syndrome who must have a total bilirubin less than 3.0 mg/dl.

         15. 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 in Section 2.1.

         16. Six weeks must have elapsed from the time of any antibody therapy that could affect an
             anti cancer immune response, including anti-cytotoxic T-lymphocyte antigen 4 (CTLA4)
             antibody therapy, toat the time the patient receives the preparative regimen to allow
             antibody levels to decline.

        Note: Patients who have previously received ipilimumab and have documented gastrointestinal
        (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

        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 left ventricular ejection fraction (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