Phase II Study of Short-Term Cultured Anti-Tumor Autologous Lymphocytes After Lymphocyte-Depleting Chemotherapy in Metastatic Melanoma

-INCLUSION CRITERIA:

1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation.
2. Patients with one to three brain metastases are eligible (lesions greater than or equal to 1 cm each, or symptomatic lesions must have been treated and stable for 3 months).
3. Greater than or equal to 18 years of age .
4. Willing to practice birth control during treatment and for four months after receiving the preparative regimen.
5. Life expectancy of greater than three months.
6. Willing to sign a durable power of attorney.
7. Able to understand and sign the Informed Consent Document.
8. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
9. Hematology:

   * Absolute neutrophil count greater than 1000/mm\^3 without support of filgrastim.
   * Normal white blood cell (WBC) (greater than 3000/ mm\^3).
   * Hemoglobin greater than 8.0 g/dl.
   * Platelet count greater than 100,000/ mm\^3.
10. 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 or hepatitis C.
11. Chemistry: . Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal. Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
12. 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). Patients may have undergone minor surgical procedures with 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 2.1.1.
13. Six weeks must have elapsed since prior MDX-010 (Ipilimumab) therapy to allow antibody levels to decline.
14. Patients who have previously received any anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody and experienced treatment related colitis must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Prior cell transfer therapy that included non-myeloablative or ablative chemotherapy (for cohorts 4 and 5).
2. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
3. Systemic steroid therapy required.
4. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and Acquired Immune Deficiency Syndrome (AIDS)).
6. 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.)
7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
8. History of coronary revascularization or ischemic symptoms.
9. Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
10. Documented LVEF of less than or equal to 45% tested 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.
11. Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:

    * A prolonged history of cigarette smoking
    * Symptoms of respiratory dysfunction