Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)

Inclusion Criteria

-INCLUSION CRITERIA:

1. Measurable metastatic melanoma with at least one lesion that is resectable for TIL
generation. The lesion must be of at least 1cm in diameter that can be surgically
removed with minimal morbidity (defined as any operation for which expected
hospitalization less than or equal to 7 days).

2. Patients with 3 or less brain metastases are eligible. Note: If lesions are
symptomatic or greater than or equal to 1 cm each, these lesions must have been
treated and stable for 3 months for the patient to be eligible.

3. Greater than or equal to 18 years of age.

4. Willing to practice birth control during treatment and for four months after
receiving all protocol related therapy.

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 ECOG 0 or 1.

9. Hematology:

- Absolute neutrophil count greater than 1000/mm(3)

- Hemoglobin greater than 8.0 g/dl

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

10. 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, or hepatitis C antibody or antigen.

11. Chemistry:

- Serum ALT/AST less than three times the upper limit of normal.

- Calculated creatinine clearance (eGFR) > 50 ml/min.

- 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
of randomization, and patients toxicities must have recovered to a grade 1 or less
(except for alopecia or vitiligo). Patients must have stable or progressing disease
after prior treatment.

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
inclusion criteria.

13. Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow
antibody levels to decline.

14. Patients who have previously received any anti-CTLA4 antibody and have documented GI
toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Prior cell transfer therapy which included a non-myeloablative or myeloablative
chemotherapy regimen.

2. Women of child-bearing potential who are pregnant or breastfeeding because 10 of the
potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

3. Systemic steroid therapy requirement.

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 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 LVEF less than or equal to 45%.

10. In patients > 60 years old, documented LVEF of less than or equal to 45%.

11. Documented FEV1 less than or equal to 60% predicted tested in patients with:

- A prolonged history of cigarette smoking

- Symptoms of respiratory dysfunction

12. Prior radiation therapy that, in the judgment of the radiation oncologist, precludes
the administration of total body irradiation.