Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of MART-1 Reactive Peripheral Blood Lymphocytes (PBL) With or Without High Dose Aldesleukin

Inclusion Criteria

-INCLUSION CRITERIA:

1. Measurable metastatic melanoma.

2. Confirmation of diagnosis of metastatic melanoma and positivity for MART confirmed by
the Laboratory of Pathology of the NCI.

3. 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.

4. Patients must be refractory to high dose aldesleukin treatment.

NOTE: This is not required for patients with non-cutaneous melanoma, patients for
whom high dose aldesleukin is medically contraindicated or for patients who are
unwilling to receive high dose aldesleukin.

5. MART-1:27-35 reactive peripheral blood lymphocytes derived from a leukapheresis.

6. HLA-A 0201 positive.

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

8. Both genders must be willing to practice birth control during treatment and for four
months after receiving the preparative regimen.

9. Life expectancy of greater than three months.

10. Willing to sign a durable power of attorney.

11. Able to understand and sign the Informed Consent Document.

12. Clinical performance status of ECOG 0 or 1 for the high-dose aldesleukin cohort or
ECOG 0, 1 or 2 for no aldesleukin cohort.

13. Hematology:

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

- Normal WBC (> 3000/mm(3)).

- Hemoglobin greater than 8.0 g/dl

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

14. 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 or hepatitis C.

15. Chemistry:

- Serum ALT/AST less than less or equal to 3 times the upper limit of normal.

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

- Total bilirubin less than or equal to 2.0 mg/dl, except in patients with
Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.

16. Negative pregnancy test in women of child bearing potential because of the
potentially dangerous effects of the preparative chemotherapy on the fetus.

17. More than four weeks must have elapsed since any prior systemic therapy, including
chemotherapy, immunotherapy, and/or other targeted therapies, 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 within the past 3 weeks, as long as patients
meet eligibility criteria

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

19. Patients who have previously received anti-CTLA4 antibody and experienced treatment
related colitis must have a normal colonoscopy with normal colonic biopsies.

NOTE: this is only required for patients who will receive high dose aldesleukin.

EXCLUSION CRITERIA:

1. 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.

2. Systemic steroid therapy required.

3. 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.

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

5. 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.)

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

7. The following patients will be excluded from the high-dose aldesleukin arm (but may
be eligible for cells alone arm):

1. History of coronary revascularization or ischemic symptoms

2. Any patient known to have an LVEF less than or equal to 45 percent.

3. Documented LVEF of less than or equal to 45 percent 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

4. Documented FEV1 less than or equal to 60 percent predicted tested in patients
with:

- A prolonged history of cigarette smoking (20 pk/yrs of smoking)

- Symptoms of respiratory dysfunction