Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with high-dose interleukin-2 works in treating patients with metastatic melanoma.

OBJECTIVES:

Primary

* Determine the objective response rate in lymphodepleted patients with metastatic melanoma treated with cyclophosphamide, fludarabine, and high-dose interleukin-2.
* Determine the feasibility of this regimen in these patients.

Secondary

* Determine the quality and quantity of lymphocyte recovery in these patients during and after treatment with this regimen.
* Determine time to disease progression and survival in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive lymphodepleting therapy comprising cyclophosphamide IV over 1 hour on days 1 and 2 and fludarabine IV over 30 minutes on days 3-7. Patients then receive high-dose interleukin-2 IV every 8 hours (14 doses) on days 8-12 and 22-26. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 8 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed melanoma
* Metastatic disease
* Measurable disease
* No history of brain metastases
* Over 18
* Karnofsky 60-100%
* Life expectancy At least 12 weeks
* Hematopoietic
* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 75,000/mm\^3
* Hemoglobin ≥ 8.5 g/dL
* aspartate aminotransferase ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
* Bilirubin ≤ 2 times ULN (except for patients with Gilbert's syndrome)
* Hepatitis B and C negative
* Creatinine ≤ 2.0 times ULN
* Creatinine clearance ≥ 50 mL/min
* Cardiovascular
* Ejection fraction ≥ 50%
* No evidence of congestive heart failure
* No symptoms of coronary artery disease
* No serious cardiac arrhythmias
* No myocardial infarction within the past 6 months
* Cardiac stress test negative or of low probability for patients \> 40 years of age OR who have had prior myocardial infarction \> 6 months ago
* Pulmonary Forced expiratory volume 1 ≥ 2.0 liters OR at least 75% of predicted for height and age
* Diffusing capacity of lung for carbon monoxide ≥ 60%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative

Exclusion Criteria:

* No uncontrolled diabetes
* No history of autoimmune disease
* No active infection
* No other concurrent significant illness that would preclude study participation
* No other malignancy within the past 5 years except nonmelanoma skin cancer or non-invasive cancer (e.g., carcinoma in situ of the cervix, superficial bladder cancer without local recurrence, or carcinoma in situ of the breast)
* At least 4 weeks since prior immunotherapy and recovered
* No other concurrent anticancer biologic agents
* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
* No concurrent chemotherapy
* At least 4 weeks since prior steroid therapy
* No concurrent corticosteroids
* At least 4 weeks since prior radiotherapy and recovered
* No concurrent radiotherapy
* At least 4 weeks since prior surgery and recovered
* No concurrent immunosuppressive therapy