cyclophosphamide, fludarabine, and high-dose interleukin-2 in treating patients with metastatic melanoma

Conditions: Melanoma (Skin)

Summary: 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

Keywords: recurrent melanoma stage iv melanoma