Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: aldesleukin; sargramostim; cyclophosphamide; fludarabine phosphate
Intervention description: ‡Interleukin-2 (aldesleukin) IV (600,000 U/kg; Chiron, Emeryville, CA): two 5-day courses on days 8 and 22. Interleukin-2 was given over 15 minutes every 8 hours. Goal is 14 doses/5-day course; GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.; Cyclophosphamide (60 mg/kg/d; Baxter, Deerfield, IL) intravenously (IV) for 2 days with sodium 2- mercaptoethanesulfonate (Mesna; Sicor, Irvine, CA) at 20% of cyclophosphamide dose IV 15 minutes before and 40% of the cyclophosphamide dose orally at 2 and 6 hours after the initiation of chemotherapy.; Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Molgramostim; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent melanoma; stage IV melanoma

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.
    

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