Conditions: Melanoma (Skin)
Keywords: recurrent melanoma stage IV melanoma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 20
Healthy volunteers: no

Brief 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.

Detailed description:
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.

Arms:
arm 1: Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim

Interventions: intervention 1: aldesleukin intervention 2: sargramostim intervention 3: cyclophosphamide intervention 4: fludarabine phosphate
Intervention descriptions: intervention 1: ‡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 intervention 2: GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days. intervention 3: 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. intervention 4: Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3

Protocol document: