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: Phase II trial to study the effectiveness of combining cyclophosphamide with fludarabine as lymphocyte-depleting (decreasing white blood cells) therapy followed by high-dose interleukin-2 in treating patients who have metastatic melanoma.

Condition	Treatment or Intervention	Phase
Recurrent Melanoma Stage IV Melanoma	Drug: cyclophosphamide  Drug: fludarabine  Drug: interleukin-2  Drug: sargramostim  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: interleukin therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed melanoma
• Metastatic disease
• Measurable disease
• No history of brain metastases

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• 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

Hepatic

• AST ≤ 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

Renal

• 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

• FEV_1 ≥ 2.0 liters OR at least 75% of predicted for height and age
• DLCO ≥ 60%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• 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)

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 4 weeks since prior immunotherapy and recovered
• No prior interleukin-2
• No other concurrent anticancer biologic agents

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No concurrent chemotherapy

Endocrine therapy

• At least 4 weeks since prior steroid therapy
• No concurrent corticosteroids

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior surgery and recovered

Other

• No concurrent immunosuppressive therapy

New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting

Study chairs or principal investigators

Marc Stuart Ernstoff, MD,  Study Chair,  Norris Cotton Cancer Center   

Study ID Numbers:  CDR0000370788; DMS-0320; DMS-16531; NCT00085423
Record last reviewed:  May 2004
Last Updated:  December 6, 2004
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085423
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08