Cyclophosphamide and Fludarabine Followed By an Autologous Lymphocyte Infusion and Interleukin-2 in Treating Patients With Refractory or Recurrent Metastatic Melanoma

• Status: Terminated
• Trial end date: 2007-04-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: An infusion of a patient's lymphocytes that have been treated in the laboratory to remove certain immune cells may be an effective treatment for melanoma. Drugs, such as cyclophosphamide and fludarabine, may suppress the immune system so that the patient's immune cells allow the infused lymphocytes to work. Interleukin-2 may help the lymphocytes kill more tumor cells when they are put back in the body. Giving cyclophosphamide and fludarabine followed by an autologous lymphocyte infusion and interleukin-2 may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine followed by an autologous lymphocyte infusion and interleukin-2 works in treating patients with refractory or recurrent melanoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma

• Metastatic disease

• Measurable disease

• HLA-A2 negative disease

• Disease did not respond to OR recurred after completion of prior high-dose interleukin-2 (IL-2)

• Eligible to receive high-dose IL-2

• No tumor reactive cells available for cell transfer therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3

• Platelet count > 100,000/mm^3

• Hemoglobin > 8.0 g/dL

• No coagulation disorders

Hepatic

• ALT and AST < 3 times upper limit of normal

• Bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL if due to Gilbert's syndrome)

• Hepatitis B surface antigen negative

• Hepatitis C antigen negative

Renal

• Creatinine ≤ 2.0 mg/dL

• No renal failure requiring dialysis due to toxic effects of prior IL-2 administration

Cardiovascular

• No myocardial infarction

• No cardiac arrhythmias

• No other major cardiovascular illness as evidenced by a positive stress thallium or comparable test

• Normal cardiac stress test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram) AND LVEF ≥ 45% (for patients ≥ 50 years of age or who have a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmias)

Pulmonary

• No obstructive or restrictive pulmonary disease

• No other major respiratory illness

• FEV_1 ≥ 60% of predicted (for patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction)

Immunologic

• HIV negative

• Epstein-Barr virus positive

• No active systemic infection

• No autoimmune disease (e.g., autoimmune colitis or Crohn's disease)

• No immunodeficiency due to prior chemotherapy or radiotherapy

• Recovered immune competence after prior chemotherapy or radiotherapy as evidenced by normal lymphocyte count and WBC and an absence of opportunistic infection

• No other major immune system disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 4 months after completion of study treatment

• No other toxic effects during prior IL-2 administration that would preclude redosing with IL-2, including the following:

• Mental status changes that would require intubation

• Bowel perforation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• At least 4 weeks since prior systemic therapy

Chemotherapy

• At least 6 weeks since prior nitrosoureas

• At least 4 weeks since prior systemic therapy

Endocrine therapy

• No concurrent systemic steroid therapy

Radiotherapy

• Not specified

Surgery

• Not specified