Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma

• Status: Completed
• Trial end date: 2008-09-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase I is closed to accrual 3/29/06).

• Phase: Phase 1/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; Freund's Adjuvant; Interleukin-2

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of melanoma

• Metastatic disease

• Refractory to standard therapy including high-dose interleukin-2 (IL-2) therapy

• Evaluable disease

• Patients may enroll at the cell infusion stage provided they have tumor available for biopsy OR expandable SBIL-2-transduced tumor infiltrating lymphocytes available

• Progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed

• Symptomatic CNS lesions allowed provided immediate active treatment for symptomatic lesions has been completed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3

• WBC greater than 3,000/mm^3

• Lymphocyte count greater than 500/mm^3

• Platelet count greater than 100,000/mm^3

• Hemoglobin greater than 8.0 g/dL

• No coagulation disorder

Hepatic

• Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome)

• AST/ALT less than 3 times upper limit of normal

• Hepatitis B surface antigen negative

• Hepatitis C virus negative

Renal

• Creatinine no greater than 1.6 mg/dL

Cardiovascular

• No myocardial infarction

• No cardiac arrhythmias

• No abnormal stress thallium or comparable test

• LVEF > 45% and normal stress cardiac test in patients with the following criteria:

• 50 years old or greater

• History of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias

• No major cardiovascular illness

Pulmonary

• No obstructive or restrictive pulmonary disease

• No major respiratory illness

• FEV_1 > 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction

Immunologic

• HIV negative

• No prior severe immediate hypersensitivity reaction

• No primary or secondary immunodeficiency

• No active systemic infection

• No concurrent opportunistic infection

• No major immune system illness

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 4 months after study therapy

• Must sign a durable power of attorney

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• No prior anti-cytotoxic T-lymphocyte antibody-4 antibody (CTLA-4) allowed unless post-MDX010 treatment and colonoscopy with colonic biopsies are normal

Chemotherapy

• Recovered from prior chemotherapy

Endocrine therapy

• No concurrent steroids

Radiotherapy

• Recovered from prior radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior systemic therapy