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

Phase 2CompletedNCT00062036

National Institutes of Health Clinical Center (CC)33 enrolled

Overview

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).

OBJECTIVES: Primary * Determine the survival of patients with metastatic melanoma administered interleukin-2 gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine. * Compare survival results with prior Surgery Branch studies using adoptive cell therapy without the interleukin-2 retroviral vector (SBIL-2) gene. Secondary * Determine clinical tumor regression in patients administered interleukin-2 gene-modified TIL after cyclophosphamide and fludarabine followed by interleukin-2. * Determine the toxicity profile of this regimen in these patients. OUTLINE: * Phase I (closed to accrual as of 3/29/06): * Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over a period of approximately 4 weeks. * Nonmyeloablative preparative regimen (chemotherapy): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1. * Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30 minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, , until blood counts recover. * Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on disease status after each regimen. Patients with dose-limiting toxicity do not receive further treatment. * No response: Patients with stable disease or disease progression after the initial treatment are followed or removed from the study. * Partial response: Patients with a partial or minor response after the initial treatment may receive retreatment, approximately 2-4 weeks later, with chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as above, every 4-6 weeks for up to 2 courses provided at least a partial response is documented after each regimen. * Complete response: Patients with a complete response receive no further treatment. * Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2 gene-transduced TIL. Patients are followed every 3-6 weeks in the absence disease progression. PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes