Treatment Of Patients With Metastatic Melanoma Using Nonmyeloablative But Lymphocyte Depleting Regimen Followed By The Administration Of In Vitro Sensitized Lymphocytes Reactive With ESO-1 Antigen
Data Collection
Melanoma+9
+ Neoplasms
+ Neoplasms by Histologic Type
Treatment Study
Summary
Study start date: January 1, 2004
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the clinical tumor regression in patients with metastatic melanoma treated with a lymphocyte-depleting nonmyeloablative preparative chemotherapy regimen followed by autologous lymphocyte infusion, ESO-1 peptide vaccination comprising ESO-1:157-165 (165V) and Montanide ISA-51, and interleukin-2. Secondary * Determine the survival of the infused lymphocytes in patients treated with this regimen. * Determine the long-term immune status of patients treated with this regimen. OUTLINE: Patients are stratified according to type of lymphocyte infusion (ESO-1-reactive tumor-infiltrating lymphocytes \[TIL\] vs ESO-1 reactive peripheral blood lymphocytes \[PBL\]). * Autologous lymphocyte collection and expansion: Autologous PBL or TIL are collected from patients during leukapheresis or biopsy. The cells are sensitized in vitro with ESO-1:157-165 (165V) melanoma antigen and expanded. * Lymphocyte-depleting nonmyeloablative preparative chemotherapy: Patients receive lymphocyte-depleting nonmyeloablative preparative chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 15-30 minutes on days -5 to -1. * Autologous lymphocyte infusion: Autologous PBL or TIL are reinfused on day 0\*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. * ESO-1 peptide vaccination: Patients receive ESO-1 peptide vaccination comprising ESO-1:157-165 (165V) peptide emulsified in Montanide ISA-51 SC on days 0\*-4, 11, 18, and 25. * Interleukin therapy: Patients receive interleukin-2 IV over 15 minutes 3 times daily on days 0\*-4. NOTE: \*Day 0 is 1-4 days after the last dose of fludarabine. Patients achieving stable disease or partial response may receive up to 1 retreatment course. Patients with progressive disease after infusion of PBL may receive retreatment with TIL, if available. Patients are followed at 4-5 weeks, every 3-4 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 24-74 patients (12-37 per stratum) will be accrued for this study within 2-3 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 16 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Diagnosis of metastatic melanoma that is refractory to standard therapy (including high-dose interleukin-2) * Measurable disease * HLA-A\*0201 positive * Epstein-Barr virus positive * ESO-1-expressing disease by reverse transcription polymerase chain reaction amplified tissue OR presence of ESO-1 serum antibody PATIENT CHARACTERISTICS: Age * 16 and over Performance status * ECOG 0-1 Life expectancy * More than 3 months Hematopoietic * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL Hepatic * Hepatitis B surface antigen negative * Hepatitis C antibody negative * AST and ALT \< 3 times upper limit of normal * Bilirubin ≤ 2.0 mg/dL (\< 3.0 mg/dL for patients with Gilbert's syndrome) * No coagulation disorders Renal * Creatinine ≤ 2.0 mg/dL Cardiovascular * No prior myocardial infarction * No major cardiovascular illness by stress thallium or comparable test * No cardiac arrhythmias * LVEF ≥ 45% * Normal cardiac stress test required for the following conditions: * Prior EKG abnormalities * Symptoms of cardiac ischemia * Arrhythmias * Age 50 and over Pulmonary * FEV\_1 \> 60% of predicted (for patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction) * No obstructive or restrictive pulmonary disease * No other major respiratory illness Immunologic * HIV negative * No active systemic infection * No opportunistic infection * No major immune system illness * No form of primary or secondary immunodeficiency * No known hypersensitivity to study agents Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 4 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * Prior ESO-1-based vaccination allowed Chemotherapy * At least 6 weeks since prior nitrosoureas and recovered Endocrine therapy * No concurrent systemic steroid therapy Radiotherapy * Recovered from prior radiotherapy Surgery * Not specified Other * At least 4 weeks since prior systemic therapy
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, United StatesOpen Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support in Google MapsNCI - Center for Cancer Research
Bethesda, United States