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
Collecte de données
Mélanome+9
+ Néoplasmes germinaux et embryonnaires
+ Néoplasmes par type histologique
Étude thérapeutique
Résumé
Date de début de l'étude : 1 janvier 2004
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 16 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Objectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 2 sites
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, United StatesOuvrir Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support dans Google MapsNCI - Center for Cancer Research
Bethesda, United States