Vaccination of Stage IV Cutaneous Melanoma Patients With Mature, Autologous Monocyte-Derived Dendritic Cells Transfected With RNAs Encoding for Mage-3, MelanA, and Survivin Antigens
Collecte de données
Mélanome cutané malin+9
+ Mélanome
+ Néoplasmes germinaux et embryonnaires
Étude thérapeutique
Résumé
Date de début de l'étude : 1 juillet 2003
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: Primary * Determine the safety and tolerability of vaccination with autologous monocyte-derived dendritic cells (DC) transfected with RNAs encoding Melan-A, MAGE-3, and survivin antigens in patients with stage IV cutaneous melanoma. * Determine whether tumor antigen-specific T-cell responses are induced in patients treated with this vaccine. * Determine whether simultaneous loading of DC with keyhole limpet hemocyanin (KLH) significantly enhances induction of the Melan-A, MAGE-3, and survivin antigens in these patients. Secondary * Determine clinical antitumor activity (e.g., objective tumor response, time to tumor progression, progression-free interval, and overall survival) in patients treated with this vaccine. OUTLINE: This is an open-label, nonrandomized study. * Phase I: Beginning 9-11 days before vaccination, patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are processed for the generation of dendritic cells (DC) to be used for vaccinations. PBMCs are transfected with RNAs encoding for Melan-A, MAGE-3, and survivin antigens. DC are pulsed with keyhole limpet hemocyanin (KLH) for some patients. Patients receive antigen-pulsed (with or without KLH) DC vaccination subcutaneously (SC) on days 1, 15, 43, and 71 in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may proceed to the phase II portion of the study. * Phase II: Patients undergo leukapheresis as in phase I on days 102, 354, and 690. Patients receive up to 6 additional booster vaccinations SC as in phase I on days 127, 185, 269, 356, 521, and 692. Patients are followed for 10 years. PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.
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.82 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.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 18 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: * Histologically confirmed cutaneous\* melanoma * Stage IV * Incurable by surgical resection * Progressive disease after at least 1 standard chemotherapy or chemoimmunotherapy regimen (e.g., dacarbazine or cisplatin monotherapy) * Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or noninvasive radiological procedures * No active CNS metastases by CT scan or MRI * Previously treated (e.g., excision of a single metastasis) CNS metastases are allowed provided there are no signs of active CNS metastases NOTE: \*Metastatic melanoma with unidentified primary tumor allowed provided an ocular melanoma can be definitely excluded and origin from the skin is likely PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * At least 4 months Hematopoietic * WBC greater than 2,500/mm\^3 * Neutrophil count greater than 1,000/mm\^3 * Lymphocyte count greater than 700/mm\^3 * Platelet count greater than 75,000/mm\^3 * Hemoglobin greater than 9 g/dL * No bleeding disorder Hepatic * Bilirubin less than 2.0 mg/dL * No evidence of hepatitis B or C infection Renal * Creatinine less than 2.5 mg/dL Cardiovascular * No clinically significant heart disease Pulmonary * No respiratory disease Immunologic * HIV-1 and HIV-2 negative * HTLV-1 negative * No active systemic infection * No immunodeficiency disease * No active autoimmune disease (e.g., lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, or inflammatory bowel disease) * Vitiligo allowed Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 4 weeks after study participation * Stable medical condition * No other major serious illness * No contraindication to leukapheresis * No organic brain syndrome or significant psychiatric abnormality that would preclude study participation or follow-up * No other active malignant neoplasm PRIOR CONCURRENT THERAPY: Biologic therapy * More than 4 weeks since prior immunotherapy * No other concurrent immunotherapy during and for 2 weeks after study participation Chemotherapy * More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas \[e.g., fotemustine\]) * No concurrent chemotherapy during and for 2 weeks after study participation Endocrine therapy * No concurrent corticosteroids during and for 2 weeks after study participation Radiotherapy * More than 2 weeks since prior radiotherapy * No prior radiotherapy to the spleen * Concurrent palliative radiotherapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed Surgery * Recovered from prior surgery * No prior splenectomy * No prior organ allografts * Concurrent surgical therapy to selected metastases (e.g., due to pain or local complications such as compression) is allowed * Selected accessible metastases may be removed for tumor infiltrating lymphocyte assay or other immunomonitoring investigations (e.g., expression of tumor antigens and HLA molecules) Other * No other concurrent investigational drug or paramedical substance during and for 2 weeks after study participation * No concurrent participation in another clinical trial * Concurrent palliative medication allowed (e.g., acetaminophen, indomethacin, or opiates)
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 1 site