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
Colección de datos
Melanoma cutáneo maligno+6
+ Melanoma
+ Neoplasias
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de julio de 2003
Fecha en la que se inscribió al primer participante.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.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 82 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.A partir de 18 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
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 Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.Objetivos del Estudio
Objetivos Primarios
Objetivos Secundarios
Centros del Estudio
Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.Este estudio tiene una ubicación
Dermatologische Klinik mit Poliklinik - Universitaetsklinikum Erlangen
Erlangen, GermanyVer ubicación