Treatment of Patients With Metastatic Melanoma by Lymphodepleting Conditioning Followed by Infusion of TCR-Gene Engineered Lymphocytes and Subsequent Fowlpox gp100 Vaccination
Colección de datos
Melanoma+5
+ Neoplasias
+ Neoplasias de Células Germinales y Embrionarias
Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de mayo de 2004
Fecha en la que se inscribió al primer participante.OBJECTIVES: Primary * Determine, preliminarily, any clinical tumor regression in lymphodepleted patients with metastatic melanoma treated with fowlpox gp100 antigen immunization and antitumor antigen T-cell receptor (TCR)-engineered tumor infiltrating lymphocytes or CD8+ autologous peripheral blood lymphocytes followed by interleukin-2. Secondary * Determine the in vivo survival of TCR gene-engineered cells in patients treated with this regimen. OUTLINE: Patients are stratified according to their ability to produce tumor-infiltrating lymphocytes (TIL) (yes vs no). Patients receive lymphodepleting chemotherapy comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1. * Stratum 1 (TIL): Patients receive TIL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0\*. * Stratum 2 (CD8+peripheral blood lymphocytes \[PBL\]): Patients receive CD8+PBL retrovirally transduced with gp100 antigen TCR gene IV over 20-30 minutes on day 0\*. NOTE: \*Day 0 is 1-4 days after the last dose of fludarabine. Patients in both strata also receive fowlpox-gp100 vaccine (before TIL/PBL infusion) IV over 1-2 minutes on days 0 and 28 and high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours on days 0-4 and days 28-32. Patients also receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-8 weeks after the last dose of vaccine and high-dose IL-2, patients with stable or responding disease may receive 1 retreatment course. Responding patients are followed at 1, 3, 6, and 12 months and then annually thereafter. PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 61 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: * Diagnosis of melanoma * Metastatic disease * Measurable disease * Refractory to standard therapy, including high-dose interleukin-2 therapy * HLA-A\*0201 positive * Progressive disease during prior immunization to melanoma antigens OR prior treatment with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) cellular therapy with or without myeloablation allowed provided toxicity resolved to ≤ grade 2 (except vitiligo) AND patient does not require systemic steroids * No brain metastases PATIENT CHARACTERISTICS: Age * 18 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 * Lymphocyte count \> 500/mm\^3 * WBC \> 3,000/mm\^3 * No coagulation disorders Hepatic * AST and ALT \< 3 times upper limit of normal (ULN) * Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL in patients with Gilbert's syndrome) * Hepatitis B surface antigen negative * Hepatitis C antibody negative (unless antigen negative) Renal * Creatinine ≤ 1.6 mg/dL Cardiovascular * LVEF ≥ 45% by cardiac stress test * No LVEF \< 45% in patients ≥ 50 years of age * No myocardial infarction * No cardiac arrhythmias * No symptomatic cardiac ischemia * No prior EKG abnormalities * No other major cardiovascular illness Pulmonary * FEV_1 ≥ 60% of predicted AND no obstructive or restrictive pulmonary disease * No symptoms of respiratory dysfunction * No other major respiratory illness Immunologic * HIV negative * Epstein-Barr virus positive * No active systemic infections (including opportunistic infections) * No form of primary (e.g., autoimmune colitis or Crohn's disease) or secondary immunodeficiency (due to chemotherapy or radiotherapy) * No prior severe immediate hypersensitivity reaction to any of the study agents including eggs * No other major illness of the immune system Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 month after study participation * Willing to complete a durable power of attorney (DPA) PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * More than 6 weeks since prior MDX-010 Chemotherapy * Not specified Endocrine therapy * See Disease Characteristics * No concurrent systemic steroid therapy Radiotherapy * Not specified Surgery * Not specified Other * More than 4 weeks since other prior systemic therapy and recovered
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 2 ubicaciones
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, United StatesVer ubicaciónNCI - Surgery Branch
Bethesda, United States