- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00062036
Cyclophosphamide and Fludarabine Followed By Interleukin-2 Gene-Modified Tumor Infiltrating Lymphocytes in Treating Patients With Metastatic Melanoma
Tumor Infiltrating Lymphocytes (TIL Cells) Transduced With An Interleukin-2 (SBIL-2) Gene Following The Administration Of A Nonmyeloablative But Lymphocyte Depleting Regimen in Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and fludarabine use different ways to stop tumor cells from dividing so they stop growing or die. Inserting the gene for interleukin-2 into a person's tumor infiltrating lymphocytes may make the body build an immune response to kill tumor cells. Combining cyclophosphamide and fludarabine with gene-modified tumor cells may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of gene-modified tumor infiltrating lymphocytes when given together with cyclophosphamide and fludarabine and to see how well they work in patients with metastatic melanoma (phase I is closed to accrual 3/29/06).
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
Primary
- Determine the survival of patients with metastatic melanoma administered interleukin-2 gene-modified tumor infiltrating lymphocytes after cyclophosphamide and fludarabine.
- Compare survival results with prior Surgery Branch studies using adoptive cell therapy without the interleukin-2 retroviral vector (SBIL-2) gene.
Secondary
- Determine clinical tumor regression in patients administered interleukin-2 gene-modified TIL after cyclophosphamide and fludarabine followed by interleukin-2.
- Determine the toxicity profile of this regimen in these patients.
OUTLINE:
Phase I (closed to accrual as of 3/29/06):
- Harvest: TIL are harvested, transduced with IL-2 gene, and expanded in vitro over a period of approximately 4 weeks.
- Nonmyeloablative preparative regimen (chemotherapy): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Lymphocyte administration: Patients receive IL-2 gene-transduced TIL IV over 20-30 minutes on day 0. They also receive high-dose IL-2 IV over 15 minutes every 8 hours on days 0 -5 (maximum 15 doses). Beginning 1-2 days after lymphocyte administration, patients receive filgrastim (G-CSF) subcutaneously (SC) daily, , until blood counts recover.
Retreatment: Patients are re-evaluated every 4-6 weeks. Retreatment depends on disease status after each regimen. Patients with dose-limiting toxicity do not receive further treatment.
- No response: Patients with stable disease or disease progression after the initial treatment are followed or removed from the study.
- Partial response: Patients with a partial or minor response after the initial treatment may receive retreatment, approximately 2-4 weeks later, with chemotherapy, IL-2 gene-transduced TIL, immunization, and high-dose IL-2 as above, every 4-6 weeks for up to 2 courses provided at least a partial response is documented after each regimen.
- Complete response: Patients with a complete response receive no further treatment.
- Phase II: Patients receive treatment and retreatment as in phase I with the MTD of IL-2 gene-transduced TIL.
Patients are followed every 3-6 weeks in the absence disease progression.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Maryland
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Bethesda, Maryland, Estados Unidos, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
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Bethesda, Maryland, Estados Unidos, 20892
- NCI - Center for Cancer Research
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
DISEASE CHARACTERISTICS:
Diagnosis of melanoma
- Metastatic disease
- Refractory to standard therapy including high-dose interleukin-2 (IL-2) therapy
- Evaluable disease
- Patients may enroll at the cell infusion stage provided they have tumor available for biopsy OR expandable SBIL-2-transduced tumor infiltrating lymphocytes available
- Progressive disease during prior immunization to melanoma antigens or cellular therapy, with or without myeloablation, allowed
- Symptomatic CNS lesions allowed provided immediate active treatment for symptomatic lesions has been completed
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count greater than 1,000/mm^3
- WBC greater than 3,000/mm^3
- Lymphocyte count greater than 500/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin greater than 8.0 g/dL
- No coagulation disorder
Hepatic
- Bilirubin no greater than 2.0 mg/dL (less than 3.0 mg/dL in patients with Gilbert's syndrome)
- AST/ALT less than 3 times upper limit of normal
- Hepatitis B surface antigen negative
- Hepatitis C virus negative
Renal
- Creatinine no greater than 1.6 mg/dL
Cardiovascular
- No myocardial infarction
- No cardiac arrhythmias
- No abnormal stress thallium or comparable test
LVEF > 45% and normal stress cardiac test in patients with the following criteria:
- 50 years old or greater
- History of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias
- No major cardiovascular illness
Pulmonary
- No obstructive or restrictive pulmonary disease
- No major respiratory illness
- FEV_1 > 60% predicted in patients with prolonged history of cigarette smoking or symptoms of respiratory dysfunction
Immunologic
- HIV negative
- No prior severe immediate hypersensitivity reaction
- No primary or secondary immunodeficiency
- No active systemic infection
- No concurrent opportunistic infection
- No major immune system illness
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 months after study therapy
- Must sign a durable power of attorney
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior anti-cytotoxic T-lymphocyte antibody-4 antibody (CTLA-4) allowed unless post-MDX010 treatment and colonoscopy with colonic biopsies are normal
Chemotherapy
- Recovered from prior chemotherapy
Endocrine therapy
- No concurrent steroids
Radiotherapy
- Recovered from prior radiotherapy
Surgery
- Not specified
Other
- More than 4 weeks since prior systemic therapy
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Enmascaramiento: Ninguno (etiqueta abierta)
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
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Supervivencia
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Medidas de resultado secundarias
Medida de resultado |
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Perfil de toxicidad
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Regresión tumoral clínica
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por tipo histológico
- Neoplasias
- Tumores neuroectodérmicos
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Tumores neuroendocrinos
- Nevos y Melanomas
- Melanoma
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes del sistema nervioso periférico
- Agentes Antivirales
- Agentes Anti-VIH
- Agentes antirretrovirales
- Analgésicos
- Agentes del sistema sensorial
- Analgésicos no narcóticos
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Adyuvantes, Inmunológicos
- Aldesleukin
- Ciclofosfamida
- Fludarabina
- Fosfato de fludarabina
- Interleucina-2
- Adyuvante de Freund
Otros números de identificación del estudio
- 030162
- 03-C-0162
- NCI-5855
- CDR0000304438
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