- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00085423
Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells and may help a person's immune system recover from the side effects of chemotherapy.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with high-dose interleukin-2 works in treating patients with metastatic melanoma.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the objective response rate in lymphodepleted patients with metastatic melanoma treated with cyclophosphamide, fludarabine, and high-dose interleukin-2.
- Determine the feasibility of this regimen in these patients.
Secondary
- Determine the quality and quantity of lymphocyte recovery in these patients during and after treatment with this regimen.
- Determine time to disease progression and survival in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study.
Patients receive lymphodepleting therapy comprising cyclophosphamide IV over 1 hour on days 1 and 2 and fludarabine IV over 30 minutes on days 3-7. Patients then receive high-dose interleukin-2 IV every 8 hours (14 doses) on days 8-12 and 22-26. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 8 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
New Hampshire
-
Lebanon, New Hampshire, Estados Unidos, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Histologically confirmed melanoma
- Metastatic disease
- Measurable disease
- No history of brain metastases
- Over 18
- Karnofsky 60-100%
- Life expectancy At least 12 weeks
- Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3
- Hemoglobin ≥ 8.5 g/dL
- aspartate aminotransferase ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- Bilirubin ≤ 2 times ULN (except for patients with Gilbert's syndrome)
- Hepatitis B and C negative
- Creatinine ≤ 2.0 times ULN
- Creatinine clearance ≥ 50 mL/min
- Cardiovascular
- Ejection fraction ≥ 50%
- No evidence of congestive heart failure
- No symptoms of coronary artery disease
- No serious cardiac arrhythmias
- No myocardial infarction within the past 6 months
- Cardiac stress test negative or of low probability for patients > 40 years of age OR who have had prior myocardial infarction > 6 months ago
- Pulmonary Forced expiratory volume 1 ≥ 2.0 liters OR at least 75% of predicted for height and age
- Diffusing capacity of lung for carbon monoxide ≥ 60%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
Exclusion Criteria:
- No uncontrolled diabetes
- No history of autoimmune disease
- No active infection
- No other concurrent significant illness that would preclude study participation
- No other malignancy within the past 5 years except nonmelanoma skin cancer or non-invasive cancer (e.g., carcinoma in situ of the cervix, superficial bladder cancer without local recurrence, or carcinoma in situ of the breast)
- At least 4 weeks since prior immunotherapy and recovered
- No other concurrent anticancer biologic agents
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
- No concurrent chemotherapy
- At least 4 weeks since prior steroid therapy
- No concurrent corticosteroids
- At least 4 weeks since prior radiotherapy and recovered
- No concurrent radiotherapy
- At least 4 weeks since prior surgery and recovered
- No concurrent immunosuppressive therapy
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: IL-2, CTX, fludarabine, GM-CSF
Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim
|
‡Interleukin-2 (aldesleukin) IV (600,000 U/kg; Chiron, Emeryville, CA): two 5-day courses on days 8 and 22. Interleukin-2 was given over 15 minutes every 8 hours.
Goal is 14 doses/5-day course
Otros nombres:
GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.
Otros nombres:
Cyclophosphamide (60 mg/kg/d; Baxter, Deerfield, IL) intravenously (IV) for 2 days with sodium 2- mercaptoethanesulfonate (Mesna; Sicor, Irvine, CA) at 20% of cyclophosphamide dose IV 15 minutes before and 40% of the cyclophosphamide dose orally at 2 and 6 hours after the initiation of chemotherapy.
Otros nombres:
Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
Periodo de tiempo: Response at 12 weeks
|
Objective response as measured by radiological and physical examination using RECIST criteria.
|
Response at 12 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Number of Participants With Lymphocyte Recovery as Measured by Blood Count
Periodo de tiempo: on days 1-15, weekly for 2 weeks, and then every 2-3 months
|
Lymphocyte recovery to a greater than 1000 cells/mcL was determined by differential peripheral blood cell counts on sequential days as noted in time frame.
|
on days 1-15, weekly for 2 weeks, and then every 2-3 months
|
Time to Progression as Measured by RECIST
Periodo de tiempo: From date of randomization until the first date of documented progression or date of death from any cause, which ever came first, assessed up till 100 months
|
Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.
|
From date of randomization until the first date of documented progression or date of death from any cause, which ever came first, assessed up till 100 months
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Marc S. Ernstoff, MD, Norris Cotton Cancer Center
Publicaciones y enlaces útiles
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 (Estimar)
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
- Aldesleukin
- Ciclofosfamida
- Fludarabina
- Fosfato de fludarabina
- Sargramostim
- Interleucina-2
- Molgramostim
Otros números de identificación del estudio
- CDR0000370788
- P30CA023108 (Subvención/contrato del NIH de EE. UU.)
- DMS-0320 (Otro identificador: Dartmouth-Hitchcock)
- DMS-16531 (Otro identificador: Dartmouth-Hitchcock)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre aldesleukin
-
Onur Boyman, MDTerminadoLupus Eritematoso SistémicoSuiza
-
National Institute of Allergy and Infectious Diseases...TerminadoInfecciones por VIHEstados Unidos
-
National Institute of Allergy and Infectious Diseases...Terminado
-
National Institute of Allergy and Infectious Diseases...Terminado
-
National Institute of Allergy and Infectious Diseases...Terminado
-
National Institute of Allergy and Infectious Diseases...Terminado
-
National Cancer Institute (NCI)TerminadoMelanoma metastásico | Cáncer de células renalesEstados Unidos
-
Chiron CorporationDesconocidoInfecciones por VIHEstados Unidos
-
Chiron CorporationTerminadoInfecciones por VIHEstados Unidos