Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma
A Phase II Trial With VELCADE® (PS-341), Cytoxan (Cyclophosphamide), Dexamethasone and Thalomid® (VEL-CTD) in Previously Untreated Multiple Myeloma Patients
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bortezomib together with cyclophosphamide, dexamethasone, and thalidomide works in treating patients with newly diagnosed, previously untreated multiple myeloma.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
OBJECTIVES:
Primary
- Determine the response rate in patients with newly diagnosed, previously untreated multiple myeloma treated with bortezomib, cyclophosphamide, dexamethasone, and thalidomide.
Secondary
- Determine the safety and tolerability of this regimen in these patients.
OUTLINE: This is an open-label, multicenter study.
Patients receive bortezomib IV on days 1, 4, 8, and 11; cyclophosphamide IV on days 1 and 8 of courses 1-3; oral thalidomide once daily on days 1-21 beginning in course 4; and dexamethasone IV or orally once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Berkeley, California, Estados Unidos, 94704
- Alta Bates Summit Comprehensive Cancer Center
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Los Angeles, California, Estados Unidos, 90048
- Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
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Palm Springs, California, Estados Unidos, 92262
- Desert Regional Medical Center Comprehensive Cancer Center
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Sacramento, California, Estados Unidos, 95816
- Sutter Cancer Center
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Florida
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Boca Raton, Florida, Estados Unidos, 33486
- Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
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New York
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New York, New York, Estados Unidos, 10011
- St. Vincent's Comprehensive Cancer Center - Manhattan
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Oregon
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Portland, Oregon, Estados Unidos, 97239
- Oregon Health and Science University Cancer Institute
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Texas
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Austin, Texas, Estados Unidos, 78759
- Lone Star Oncology - Austin
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Washington
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Seattle, Washington, Estados Unidos, 98109-1023
- Seattle Cancer Care Alliance
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Seattle, Washington, Estados Unidos, 98109-1024
- Fred Hutchinson Cancer Research Center
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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 multiple myeloma meeting 1 of the following criteria:
Monoclonal immunoglobulin spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL) and kappa or lambda light chain excretion > 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:
- Bone marrow plasmacytosis (10-30% plasma cells)
- Lytic bone lesions
Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:
- Lytic bone lesions
- IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
Bone marrow plasmacytosis (> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:
- Monoclonal immunoglobulin of lesser magnitude present
- Lytic bone lesions
- IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
- FreeLite testing abnormal and kappa:lambda light chain ratio abnormal
Symptomatic disease requiring treatment
- Documented related organ or tissue involvement, if present
Measurable disease, defined as 1 of the following:
- Monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/day
- Abnormal FreeLite testing (for nonsecretors)
Patients with nonsecretory disease must meet either of the following criteria for measurability:
- Has measurable protein by FreeLite testing
- Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow
- Newly diagnosed, previously untreated disease
- No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
- No plasma cell leukemia
PATIENT CHARACTERISTICS:
- Karnofsky performance status 50-100%
Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ if bone marrow is extensively infiltrated)
- Extensive infiltration is defined as > 50% myeloma cells or plasma cells
- Hemoglobin ≥ 8.5 g/dL
- Absolute neutrophil count ≥ 1,500/mm³
- AST and ALT ≤ 2 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN (unless clearly related to the disease)
- Creatinine clearance ≥ 20 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use 2 methods of effective contraception ≥ 4 weeks prior to beginning treatment, during, and for ≥ 4 weeks after completion of study treatment
- No impaired kidney function requiring dialysis
- No uncontrolled infection
- No HIV positivity
- No known active hepatitis B or C
No cardiovascular disease including, but not limited to, any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class II-IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Clinically significant pericardial disease
- Acute ischemic or active conduction system abnormalities by EKG
- No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide
- No second malignancy requiring concurrent treatment
- No other serious medical or psychiatric illness that would preclude study compliance
- No peripheral neuropathy ≥ grade 1
PRIOR CONCURRENT THERAPY:
No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma
- Drugs given to prevent onset of myeloma allowed
- Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed
- Prior local radiotherapy with or without a brief exposure to steroids allowed
More than 4 weeks since prior and no concurrent radiotherapy
- Spot radiotherapy to ≤ 3 vertebrae allowed
- No concurrent steroids at > 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)
- No other concurrent chemotherapy or investigational agents
- Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment
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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Tasa de respuesta
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Medidas de resultado secundarias
Medida de resultado |
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Seguridad y tolerabilidad
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: William I. Bensinger, MD, Fred Hutchinson Cancer Center
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
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
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Enfermedades hematológicas
- Trastornos hemorrágicos
- Trastornos hemostáticos
- Paraproteinemias
- Trastornos de proteínas en sangre
- Mieloma múltiple
- Neoplasias De Células Plasmáticas
- Plasmacitoma
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Autonómicos
- Agentes del sistema nervioso periférico
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Antieméticos
- Agentes Gastrointestinales
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Agentes antibacterianos
- Agentes leprostáticos
- Dexametasona
- Ciclofosfamida
- Talidomida
- Bortezomib
Otros números de identificación del estudio
- CDR0000536219
- FHCRC-2123.00
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