Combination Chemotherapy With or Without Bortezomib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
A Parallel Randomised Phase II Trial of CHOP Chemotherapy With or Without Bortezomib in Relapsed Mantle Cell Lymphoma
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bortezomib may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without bortezomib in treating mantle cell lymphoma.
PURPOSE: This randomized phase II trial is studying combination chemotherapy and bortezomib to see how well they work compared with combination chemotherapy alone in treating patients with relapsed or refractory mantle cell lymphoma. Combination chemotherapy alone (Arm I) has been discontinued April 2012 on recommendation of the DMC.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
OBJECTIVES:
Primary
- To evaluate the rates of overall response (complete response [CR], CR unconfirmed [CRu], and partial response).
Secondary
- To evaluate the rates of CR and CRu.
- To determine the median time to progression.
- To determine the median overall survival.
- To evaluate the toxicity and tolerability.
- To compare the responses to these treatment regimens with those from first line therapy.
- To compare the quality of life.
OUTLINE: This is a randomized, open-label, parallel group, multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I (CHOP): Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Arm I has been discontinued April 2012 on recommendation of the DMC.
- Arm II (CHOP with bortezomib): Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5.
In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment.
After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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England
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Basingstoke, England, Reino Unido, RG24 9NA
- Basingstoke and North Hampshire NHS Foundation Trust
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Birmingham, England, Reino Unido, B9 5SS
- Birmingham Heartlands Hospital
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Birmingham, England, Reino Unido, B75 7RR
- Good Hope Hospital
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Blackpool, England, Reino Unido, FY3 8NR
- Blackpool Victoria Hospital
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Cambridge, England, Reino Unido, CB2 2QQ
- Addenbrooke's Hospital
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Dartford, England, Reino Unido, DA2 8DA
- Darent Valley Hospital
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Harrogate, England, Reino Unido, HG2 7SX
- Harrogate District Hospital
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Leeds, England, Reino Unido, LS1 3EX
- Leeds General Infirmary
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Liverpool, England, Reino Unido, L7 8XP
- Royal Liverpool University Hospital
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London, England, Reino Unido, SE1 9RT
- Guy's Hospital
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Maidstone, England, Reino Unido, ME16 9QQ
- Mid Kent Oncology Centre at Maidstone Hospital
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Newcastle-Upon-Tyne, England, Reino Unido, NE1 4LP
- Royal Victoria Infirmary
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Norfolk, England, Reino Unido, NR31 6LA
- James Paget Hospital
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Norwich, England, Reino Unido, NR4 7UY
- Norfolk and Norwich University Hospital
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Plymouth, England, Reino Unido, PL6 8DH
- Derriford Hospital
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Prescot Merseyside, England, Reino Unido, L35 5DR
- Whiston Hospital
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Southampton, England, Reino Unido, SO16 6YD
- Southampton General Hospital
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Sunderland, England, Reino Unido, SR4 7TP
- Sunderland Royal Hospital
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Taunton, England, Reino Unido, TA1 5DA
- Musgrove Park Hospital
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Torquay, England, Reino Unido, TQ2 7AA
- Torbay Hospital
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Truro, Cornwall, England, Reino Unido, TR1 3LJ
- Royal Cornwall Hospital
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Scotland
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Aberdeen, Scotland, Reino Unido, AB25 2ZN
- Aberdeen Royal Infirmary
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Inverness, Scotland, Reino Unido, 1V2 3UJ
- Raigmore Hospital
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Wales
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Bangor, Wales, Reino Unido, LL57 2PW
- Ysbyty Gwynedd
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Llanelli, Wales, Reino Unido, SA14 8QF
- Prince Philip Hospital
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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 mantle cell lymphoma (MCL)
- Expression of cyclin D1 or evidence of t(11;14) translocation by cytogenetics, FISH, or polymerase chain reaction
- Refractory to or relapsed or progressed after first line antineoplastic therapy
- Measurable disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2
- ANC ≥ 1,000/mm³ (not related to lymphoma)
- Platelet count ≥ 30,000/mm³
- AST and ALT ≤ 3 times upper limit of normal (ULN)
- Total bilirubin ≤ 2 times ULN
- Creatinine clearance ≥ 20 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- Known serological positivity for HBV, HCV, or HIV
- History of allergic reaction attributable to compounds containing boron or mannitol
- Diagnosed or treated for a malignancy other than MCL within the past 5 years except for completely resected basal cell or squamous cell carcinoma of the skin or any in situ malignancy
- Active systemic infection requiring treatment
- Serious medical or psychiatric illness that would preclude study participation
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- Toxic effects of prior therapy or surgery must be resolved to ≤ grade 2
- Prior splenectomy or localized radiotherapy allowed
Any prior chemotherapy regimen allowed
- Chemotherapy may have been given in combination with rituximab
- Concurrent enrollment in a nontreatment study allowed, provided it does not interfere with participation in this study
Exclusion criteria:
- Prior bortezomib
- Antineoplastic therapy within the past 3 weeks
- Nitrosoureas within the past 6 weeks
- Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody within the past 4 weeks
- Radiotherapy within the past 3 weeks
- Major surgery within the past 2 weeks
- Concurrent investigational agents
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: Bortezomib plus CHOP
Patients receive bortezomib IV over 3-5 seconds on days 1 and 8; doxorubicin hydrochloride IV, cyclophosphamide IV, and vincristine IV on day 1; and oral prednisolone on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires at baseline, prior to each treatment course, and then at 30 days after completion of treatment. After completion of study treatment, patients are followed at 30 days and then every 12 weeks thereafter. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Disease progression
Periodo de tiempo: 30 days and every 12 weeks
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The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
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30 days and every 12 weeks
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Unacceptable toxicity or tolerability as assessed by NCI CTCAE v3.0
Periodo de tiempo: continual after first drug dose
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The follow-up visits will be at 30 days after last dose of study drug and after that every 12 weeks until: Progressive disease, initiation of further anti-neoplastic therapy, patient decision to withdraw from the study, patient death.
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continual after first drug dose
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Simon Rule, MD, Derriford Hospital
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
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Linfoma No Hodgkin
- Linfoma
- Linfoma De Células Del Manto
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Moduladores de tubulina
- Agentes antimitóticos
- Moduladores de mitosis
- Glucocorticoides
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Agentes antineoplásicos, fitogénicos
- Inhibidores de la topoisomerasa II
- Inhibidores de la topoisomerasa
- Antibióticos, Antineoplásicos
- Prednisolona
- Ciclofosfamida
- Bortezomib
- Doxorrubicina
- Doxorrubicina liposomal
- Vincristina
Otros números de identificación del estudio
- CDR0000559820
- NCRN-Ply-26s
- EU-20747
- ISRCTN200600609024
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