Assessment of Efficacy and Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab Chemoimmunotherapy in Young Patients With Chronic Lymphocytic Leukemia. (CLL0911)
12 de octubre de 2020 actualizado por: Gruppo Italiano Malattie EMatologiche dell'Adulto
Phase 2 Multicenter, Study to Assess the Efficacy and the Safety of Front-line Fludarabine, Cyclophoshamide and Ofatumumab (FCO2) Chemoimmunotherapy in Young (≤65 Yrs) Patients With Chronic Lymphocytic Leukemia (CLL).
Assessment of safety and efficacy of with fludarabine and cyclophosphamide (FC) combined with ofatumumab (FCO2) in previously untreated "young" patients with Chronic Lymphocytic Leukemia (CLL).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
Given that:
- rituximab, fludarabine and cyclophosphamide (FCR) front-line treatment was associated with a high OR rate, superior PFS and OS as compared to fludarabine and cyclophosphamide regimen;
- a direct relationship between the dose of rituximab and the response rate has been reported;
- ofatumumab, as single agent, proved activity in CLL patients with refractory disease;
- ofatumumab, fludarabine and cylophosphamide (O-FC) front-line treatment has been associated with a high complete response (CR) rate;
- the expected grade 3-4 granulocytopenia could led to reduce the dose intensity of study drugs (FC) and increase the infection rate; a schedule combining FC with an increased dose of ofatumumab associated to primary phrophylaxis of granulocytopenia could be associated with an improvement in the CR rate. The purpose of this study is to determine whether we could improve the CR rate of the golden standard treatment for fit patients with CLL , the FCR regimen, with a chemoimmunotherapy including FC combined with an increased dose of the monoclonal antibody ofatumumab, given every other week (FCO2) associated with a primary prophylaxis of granulocytopenia.
Tipo de estudio
Intervencionista
Inscripción (Actual)
80
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Alessandria, Italia
- S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
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Ascoli Piceno, Italia
- Dipartimento Area Medica - Presidio Ospedaliero "C. e G.Mazzoni"
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Asti, Italia
- S.O.C. di Medicina Interna B - Ospedale - Cardinal Massaia di Asti
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Biella, Italia
- ASL12 - Biella Ospedale degli Infermi - Dip. di Medicina e Geriatria - Struttura Complessa di Medicina Interna
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Catanzaro, Italia
- Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
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Ferrara, Italia
- Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna
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Genova, Italia
- RCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente
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Lecce, Italia
- ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
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Messina, Italia
- Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
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Milano, Italia
- Ospedale Niguarda " Ca Granda"
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Novara, Italia
- S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
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Palermo, Italia
- Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
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Parma, Italia
- Cattedra di Ematologia CTMO Università degli Studi di Parma
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Reggio Calabria, Italia
- Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
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Reggio Emilia, Italia
- Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
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Roma, Italia
- U.O.C. Ematologia - Ospedale S.Eugenio
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Roma, Italia
- Padiglione Cesalpino - I piano - Divisione di Ematologia - Ospedale S. Camillo
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Roma, Italia
- Policlinico Umberto I, Hematology Department - Sapienza
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Siena, Italia
- U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
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Terni, Italia
- SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni
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Torino, Italia
- Div. di Ematologia Ospedale "S.Giovanni Battista"
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Udine, Italia
- Clinica Ematologica - Policlinico Universitario
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- B-cell CLL diagnosis by 2008 revised IWCLL criteria.
- Treatment requirement according to the 2008 revised IWCLL criteria.
- No previous treatment.
- Age > 18 year and . 65 years.
- ECOG performance status of 0-1 at study entry and CIRS score .6.
- Adequate renal function (creatinine clearance.60 ml/min estimated using the Cockcroft-Gaultequation) .
- For male and female subjects of childbearing potential, agreement to use effective contraception.
- Signed written informed const according to ICH/EU/GCP and national local laws.
Exclusion Criteria:
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease and/or laboratory abnormality which in the opinion of the investigator may represent a risk for the patient and/or that would prevent the subject from signing the informed consent form.
- Pregnant or lactating females.
- Known positive serology for HIV.
- Positive serology for Hepatitis B (HBV) defined as a positive test for HBsAg and HBV-DNA.
- HCV-RNA positive.
- Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection, tuberculosis and active hepatitis.
- History of tuberculosis within the last five years or recent exposure to tuberculosis equal to or less than 6 months.
- Known presence of alcohol and/or drug abuse.
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to the inclusion in the study, congestive heart failure (NYHA III-IV), arrhythmia unless controlled by therapy.. grade 2 neuropathy; history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
- Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
One or more laboratory abnormalities:
- Calculated creatinine clearance (Cockroft-Gault)<60mL/min.
- Absolute granulocyte count <1500/ƒÊL not disease related.
- Platelet count < 75000/ƒÊL not disease related.
- GOT, GPT, GT, alkaline phosphatase > 1,5 x upper limit of normal value unless due to disease involvement); serum bilirubin >1.5mg/dL, subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones)
- Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
- Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿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 |
|---|---|
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Experimental: Study therapy
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of complete responses.
Periodo de tiempo: After 8 months from study entry.
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The complete response (CR) rate after FCO2 front-line treatment.
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After 8 months from study entry.
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of overall responses.
Periodo de tiempo: After 8 months from study entry.
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Overall Response (OR) rate after FCO2 front-line treatment.
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After 8 months from study entry.
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Number of patients in progression-free survival.
Periodo de tiempo: After 32 months from study entry.
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Progression-free survival (PFS) calculated from the date of first treatment dose - induction phase - until the date of the first documentation of progressive disease or until death (whatever the cause), whichever occurs first.
Patients still alive and known to be progression free will be censored at the moment of last follow-up.
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After 32 months from study entry.
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Number of patients needing a new CLL Treatment.
Periodo de tiempo: After 32 months from study entry.
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Time to a new CLL treatment (TTT) will be calculated from the date of last treatment dose until date of a new treatment received for CLL, where death occurred before the new treatment will be considered as competing risk.
Patients still alive without receiving a new treatment will be censored at the time of the last follow-up.
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After 32 months from study entry.
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Number of patients in overall survival
Periodo de tiempo: After 32 months from study entry.
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Overall survival (OS): defined as the time interval between the date of first treatment dose - induction phase- and the date of death for any cause; patients still alive will be censored at the moment of last follow-up.
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After 32 months from study entry.
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Number of toxic events.
Periodo de tiempo: After 32 months from study entry.
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Toxicity of treatment according the last NCI criteria.
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After 32 months from study entry.
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Outcome of patients according to clinical and biologica variables.
Periodo de tiempo: After 32 months from study entry.
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Outcome of patients (response, PFS OS) according to clinical and biologic variables (age; size of nodes, 2-microglobulin, lymphocyte count, stage, IgVH, p53, FISH, ZAP-70, CD38, FLCs).
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After 32 months from study entry.
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Silla de estudio: Roberto Foà, Pr., Policlinico Umberto I, Hematology Department.
- Director de estudio: Francesca R. Mauro, Policlinico Umberto I, Hematology Department.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Enlaces Útiles
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
5 de noviembre de 2013
Finalización primaria (Actual)
1 de noviembre de 2015
Finalización del estudio (Actual)
1 de octubre de 2018
Fechas de registro del estudio
Enviado por primera vez
4 de enero de 2013
Primero enviado que cumplió con los criterios de control de calidad
4 de enero de 2013
Publicado por primera vez (Estimar)
7 de enero de 2013
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
14 de octubre de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
12 de octubre de 2020
Última verificación
1 de octubre de 2020
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
- Leucemia de células B
- Leucemia
- Leucemia Linfocítica Crónica De Células B
- Leucemia Linfoide
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos, alquilantes
- Agentes alquilantes
- Agonistas mieloablativos
- Ciclofosfamida
- Ofatumumab
- Fludarabina
Otros números de identificación del estudio
- CLL0911
- 2011-005329-27 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
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. .