Chemotherapy for Participants With Lymphoma
23 de julio de 2020 actualizado por: Eli Lilly and Company
An Open-label, Single Arm, Phase 2 Study of Rituximab, Gemcitabine and Oxaliplatin Plus Enzastaurin as Treatment for Patients With Relapsed Diffuse Large B-Cell Lymphoma
The primary purpose of this study is to help answer the following research questions:
- To assess whether Enzastaurin combined with rituximab, gemcitabine and oxaliplatin (R-GEMOX) can help participants with Diffuse Large B-Cell Lymphoma (DLBCL) remain free from disease and thus live longer.
- To assess for any side effects that might be associated with enzastaurin and R-GEMOX .
- To look at the characteristics and levels of certain genes and proteins to learn more about DLBCL and how enzastaurin works in the body.
- To look at the level of enzastaurin in the body and how long it remains.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
68
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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Berlin, Alemania, D-12203
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Bremen, Alemania, 28205
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Essen, Alemania, D-4600
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Hamburg, Alemania, 20099
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Kassel, Alemania, 34125
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Kiel, Alemania, 24116
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Mainz, Alemania, 55131
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Moscow, Federación Rusa, 125167
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Saint Petersburg, Federación Rusa, 198255
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Creteil, Francia, 94010
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Dijon, Francia, 21079
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Lille, Francia, 59037
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Nice, Francia, 06202
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Nimes, Francia, 30029
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Paris, Francia, 75475
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Pessac, Francia, 33604
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Pierre Benite, Francia, 69495
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Rouen, Francia, 76038
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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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
60 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Diagnosis of DLBCL or transformed (cluster differentiation 20 [CD20]+) indolent lymphoma
- Relapsed/progressed after response obtained in 1st- or 2nd-line treatment, or participants who have not progressed after stable disease (SD) obtained in 1st- or 2nd-line.
- Measurable disease (lymph node greater than 1.5 cm)
- Adequate organ function
- Greater than or equal to 60 years or less than 60 (but greater than or equal to 18 years) who are not eligible for high-dose chemotherapy high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT)
Exclusion Criteria:
- Prior Allogeneic transplantation
- More than 2 prior anticancer treatment regimens
- Pregnant or breastfeeding
- Human-immunodeficiency-virus (HIV)associated lymphomas
- Brain metastases
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: Enzastaurin + Gemcitabine Rituximab Oxaliplatin (R-GEMOX)
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1125 mg loading dose then 500 mg, oral, daily, until disease progression or 3 years
Otros nombres:
1000 mg/m², IV, once, every two weeks, four to eight 2 week cycles
Otros nombres:
375 mg/m², IV, once every 2 weeks, four to eight 2 week cycles
100 mg/m², IV, once every two weeks, four to eight 2 week cycles
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Percent of Participants With Progression Free Survival (PFS) After 1 Year Treatment
Periodo de tiempo: First Dose of Study Drug to Measured Progressive Disease or Death from Any Cause at 1 Year
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PFS is defined as the rate at 1 year from the date of first dose of study drug to the first date of measured PD or death from any cause and was determined using the distribution of overall PFS times.
The PFS rate at 1 year was determined using Kaplan-Meier estimates.
For participants not known to have died as of the data cut-off date and who do not have PD, PFS was censored at the date of the last progression-free disease assessment.
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First Dose of Study Drug to Measured Progressive Disease or Death from Any Cause at 1 Year
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Response Rate (ORR) - Percentage of Participants Achieving Complete Response (CR) or Complete Response Unconfirmed (CRu) or Partial Response (PR) (Response)
Periodo de tiempo: Baseline to Measured Progressive Disease or Death from Any Cause at End of 4 and 8 Cycles
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Assessment of response was based on the International Workshop to Standardize Response criteria for lymphoma (Cheson et al. 1999).
CR is the complete disappearance of all detectable clinical and radiologic evidence of disease; all lymph nodes and nodal masses must have regressed to normal size (≤1.5 cm in their greatest transverse diameter for nodes >1.5 cm before therapy).CRu is as CR but with 1 or more of the following features: A residual lymph node mass >1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of the greatest diameters (SPD) and/or indeterminate bone marrow with normalization of all biologic abnormalities.
PR is regression of more than 50% (SPD) of all measurable lesions, disappearance of nonmeasurable lesions and no new lesion.
For each response category the number of participants with this response will be divided by the total number of participants treated to achieve the response rate.
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Baseline to Measured Progressive Disease or Death from Any Cause at End of 4 and 8 Cycles
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Percent of Participants With Progression-Free Survival (PFS) After 2 Years and 4 Years of Treatment
Periodo de tiempo: First Dose of Study Drug to Measured Progressive Disease or Death from Any Cause at 2 Years, 4 Years
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PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). PFS rate was defined as the rate of PFS at 2 year from the date of first dose of study drug and was determined using the distribution of overall PFS times. PFS rate was defined as the rate of PFS at 4 year from the date of first dose of study drug and was determined using the distribution of overall PFS times. For participants not known to have died as of the data cut-off date and who did not have PD, PFS was censored at the date of the last progression-free disease assessment. |
First Dose of Study Drug to Measured Progressive Disease or Death from Any Cause at 2 Years, 4 Years
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Percent of Participants With Overall Survival (OS) After 1 Year, 2 Years and 4 Years
Periodo de tiempo: First Dose of Study Drug to Death from Any Cause at 1 Year, 2 Years and 4 Years
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Overall survival was defined as the time from the date of first dose of study drug to the date of death from any cause.
For participants who were not still alive at the time of analysis, survival time was censored at the last contact date.
For participants not known to have died as of the cut-off date for analysis,OS was censored at the last contact date for participants in post-discontinuation.
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First Dose of Study Drug to Death from Any Cause at 1 Year, 2 Years and 4 Years
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Percent of Participants With Event Free Survival (EFS) After 1 Year, 2 Years and 4 Years
Periodo de tiempo: First Dose of Study Drug to Measured PD, or Start of New Lymphoma Treatment or Death from Any Cause at 1 Year, 2 Years and 4 Years
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Event-free survival time was defined as the time from the date of first dose of study drug to the first date of measured PD,or start of a new treatment for the lymphoma, or death from any cause.
For participants not known to have events as of the data cut-off date, EFS was censored at the date of the last tumor assessment.
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First Dose of Study Drug to Measured PD, or Start of New Lymphoma Treatment or Death from Any Cause at 1 Year, 2 Years and 4 Years
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Progression-Free Survival (PFS ) of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Germinal-Center B-cells (GCB) Versus Non-GCB Molecular Subtypes (Assessment of Biomarkers Relevant for Enzastaurin)
Periodo de tiempo: Baseline, Cycles 1-4, End of Study
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PFS based on DLBCL molecular subtypes (GCB vs non-GCB) were determined.
The molecular characterization of germinal center B-cells (GCBs) vs. non-GCBs was analyzed as separate combination immunohistochemistry (IHC) markers based on the Hans algorithms.
Molecular subtype was included as class effect in the analytical models, adjusting for International Prognostic Index (IPI) score.
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Baseline, Cycles 1-4, End of Study
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PFS of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Protein Kinase C Beta 2 (PKCB2) Expression (Assessment of Biomarkers Relevant for Enzastaurin)
Periodo de tiempo: Baseline, Cycles 1-4, End of Study
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Reported PFS was based on PKCB2 protein expression assessed by immunohistochemistry (scored in 10% increments for percent of tumor cells).
Protein expression levels was grouped into high and low in association with the clinical endpoints.
Grouping was based on 1) a pre-specified threshold provided by the pathologist at Cleveland Clinic for the diffuse large B-cell lymphoma (DLBCL)-prognostic markers, and 2) a median cut-point for the enzastaurin-specific markers.
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Baseline, Cycles 1-4, End of Study
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Pharmacokinetics (PK): Maximum Observed Drug Concentration During a Dosing Interval at Steady State(Cmax,ss) for Total Analyte [Characterization of Pharmacokinetics of Enzastaurin and Its Metabolites]
Periodo de tiempo: Day 2 of Cycle 2: Predose;1-2 Hours(H);3-4 h;5-6 h;7-8 H Postdose
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Cmax,ss is defined as the maximum observed drug concentration during a dosing interval at steady state.
Non-Compartmental Pharmacokinetic Parameters for Total Analyte (Enzastaurin + LSN326020).
LSN326020 is Enzastaurin's major active metabolite.
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Day 2 of Cycle 2: Predose;1-2 Hours(H);3-4 h;5-6 h;7-8 H Postdose
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PK: Area Under the Concentration vs. Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) for Total Analyte
Periodo de tiempo: Day 2 of Cycle 2: Predose;1-2 hours(h);3-4 h;5-6 h;7-8 h Postdose
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AUCτ,ss is defined as the area under the concentration versus time curve during 1 dosing interval at steady state.
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Day 2 of Cycle 2: Predose;1-2 hours(h);3-4 h;5-6 h;7-8 h Postdose
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Percent of Participants With Disease-Free Survival (DFS) at 1 Year, 2 Years and 4 Years
Periodo de tiempo: First Dose of Study Drug to Relapse after CR or CRu or Death from any Cause at 1 Year, 2 Years and 4 Years
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DFS was calculated as the duration from date of first dose of study drug to the date of first relapse event after CR or CRu or death from any cause.
Participants who have not experienced an event at the time of analysis were censored at the most recent date of disease assessment.
Events are relapse after a CR or CRu.
Related death or death from unknown cause was considered as an event.
Unrelated death was not considered as an event and the participant was censored at the time of death for this analysis.
Unrelated death was defined as death from a cause not related to the lymphoma, any examination done for the lymphoma, or any treatment of the lymphoma.
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First Dose of Study Drug to Relapse after CR or CRu or Death from any Cause at 1 Year, 2 Years and 4 Years
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Duration of Tumor Response (DOR)
Periodo de tiempo: Time from Observed CR and CRu or PR (Up to 4 Years)
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Duration of tumor response was defined as the time from the date when the measurement criteria were met for CR and CRu or PR (whichever status was recorded first) until the date of first observation of objective disease progression.
For responding patients who died without objective PD (including death from study disease), duration of response was censored at the date of the last objective progression-free disease assessment.
For responding patients not known to have died as of the data cut-off date and who do not have objective PD, duration of response was censored at the date of the last objective progression-free disease assessment.
For responding patients who received subsequent systemic anticancer therapy (after discontinuation from the study chemotherapy) prior to objectively determined disease progression, duration of response was censored at the date of the last objective progression-free disease assessment prior to post-discontinuation therapy.
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Time from Observed CR and CRu or PR (Up to 4 Years)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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
1 de febrero de 2007
Finalización primaria (Actual)
1 de noviembre de 2009
Finalización del estudio (Actual)
1 de noviembre de 2012
Fechas de registro del estudio
Enviado por primera vez
16 de febrero de 2007
Primero enviado que cumplió con los criterios de control de calidad
16 de febrero de 2007
Publicado por primera vez (Estimar)
19 de febrero de 2007
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
6 de agosto de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
23 de julio de 2020
Última verificación
1 de julio de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Enfermedades linfáticas
- Trastornos inmunoproliferativos
- Linfoma No Hodgkin
- Linfoma de células B
- Linfoma
- Linfoma de células B grandes, difuso
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes antineoplásicos inmunológicos
- Gemcitabina
- Oxaliplatino
- Rituximab
Otros números de identificación del estudio
- 9819 (Otro identificador: Fred Hutch/University of Washington Cancer Consortium)
- H6Q-MC-S013 (Otro identificador: Eli Lilly and Company)
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 enzastaurin
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Eli Lilly and CompanyTerminadoGlioblastoma multiformeAlemania