A Study Being Conducted at Multiple Locations to Compare Safety and Efficacy of Three Different Regimens; (1) High-Dose Lenalidomide; (2) Lenalidomide + Azacitidine; or (3) Azacitidine in Subjects ≥ 65 Years With Newly-Diagnosed Acute Myeloid Leukemia
17 de junio de 2019 actualizado por: Celgene
A Phase 2, Multicenter, Randomized, Open-label, Parallel-group Study of a Lenalidomide (Revlimid®) Regimen or a Sequential Azacitidine (Vidaza®) Plus Lenalidomide (Revlimid®) Regimen Versus an Azacitidine (Vidaza®) Regimen for Therapy of Older Subjects With Newly Diagnosed Acute Myeloid Leukemia
The study aim is to compare safety and efficacy of high-dose lenalidomide regimen, sequential azacitidine and lenalidomide and an azacitidine in persons ≥65 years with newly-diagnosed acute myeloid leukemia (AML).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
On September 11, 2013, randomization into the continuous 50 mg lenalidomide only arm was temporarily suspended based on review of the data from the first 13 participants and a high rate of discontinuation (11/13 participants).
The Data Monitoring Committee assessed the study data on September 20, 2013 and reported no safety concerns.
The high rate of early discontinuation is inconsistent with the treatment duration required for testing the study primary endpoint of survival at one year.
Consequently, Celgene has decided not to reopen the lenalidomide only arm.
Tipo de estudio
Intervencionista
Inscripción (Actual)
88
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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Alberta
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Calgary, Alberta, Canadá, T2N 4N2
- (402) Tom Baker Cancer Centre
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Edmonton, Alberta, Canadá, T6G 1Z1
- (405) University of Alberta Hospital
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Manitoba
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Winnipeg, Manitoba, Canadá, R3E 0V9
- (401) Cancer Care Manitoba
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Nova Scotia
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Halifax, Nova Scotia, Canadá, B3H 2Y9
- (403) Queen Elizabeth II Health Sciences Centre - VG Site
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Ontario
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Ottawa, Ontario, Canadá, K1H 8L6
- (404) The Ottawa Hospital
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Toronto, Ontario, Canadá, M5G 2M9
- (400) Princess Margaret Hospital
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Arizona
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Tucson, Arizona, Estados Unidos, 85724
- (210) University of Arizona Cancer Center
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California
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La Jolla, California, Estados Unidos, 92093-0960
- (180) University of California, San Diego
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Los Angeles, California, Estados Unidos, 90048
- (240) Cedars-Sinai Medical Center
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Orange, California, Estados Unidos, 92868
- (215) Hematology Oncology Medical Group
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Sacramento, California, Estados Unidos, 95857
- (130) UC Davis Medical Center
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San Luis Obispo, California, Estados Unidos, 93401
- (200) Coastal Integrative Cancer Care
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Stanford, California, Estados Unidos, 94305
- (125) University of Stanford
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Colorado
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Aurora, Colorado, Estados Unidos, 80045
- (115) University of Colorado Anschultz Cancer Center
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Florida
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Miami Beach, Florida, Estados Unidos, 33140
- (145) Mount Sinai Comprehensive Cancer Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60612
- (140) Rush University Medical Center
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Kansas
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Westwood, Kansas, Estados Unidos, 66205
- (185) The University of Kansas Cancer Center
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40202
- (175) University Lousiville
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70072
- (195) Tulane University Hospital Tulane Cancer Center
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Minnesota
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Minneapolis, Minnesota, Estados Unidos, 55455
- (235) University of Minnesota
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63110-1093
- (100) Washington University School of Medicine
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Montana
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Billings, Montana, Estados Unidos, 59101
- (150) Billings Clinic
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New York
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New York, New York, Estados Unidos, 10029-65749
- (165) Mount Sinai Medical Center New York
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15224-1791
- (160) The Western Pennsylvania Hospital- Cancer Institute
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South Carolina
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Greenville, South Carolina, Estados Unidos, 29605
- (205) Greenville Hospital System
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South Dakota
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Sioux Falls, South Dakota, Estados Unidos, 57105
- (120) Avera Cancer Institute
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- (230) Tennessee Oncology, PLLC
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Texas
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Dallas, Texas, Estados Unidos, 75390-9179
- (105) University of Texas Southwestern Medical Center Simmons Comprehensive Cancer Center
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San Antonio, Texas, Estados Unidos, 78229
- (155) Cancer Care Centers of South Texas
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
- (135) University of Wisconsin
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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
65 años y mayores (Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Newly diagnosed acute myeloid leukemia (AML), AML with antecedent hematologic disorder or therapy-related AML
- Male or female subjects aged ≥ 65
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- White blood cell (WBC) count ≤ 10 x 10⁹/L at screening
Exclusion Criteria:
- Previous treatment with azacitidine, decitabine, cytarabine or lenalidomide
- Previous cytotoxic or biologic treatment of any kind for AML or prior use of targeted therapy agents.
- Suspected or proven acute promyelocytic leukemia
- Prior bone marrow or stem cell transplantation
- Candidate for allogeneic bone marrow or stem cell transplantation
- AML antecedent hematologic disorder such as chronic myelogenous leukemia or myeloproliferative neoplasms
- Presence of malignant disease within the previous 12 months with exceptions
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: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Lenalidomide in combination with azacitidine
Repeated cycles of azacitidine 75 mg/m^2/day subcutaneous (SC) on Days 1-7 and lenalidomide 50 mg/day by mouth (PO) on Days 8-28 followed by a 14-day break plus best supportive care
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Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Otros nombres:
Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
Otros nombres:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
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Experimental: Lenalidomide - single agent
Lenalidomide 50 mg PO daily for 28 days for the first 2 cycles and lenalidomide 25 mg daily for 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg daily PO plus best supportive care
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Lenalidomide 50 mg PO daily x 28 days for the first 2 cycles then 25 mg PO daily x 28 days for the next 2 cycles followed by continuous 28-day cycles of lenalidomide 10 mg PO daily
Otros nombres:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
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Experimental: Azacitidine-single agent
Repeated cycles of azacitidine 75mg/m^2/day subcutaneous on Days 1-7 followed by a 21-day break plus best supportive care
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Azacitidine at 75 mg/m^2/day subcutaneous on Days 1-7
Otros nombres:
The use of BSC was considered as concomitant treatment and must be documented as concomitant medication. BSC includes, but is not limited to, treatment with Red Blood Celll (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic or antifungal therapy, and nutritional support |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Kaplan Meier Estimates for One Year Survival
Periodo de tiempo: Up to 24 months
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One-year survival rate was defined as all deaths within one year from the date of randomization.
All others censored at the at year 1 or date of discontinuation
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Up to 24 months
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Overall Survival
Periodo de tiempo: From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)
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Overall Survival reported at the end of the study are for those participants who were alive at the end of the study
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From date of randomization until the date of the first documented date of progression or date of death of any cause; the overall median follow-up for survivng participants was 4.1 months (range 0.2 to 54.8 months)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
Periodo de tiempo: Complete Response or Morphologic Incomplete Response data not analyzed.
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Based on IWG response criteria for AML. Complete remission (CR), morphologic complete remission (CR) was defined as < 5% bone marrow blasts, an absolute neutrophil count ≥ 1 x 10^9/L, platelets ≥100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. Morphologic CR with incomplete blood count recovery (CRi) was defined as a morphologic complete remission but the ANC count may be <1 x 10^9/L and/or the platelet count may be <100 x 10^9/L. Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed. |
Complete Response or Morphologic Incomplete Response data not analyzed.
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Duration of Remission (DoR)
Periodo de tiempo: Duration of Remission (DoR) time frame not analyzed.
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Duration of remission was defined as the time from the date of CR or CRi until relapse.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Duration of Remission (DoR) time frame not analyzed.
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Cytogenetic Complete Remission Rate (CRc)
Periodo de tiempo: Cytogenetic Complete Remission timeframe was not analyzed.
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The CRc response category is comprised of the subset of participants who had abnormal cytogenetics at baseline and subsequently achieved CR during treatment in conjunction with a reversion to a normal karyotype.
For the primary definition of CRc, a normal karyotype is defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques.
Cytogenetic complete remission rate (CRc) 1) CR criteria met AND 2) Abnormal karyotype present at baseline AND 3) Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Cytogenetic Complete Remission timeframe was not analyzed.
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Percentage of Participants With an Overall Response Rate (CR +CRi+ PR)
Periodo de tiempo: Overall response rate time frame was not analyzed.
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Morphologic complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a one marrow aspirate with spicules and with at least 200 nucleated cells (there should be no blasts with auer rods) and ANC of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, no transfusions for 1 week prior to each assessment.
No duration of these findings is required for confirmation of this response.
Morphologic complete remission with incomplete blood count recovery was defined as a morphologic complete remission but the ANC may be < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L.
Partial remission was defined as an ANC > 1 x 10^9/L and platelet count ≥ 100 x 10^9/L with a > 50% decrease in the percentage of bone marrow blasts to 5% to 25% (a blast count value of ≤ 5% may also be considered a partial remission if auer rods are present).
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Overall response rate time frame was not analyzed.
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Progression-Free Survival (PFS)
Periodo de tiempo: Progression-Free survival data and time frame was not analyzed.
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PFS is defined as the time from randomization to the first observation of documented disease progression or death from any cause whichever occurred first.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Progression-Free survival data and time frame was not analyzed.
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Event-Free Survival (EFS)
Periodo de tiempo: Event-Free survival time was not analyzed.
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EFS was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after CR or CRi, or death from any cause, whichever occurred first.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Event-Free survival time was not analyzed.
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Relapse-Free Survival (RFS)
Periodo de tiempo: Relapse-Free survival time frame was not analyzed.
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RFS is defined only for subjects that achieve CR and CRi and is measured as the interval from that date to the date of disease relapse, death from any cause, whichever occurs first, censoring at the last visit date for subjects alive in continuous CR/CRi.
Because of a high rate of discontinuation in one of the investigational cohorts, secondary endpoints were not analyzed.
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Relapse-Free survival time frame was not analyzed.
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Percentage of Participants With 30-Day Treatment-Related Mortality
Periodo de tiempo: 30 days
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30-day mortality rate was defined as death from any cause within 30 days after first dose.
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30 days
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Number of Participants With Treatment Emergent Adverse Events (TEAE)
Periodo de tiempo: From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
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TEAEs were defined as those events that started on or after the first day of study drug up until 28 days after the last dose of study drug; Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability; is a congenital anomaly/birth defect; constitutes an important medical event.
Severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); and according to the scale: Grade (Gr) 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
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From the first dose of study drug up to 28 days after the last dose of study drug; up to 15 May 2018
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Number of Participants With a Second Primary Malignancy
Periodo de tiempo: From randomization of the last participant up to a minimum of 4 years following discontinuation
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Second primary malignancies were monitored as events of interest and reported as serious adverse events regardless of the treatment arm the participant was enrolled in.
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From randomization of the last participant up to a minimum of 4 years following discontinuation
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants Alive at One Year
Periodo de tiempo: Up to 12 months
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Defined as the percentage of participants who survived at one year
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Up to 12 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Director de estudio: Robert Gale, MD, Celgene
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.
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)
27 de abril de 2012
Finalización primaria (Actual)
19 de mayo de 2015
Finalización del estudio (Actual)
15 de mayo de 2018
Fechas de registro del estudio
Enviado por primera vez
19 de mayo de 2011
Primero enviado que cumplió con los criterios de control de calidad
20 de mayo de 2011
Publicado por primera vez (Estimar)
24 de mayo de 2011
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
25 de junio de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
17 de junio de 2019
Última verificación
1 de junio de 2019
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Neoplasias por tipo histológico
- Neoplasias
- Leucemia
- Leucemia Mieloide
- Leucemia Mieloide Aguda
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Factores inmunológicos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Lenalidomida
- Azacitidina
Otros números de identificación del estudio
- CC-5013-AML-001
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 Azacitidine
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Ohio State University Comprehensive Cancer CenterMillennium Pharmaceuticals, Inc.; Celgene CorporationTerminadoSíndromes mielodisplásicos | Leucemia | Neoplasias mielodisplásicas/mieloproliferativasEstados Unidos