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 junho de 2019 atualizado 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).
Visão geral do estudo
Status
Concluído
Intervenção / Tratamento
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
88
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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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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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
65 anos e mais velhos (Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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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
Outros nomes:
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
Outros nomes:
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
Outros nomes:
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
Outros nomes:
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 |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Kaplan Meier Estimates for One Year Survival
Prazo: 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
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of Participants With a Complete Response or Morphologic Incomplete Response.
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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.
|
Progression-Free survival data and time frame was not analyzed.
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Event-Free Survival (EFS)
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of Participants Alive at One Year
Prazo: Up to 12 months
|
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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Robert Gale, MD, Celgene
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
27 de abril de 2012
Conclusão Primária (Real)
19 de maio de 2015
Conclusão do estudo (Real)
15 de maio de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
19 de maio de 2011
Enviado pela primeira vez que atendeu aos critérios de CQ
20 de maio de 2011
Primeira postagem (Estimativa)
24 de maio de 2011
Atualizações de registro de estudo
Última Atualização Postada (Real)
25 de junho de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
17 de junho de 2019
Última verificação
1 de junho de 2019
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Neoplasias por Tipo Histológico
- Neoplasias
- Leucemia
- Leucemia Mieloide
- Leucemia Mieloide Aguda
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Antimetabólitos, Antineoplásicos
- Antimetabólitos
- Agentes Antineoplásicos
- Fatores imunológicos
- Inibidores de angiogênese
- Agentes Moduladores da Angiogênese
- Substâncias de crescimento
- Inibidores de crescimento
- Lenalidomida
- Azacitidina
Outros números de identificação do estudo
- CC-5013-AML-001
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .