Um estudo para avaliar o efeito de Venetoclax em participantes que recebem um inibidor covalente de tirosina quinase de Bruton (cBTKi) para leucemia linfocítica crônica de primeira linha (1L CLL) para obter remissões profundas e duráveis para permitir o período sem tratamento (BRAVE)
Ensaio clínico multicêntrico de fase II, aberto, prospectivo, de braço único, para avaliar se a adição de Venetoclax a pacientes em uso de BTKi covalente para 1L de LLC pode alcançar remissões profundas e duráveis (por UMRD 10 ^ -4) para permitir o período sem tratamento
The main purpose of the study is to evaluate if adding venetoclax to participants receiving cBTKi for the 1L CLL can achieve deep durable remissions of undetectable measurable residual disease [uMRD < or 10^-4 in peripheral blood (PB)] by end of combination treatment (EOCT) to allow off-treatment period.
The acronym BRAVE stands for Btki Responders to Achieve deep remission (or off-treatment periods) with VEnetoclax.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Arkansas
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Springdale, Arkansas, Estados Unidos, 72762
- Highlands Oncology Group
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Colorado
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Aurora, Colorado, Estados Unidos, 80012-5405
- Rocky Mountain Cancer Centers (Aurora) - USOR
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Florida
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Jacksonville, Florida, Estados Unidos, 32256-6932
- Cancer Specialists of North Florida
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Indiana
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Fort Wayne, Indiana, Estados Unidos, 46804
- Fort Wayne Medical Oncology and Hematology, Inc
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Iowa
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Des Moines, Iowa, Estados Unidos, 50314-3030
- Mission Blood and Cancer - MercyOne Cancer Center
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Maryland
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Bethesda, Maryland, Estados Unidos, 20817-1915
- American Oncology Partners of Maryland, PA
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215-5418
- Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center
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Nebraska
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Grand Island, Nebraska, Estados Unidos, 68803
- Nebraska Cancer Specialists St Francis - Grand Island
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Omaha, Nebraska, Estados Unidos, 68130-2042
- Nebraska Cancer Specialists
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New Jersey
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East Brunswick, New Jersey, Estados Unidos, 08816-4096
- Astera Cancer Care East Brunswick
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New Mexico
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Farmington, New Mexico, Estados Unidos, 87401
- San Juan Oncology Associates, PC
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45236-2725
- Oncology Hematology Care Inc - Cincinnati - USOR
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University
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Oregon
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Eugene, Oregon, Estados Unidos, 97401-6043
- Willamette Valley Cancer Institute and Research Center
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Medford, Oregon, Estados Unidos, 97504-8332
- Asante Rogue Regional Medical Center
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Tennessee
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Chattanooga, Tennessee, Estados Unidos, 37404
- Tennessee Oncology, PLLC - Chattanooga
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Nashville, Tennessee, Estados Unidos, 37203
- Tennessee Oncology - Midtown
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Texas
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Houston, Texas, Estados Unidos, 77030
- MD Anderson Cancer Center
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Tyler, Texas, Estados Unidos, 75702
- Texas Oncology- Northeast Texas
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Wisconsin
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Diagnosed with CLL and currently receiving a stable dose of cBTKi (i.e., ibrutinib, acalabrutinib, or zanubrutinib) for at least 6 months for 1L treatment with a response of at least a PR per iwCLL criteria
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 2
- Adequate renal and liver function
Exclusion Criteria:
- Prior B-cell lymphoma (Bcl-2) inhibitor therapy
- Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening
- Progressive or stable disease on cBTKi
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
- History of cardiomyopathy
- Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
- Clinically significant cardiovascular disease
- Active bleeding or history of bleeding diathesis
- Pregnant women and nursing mothers
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Venetoclax Added to cBTKi (Commercially Prescribed)
Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (< 10^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label. |
Venetoclax tablets will be administered as per the schedule specified in the arm.
Outros nomes:
Commercially available cBTKi (ibrutinib or acalabrutinib, or zanubrutinib) will be administered in accordance with its prescribing label. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
uMRD4 Rate at EOCT
Prazo: Cycle 12 Day 28 (Cycle length= 28 Days)
|
uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10^-4) from PB. |
Cycle 12 Day 28 (Cycle length= 28 Days)
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
Prazo: Up to approximately 12 months
|
Complete response (CR)/complete response with incomplete recovery of the bone marrow (CRi) rate is defined as the percentage of participants with a CR or CRi at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
PR Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 12 months
|
PR rate is defined as the percentage of participants with a PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 12 months
|
ORR is defined as the percentage of participants with a CR/CRi or PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: Up to approximately 13 months
|
AE and SAEs will be collected as part of this study at baseline and every clinical visit, until 30 days after the final dose of study treatment. |
Up to approximately 13 months
|
|
Number of Participants Who Withdrew Prematurely from the Study
Prazo: Up to approximately 12 months
|
Participants who discontinued treatment before Cycle 12 Day 28 (cycle length= 28 days). |
Up to approximately 12 months
|
|
Overall Survival (OS)
Prazo: Up to approximately 48 months
|
OS is defined as the time from the first study treatment to death from any cause. |
Up to approximately 48 months
|
|
Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 48 months
|
PFS is defined as the time from the first study treatment to the first occurrence of disease progression (PD) or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 48 months
|
EFS is defined as the time from the first study treatment to the first occurrence of PD, anti-leukemic treatment subsequent to the study treatment, or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR/CRi or PR) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines
Prazo: Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR or CRi ) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Time to Next CLL Treatment (TTNT)
Prazo: Up to approximately 12 months
|
TTNT is defined as the time from the first study treatment to the start of anti-leukemic treatment subsequent to the study treatment or death, whichever occurs first. |
Up to approximately 12 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Clinical Trials, Hoffmann-La Roche
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Processos Patológicos
- Neoplasias
- Doença crônica
- Atributos da doença
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Doenças Hematológicas
- Doenças Linfáticas
- Distúrbios Linfoproliferativos
- Distúrbios imunoproliferativos
- Leucemia de Células B
- Leucemia Linfóide
- Leucemia
- Condições Patológicas, Sinais e Sintomas
- Doenças hemic e linfáticas
- Leucemia Linfocítica Crônica de Células B
- Venetoclax
Outros números de identificação do estudo
- ML45219
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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