A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation (AMPLIFY)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 984
- 试验地点
- 1
- 主要终点
- To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL
详细描述
This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure.
The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ≥18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
- •Active disease per IWCLL 2018 criteria that requires treatment.
- •Participants must use highly effective birth control throughout the study.
排除标准
- •Any prior CLL-specific therapies.
- •Detected del(17p) or TP53 mutation.
- •Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
- •History of confirmed progressive multifocal leukoencephalopathy (PML).
- •Received any investigational drug within 30 days before first dose of study drug.
- •Major surgical procedure within 30 days before the first dose of study drug.
- •Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- •Received a live virus vaccination within 28 days of first dose of study drug.
- •Known history of infection with human immunodeficiency virus (HIV).
- •Serologic status reflecting active hepatitis B or C infection.
- •History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
- •History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
- •Known bleeding disorders.
- •Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- •Female participants must not be breastfeeding or pregnant.
- •Concurrent participation in another therapeutic clinical trial.
研究组 & 干预措施
Acalabrutinib, Venetoclax
Acalabrutinib in combination with Venetoclax
干预措施: Acalabrutinib (Drug)
Acalabrutinib, Venetoclax
Acalabrutinib in combination with Venetoclax
干预措施: Venetoclax (Drug)
Acalabrutinib, Venetoclax, Obinutuzumab
Acalabrutinib in combination with Venetoclax with Obinutuzumab
干预措施: Acalabrutinib (Drug)
Acalabrutinib, Venetoclax, Obinutuzumab
Acalabrutinib in combination with Venetoclax with Obinutuzumab
干预措施: Venetoclax (Drug)
Acalabrutinib, Venetoclax, Obinutuzumab
Acalabrutinib in combination with Venetoclax with Obinutuzumab
干预措施: Obinutuzumab (Drug)
Chemoimmunotherapy
Chemoimmunotherapy
FCR: Fludarabine, Cyclophosphamide and Rituximab
BR: Bendamustine and Rituximab
干预措施: Chemoimmunotherapy (Drug)
结局指标
主要结局
To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS
时间窗: 6 years
Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria
次要结局
- To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.(6 years)
- To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS(6 years)