A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects ≤75 Years with Previously Untreated Non-Germinal Center Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 7
- 主要终点
- Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B
研究概览
简要总结
This study will evaluate the safety and efficacy of the small-molecule BTK inhibitor acalabrutinib in combination with R-CHOP, versus placebo plus R-CHOP, in adult subjects ≤65 years of age with previously untreated non-GCB DLBCL. The design and conduct of this study are supported by an understanding of the natural history and current therapies for subjects with DLBCL; knowledge of the activity and safety of the B-cell receptor (BCR) inhibitors (i.e., ibrutinib) in subjects with B-cell malignancies; and the available nonclinical and clinical information regarding acalabrutinib.
Primary objective of this study is to evaluate if the addition of acalabrutinib to R-CHOP prolongs PFS, as compared with placebo plus R-CHOP alone in subjects ≤65 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP, based on investigator assessed response.
This is a global multicenter study with approximately 250 sites. Subjects will be randomized to study treatment only after GEP-confirmation of non-GCB DLBCL. Approximately 600 subjects with previously untreated non-GBC DLBCL will be randomized in a 1:1 ratio into 2 treatment arms (n=300 subjects each) to receive either acalabrutinib in combination with R-CHOP (Arm A), or placebo in combination with R-CHOP (Arm B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Men and women, age ≥18 and ≤75 years Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review.
- •No prior treatment for DLBCL Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •International Prognostic Index (IPI) score of 2 to 5 Disease Stage II to IV by the Ann Arbor Classification Adequate organ and marrow function Agreement to use highly effective forms of contraception during the study and 12 months after the last dose of rituximab.
排除标准
- •Evidence of severe or uncontrolled systemic diseases Known history of a bleeding diathesis (i.e., haemophilia, von Willebrand disease) History of stroke or intracranial haemorrhage in preceding 6 months.
- •Known CNS lymphoma or leptomeningeal disease Known primary mediastinal lymphoma Known High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements Prior history of indolent lymphoma or CLL History of or ongoing confirmed progressive multifocal leukoencephalopathy Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- •Uncontrolled active systemic fungal, bacterial, viral, or other infection Prior anthracycline use ≥150 mg/m2 Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- •Requires treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
- •Patients receiving proton pump inhibitors who switch to short-acting H2-receptor antagonists or antacids are eligible for enrolment into this study.
结局指标
主要结局
Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B
时间窗: At every single visit up to 60 months
次要结局
- Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B(Overall survival in Arm A compared to Arm B)