A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Bendamustine and Rituximab (BR) Alone Versus in Combination With Acalabrutinib (ACP-196) in Subjects With Previously Untreated Mantle Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 635
- 试验地点
- 228
- 主要终点
- Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2
研究概览
简要总结
This study is evaluating the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR in subjects with previously untreated mantle cell lymphoma.
详细描述
To evaluate the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL) in subjects with previously untreated mantle cell lymphoma (MCL).
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, ≥ 65 years of age.
- •Pathologically confirmed MCL, with documentation of a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5) .
- •MCL requiring treatment and for which no prior systemic anticancer therapies have been received.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Agreement to use highly effective forms of contraception during the study and 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest .
排除标准
- •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, or corrected QT interval (QTc) > 480 msec (calculated using Friderica's formula: QT/RR0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
- •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 (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti infective treatment within 2 weeks before first dose of study drug.
- •Concurrent participation in another therapeutic clinical trial.
研究组 & 干预措施
Placebo in combination with bendamustine and rituximab
Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Placebo (Drug)
Acalabrutinib in combination with bendamustine and rituximab
Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Bendamustine (Drug)
Acalabrutinib in combination with bendamustine and rituximab
Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Acalabrutinib (Drug)
Acalabrutinib in combination with bendamustine and rituximab
Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Rituximab (Drug)
Placebo in combination with bendamustine and rituximab
Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Bendamustine (Drug)
Placebo in combination with bendamustine and rituximab
Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days.
干预措施: Rituximab (Drug)
结局指标
主要结局
Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2
时间窗: Up to 6 years
Defined as the time from the date of randomization until disease progression (assessed by the IRC per the Lugano Classification for NHL) or death from any cause, whichever occurs first.
次要结局
- Investigator-assessed progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2(Up to 6 years)
- Investigator-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2(Up to 6 years)
- IRC-assessed duration of response per the Lugano Classification for NHL in Arm 1 compared to Arm 2(Up to 6 years)
- Overall survival in Arm 1 compared to Arm 2(Up to 6 years)
- IRC-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2(Up to 6 years)
- IRC assessed time to response per the Lugano Classification for NHL in Arm 1 compared to Arm 2(Up to 6 years)