Clinical trial NCT02972840: A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lymphoma, Mantle Cell
Keywords: Bruton tyrosine kinase inhibitor
Acalabrutinib
Mantle Cell Lymphoma
ACE-LY-308
Treatment naive
non-Hodgkins Lymphoma
Bendomustine
Rituximab
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2016-11-25
Enrollment: 635
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* 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 ≤ 2.
* 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 .

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
Secondary outcomes:
measure: Investigator-assessed progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
measure: Investigator-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
measure: IRC-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
measure: Overall survival in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
measure: IRC-assessed duration of response per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
measure: IRC assessed time to response per the Lugano Classification for NHL in Arm 1 compared to Arm 2
timeFrame: Up to 6 years
Other outcomes:
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country: Russian Federation
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country: Russian Federation
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country: Spain
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city: Barcelona
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city: Taipei
country: Taiwan
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city: Taoyuan
country: Taiwan
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city: Cherkasy
country: Ukraine
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city: Chernihiv
country: Ukraine
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city: Dnipropetrovsk
country: Ukraine
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city: Kiev
country: Ukraine
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city: Lviv
country: Ukraine
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city: Zhytomir
country: Ukraine
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city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh City
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: