A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Mantle Cell
• Intervention / Treatment: Drug: Placebo; Drug: Acalabrutinib; Drug: Bendamustine; Drug: Rituximab

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).

• Study Type: Interventional
• Enrollment (Actual): 635
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Research Site
  • Buenos Aires, Argentina, C1431FWO
    • Research Site
  • Buenos Aires, Argentina, C1430EGF
    • Research Site
  • Buenos Aires, Argentina, C1114AAP
    • Research Site
  • Caba, Argentina, C1118AAT
    • Research Site
  • Cordoba, Argentina, 5000
    • Research Site
• Australia
  • Bedford Park, Australia, 5042
    • Research Site
  • Concord, Australia, 2139
    • Research Site
  • Frankston, Australia, 3199
    • Research Site
  • Gosford, Australia, 2250
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  • Heidelberg, Australia, 3084
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  • Herston, Australia, QLD, 4029
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  • Kogarah, Australia, NSW 2217
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  • Murdoch, Australia, 6150
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  • Nedlands, Australia, 6009
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  • Newcastle, Australia, 2298
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  • Southport, Australia, 4215
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  • Sydney, Australia, NSW 2145
    • Research Site
  • Woolloongabba, Australia, 4102
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• Belgium
  • Antwerpen, Belgium, 2060
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  • Ghent, Belgium, 9000
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  • Leuven, Belgium, 3000
    • Research Site
  • Roeselare, Belgium, 8900
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  • Sint-Niklaas, Belgium, 9100
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• Brazil
  • Bela Vista, Brazil, 01321-001
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  • Curitiba, Brazil, 81520-060
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  • Porto Alegre, Brazil, 90035-903
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  • Porto Alegre, Brazil, RS 90610-000
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  • Rio de Janeiro, Brazil, 20231-050
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  • Salvador, Brazil, 41253-190
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  • Sao Paulo, Brazil, 01232-010
    • Research Site
  • Sao Paulo, Brazil, 05652-9000
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  • Sao Paulo, Brazil, 1236030
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  • Sao Paulo, Brazil, 5403
    • Research Site
  • So Paulo, Brazil, 08270-070
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• Canada
  • Edmonton, Canada, T6G 1Z2
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  • Greenfield Park, Canada, J4V 2H1
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  • Halifax, Canada, NS B3H 2Y9
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  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
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  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9,
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    • Toronto, Ontario, Canada, M4N 3M5
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• China
  • Beijing, China, 100036
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  • Changchun, China, 130021
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  • Changsha, China, 410013
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  • Changsha, China, 410008
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  • Chongqing, China, 400037
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  • Dalian, China, 116023
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  • Gongshu District, China, 310022
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  • Haidian District, China, 100191
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  • Harbin, China, 150081
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  • Nanchang, China, 330006
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  • Nanchang, China, 330029
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  • Nanjing, China, 210029
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  • Qingdao, China, 266100
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  • Shanghai, China
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  • Shenyang, China
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  • Suzhou, China, 215006
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  • Tianjian, China, 300020
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  • Tianjin, China
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  • Wenzhou, China, 325000
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  • Wuhan, China, 430079
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  • Wuhan, China, 430030
    • Research Site
  • Wuhou District, China, 610041
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  • Xicheng District, China, 100050
    • Research Site
  • Xuhui District, China, 200032
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  • Xuzhou, China, 221000
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  • Zhengzhou, China, 450008
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  • Zhengzhou City, China, 450000
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• Czechia
  • Brno, Czechia, 625 00
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  • Hradec Kralove, Czechia, 500 05, CZ
    • Research Site
  • Ostrava Poruba, Czechia, 708 52
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  • Pilsen, Czechia, 30460, CZ
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  • Prague, Czechia, 100 34, CZ
    • Research Site
• France
  • Argenteuil, France, 95100
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  • Bobigny, France, 93000
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  • Bordeaux, France, 33076, FR
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  • Le Mans, France, 72000, FR
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  • Limoges, France, 87042
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  • Perigueux, France, 24019
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  • Pessac, France, 33604
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  • Rennes Cedex, France, 35000
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  • Vienne, France, 86000, FR
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• Germany
  • Heidelberg, Germany, 69120, DE
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  • Muenster, Germany, 48149
    • Research Site
  • Munchen, Germany, 81377, DE
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  • Nordrhein-Westfalen, Germany, 52064, DE
    • Research Site
  • Ravensburg, Germany, 88212
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  • Rheinland-Pfalz, Germany, 55131, DE
    • Research Site
  • Ulm, Germany, 89081
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• Greece
  • Athens, Greece, 11525
    • Research Site
  • Athens, Greece, 11527, GR
    • Research Site
  • Athens, Greece, 11528, GR
    • Research Site
  • Ioannina, Greece, 45500, GR
    • Research Site
  • Patras, Greece, 26504
    • Research Site
  • Thessaloniki, Greece, 54007, GR
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  • Thessaloniki, Greece, 57010, GR
    • Research Site
• Hong Kong
  • HKG, Hong Kong, 999077
    • Research Site
  • Pok Fu Lam, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1085
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Győr, Hungary, 9024
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  • Pecs, Hungary, 7624
    • Research Site
  • Szeged, Hungary, 6725
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• Israel
  • Haifa, Israel, 31096
    • Research Site
  • Jerusalem, Israel, 9103102
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  • Petah Tikva, Israel, 494142
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  • Tel Aviv, Israel, 64239
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• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Milano, Italy, 20162
    • Research Site
  • Palermo, Italy, 90146
    • Research Site
  • Parma, Italy
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Reggio Emilia, Italy, 42123
    • Research Site
  • Rozzano, Italy, 20089
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  • Turin, Italy, 10126
    • Research Site
• Japan
  • Fukuoka, Japan, 811-1395
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  • Fukuoka City, Japan, 812-8582
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  • Kobe-shi, Japan, 650-0047
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  • Kyoto-city, Japan, 602-8026
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Nagoya, Japan, 460-0001
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Osaka, Japan, 565-0871
    • Research Site
  • Sapporo-shi, Japan, 003-0006
    • Research Site
  • Sendai-shi, Japan, 980-8574
    • Research Site
  • Shimane, Japan, 693-8501
    • Research Site
  • Tokyo, Japan, 135-8550
    • Research Site
  • Tokyo, Japan, 104-0045
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • Research Site
  • Gyeonggi-do, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 5505
    • Research Site
  • Seoul, Korea, Republic of, 6351
    • Research Site
  • Seoul, Korea, Republic of, 3080
    • Research Site
  • Seoul, Korea, Republic of, 6591
    • Research Site
  • Seoul, Korea, Republic of, 3722
    • Research Site
  • Seoul, Korea, Republic of, 7985
    • Research Site
• Mexico
  • MEX City, Mexico, 2990
    • Research Site
  • Mexico, Mexico, 14080
    • Research Site
  • Monterrey, Mexico
    • Research Site
  • Queretaro, Mexico, 76090
    • Research Site
• New Zealand
  • Dunedin, New Zealand, 9016
    • Research Site
  • Grafton, New Zealand, 1023
    • Research Site
  • Otahuhu, New Zealand, 1640
    • Research Site
• Peru
  • Arequipa, Peru, 5154
    • Research Site
  • Bellavista, Peru
    • Research Site
  • Lima, Peru, 1
    • Research Site
  • Lima, Peru, 34
    • Research Site
• Poland
  • Chorzow, Poland, 41-500
    • Research Site
  • Krakow, Poland, 30-510
    • Research Site
  • Lodz, Poland, 93-510
    • Research Site
  • Lublin, Poland, 20-090
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
  • Warszawa, Poland, 04-141
    • Research Site
  • Warszawa, Poland, 02-106
    • Research Site
  • Warszawa, Poland, 02-776
    • Research Site
  • Woj. Podkarpackie, Poland, 36-200
    • Research Site
  • Wroclaw, Poland, 50-367
    • Research Site
• Romania
  • Brasov, Romania, 50012
    • Research Site
  • Bucharest, Romania, 070131
    • Research Site
  • Cluj-Napoca, Romania, 400124
    • Research Site
  • Iasi, Romania, 700483
    • Research Site
• Russian Federation
  • Pyatigorsk, Russian Federation, 357532
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation, 197341
    • Research Site
  • Syktyvkar, Russian Federation, 167029
    • Research Site
  • Tula, Russian Federation, 300053
    • Research Site
• Spain
  • Badalona, Spain, 8916
    • Research Site
  • Barcelona, Spain, 8035
    • Research Site
  • Barcelona, Spain, 08041
    • Research Site
  • Barcelona, Spain, 8907
    • Research Site
  • Barcelona, Spain, 8003
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Sevilla, Spain
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan, 100
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Research Site
  • Chernihiv, Ukraine, 14029
    • Research Site
  • Dnipropetrovsk, Ukraine, 49102
    • Research Site
  • Kiev, Ukraine, 3022
    • Research Site
  • Lviv, Ukraine, 79044
    • Research Site
  • Zhytomir, Ukraine, 10002
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Research Site
  • California
    • Downey, California, United States, 90241
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Tallahassee, Florida, United States, 32308-5304
      • Research Site
    • West Palm Beach, Florida, United States, 33401
      • Research Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Research Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Site
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
    • Morristown, New Jersey, United States, 07960
      • Research Site
  • New York
    • Hawthorne, New York, United States, 10532
      • Research Site
    • Lake Success, New York, United States, 11042
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
    • Greenville, South Carolina, United States, 29615
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78217
      • Research Site
    • Tyler, Texas, United States, 75702
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site
    • Fort Belvoir, Virginia, United States, 22060
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Research Site
    • Seattle, Washington, United States, 98109
      • Research Site
    • Seattle, Washington, United States, 98108
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site
• Vietnam
  • Hanoi, Vietnam
    • Research Site
  • Hanoi, Vietnam, 123
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Research Site
  • Ho Chi Minh City, Vietnam, WARD 7
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Acalabrutinib; Administered orally (PO); Other Names: Calquence; ACP-196; Drug: Bendamustine; Administered intravenously (IV); Other Names: Treanda; Bendeka; Drug: Rituximab; Administered intravenously (IV); Other Names: Rituxan; Rituxan Hycela
Placebo Comparator: 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.	Drug: Placebo; Placebo comparator; Drug: Bendamustine; Administered intravenously (IV); Other Names: Treanda; Bendeka; Drug: Rituximab; Administered intravenously (IV); Other Names: Rituxan; Rituxan Hycela

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2	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.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Defined as the time from the date of randomization until disease progression (assessed by the investigator per the Lugano Classification for NHL) or death from any cause, whichever occurs first.	Up to 6 years
Investigator-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Defined as the proportion of subjects who achieve either partial response (PR) or complete response (CR) as best overall response according to the Lugano Classification for NHL as assessed by investigator.	Up to 6 years
IRC-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Defined as the proportion of subjects who achieve either PR or CR as best overall response according to the Lugano Classification for NHL as assessed by IRC.	Up to 6 years
Overall survival in Arm 1 compared to Arm 2	Defined as the time from randomization until the date of death from any cause.	Up to 6 years
IRC-assessed duration of response per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Defined as the time from the first documentation of CR or PR to disease progression per the Lugano Classification for NHL or death from any cause, whichever occurs first.	Up to 6 years
IRC assessed time to response per the Lugano Classification for NHL in Arm 1 compared to Arm 2	Defined as the time from randomization to the first CR or PR per the Lugano Classification for NHL.	Up to 6 years

Collaborators and Investigators

• Sponsor: Acerta Pharma BV
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Estimated): October 28, 2025
• Study Completion (Estimated): October 28, 2025

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimated): November 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Rituximab; Mantle Cell Lymphoma; Bruton tyrosine kinase inhibitor; Acalabrutinib; Treatment naive; ACE-LY-308; non-Hodgkins Lymphoma; Bendomustine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Bendamustine Hydrochloride; Rituximab; Acalabrutinib
• Other Study ID Numbers: ACE-LY-308; 2015-005220-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No