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

Lymphoma, Mantle Cell Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02972840
• Other study ID #: ACE-LY-308
• Secondary ID: 2015-005220-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 5, 2017
• Est. completion date: October 28, 2025

Study information

• Verified date: June 2024
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 635
• Est. completion date: October 28, 2025
• Est. primary completion date: October 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle Cell
• Lymphoma, Mantle-Cell

Intervention

Drug:
• Acalabrutinib
Administered orally (PO)
• Bendamustine
Administered intravenously (IV)
• Rituximab
Administered intravenously (IV)
• Placebo
Placebo comparator

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Cordoba
Australia	Research Site	Bedford Park
Australia	Research Site	Concord
Australia	Research Site	Frankston
Australia	Research Site	Gosford
Australia	Research Site	Heidelberg
Australia	Research Site	Herston
Australia	Research Site	Kogarah
Australia	Research Site	Murdoch
Australia	Research Site	Nedlands
Australia	Research Site	Newcastle
Australia	Research Site	Southport
Australia	Research Site	Sydney
Australia	Research Site	Woolloongabba
Belgium	Research Site	Antwerpen
Belgium	Research Site	Ghent
Belgium	Research Site	Leuven
Belgium	Research Site	Roeselare
Belgium	Research Site	Sint-Niklaas
Brazil	Research Site	Bela Vista
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	So Paulo
Canada	Research Site	Edmonton
Canada	Research Site	Greenfield Park
Canada	Research Site	Halifax
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Dalian
China	Research Site	Gongshu District
China	Research Site	Haidian District
China	Research Site	Harbin
China	Research Site	Nanchang
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Qingdao
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Suzhou
China	Research Site	Tianjian
China	Research Site	Tianjin
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Wuhou District
China	Research Site	Xicheng District
China	Research Site	Xuhui District
China	Research Site	Xuzhou
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou City
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Ostrava Poruba
Czechia	Research Site	Pilsen
Czechia	Research Site	Prague
France	Research Site	Argenteuil
France	Research Site	Bobigny
France	Research Site	Bordeaux
France	Research Site	Le Mans
France	Research Site	Limoges
France	Research Site	Perigueux
France	Research Site	Pessac
France	Research Site	Rennes Cedex
France	Research Site	Vienne
Germany	Research Site	Heidelberg
Germany	Research Site	Muenster
Germany	Research Site	Munchen
Germany	Research Site	Nordrhein-Westfalen
Germany	Research Site	Ravensburg
Germany	Research Site	Rheinland-Pfalz
Germany	Research Site	Ulm
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Ioannina
Greece	Research Site	Patras
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	HKG
Hong Kong	Research Site	Pok Fu Lam
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Pecs
Hungary	Research Site	Szeged
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Israel	Research Site	Tel Aviv
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Palermo
Italy	Research Site	Parma
Italy	Research Site	Pavia
Italy	Research Site	Reggio Emilia
Italy	Research Site	Rozzano
Italy	Research Site	Turin
Japan	Research Site	Fukuoka
Japan	Research Site	Fukuoka City
Japan	Research Site	Kobe-shi
Japan	Research Site	Kyoto-city
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shimane
Japan	Research Site	Tokyo
Japan	Research Site	Tokyo
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	MEX City
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Queretaro
New Zealand	Research Site	Dunedin
New Zealand	Research Site	Grafton
New Zealand	Research Site	Otahuhu
Peru	Research Site	Arequipa
Peru	Research Site	Bellavista
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Chorzow
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Woj. Podkarpackie
Poland	Research Site	Wroclaw
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Iasi
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Syktyvkar
Russian Federation	Research Site	Tula
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Pamplona
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Chernihiv
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Kiev
Ukraine	Research Site	Lviv
Ukraine	Research Site	Zhytomir
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Downey	California
United States	Research Site	Fort Belvoir	Virginia
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Hawthorne	New York
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Missouri
United States	Research Site	Lake Success	New York
United States	Research Site	Louisville	Kentucky
United States	Research Site	Marietta	Georgia
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Morristown	New Jersey
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Monica	California
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Tallahassee	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	Tyler	Texas
United States	Research Site	Washington	District of Columbia
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Westwood	Kansas
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
Acerta Pharma BV	AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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