Clinical trial NCT04529772: A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)
Official title: 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-GCB DLBCL
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Untreated Non-Germinal Center Diffuse Large B-Cell Lymphoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Acalabrutinib
Calquence
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2020-08-28
Enrollment: 611
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind Randomised Placebo-controlled Study
Primary purpose: TREATMENT

Brief summary: Phase 3 randomized, double-blind, placebo-controlled, study assessing the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) vs placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma.

Detailed description: Phase 3 randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as compared with placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma (activated B-cell (ABC) and unclassified).

Eligibility criteria: Inclusion Criteria:

* 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 ≤ 2.
* International Prognostic Index (IPI) score of 1 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

Exclusion Criteria:

* 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 PML
* 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

Primary outcomes:
measure: Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B
timeFrame: at every single visit up to 60 months
Secondary outcomes:
measure: Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B
timeFrame: at every single visit up to 60 months
measure: Overall survival in Arm A compared to Arm B
timeFrame: at every single visit up to 60 months
measure: Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification for NHL
timeFrame: at every single visit up to 60 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Irvine
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Norwich
country: United States
facility: Research Site
state: Connecticut
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Tallahassee
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Grand Rapids
country: United States
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state: Michigan
city: Minneapolis
country: United States
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state: Minnesota
city: Saint Louis
country: United States
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state: Missouri
city: Albany
country: United States
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state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Eugene
country: United States
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state: Oregon
city: Portland
country: United States
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state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Nashville
country: United States
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state: Tennessee
city: Fort Sam Houston
country: United States
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state: Texas
city: Lubbock
country: United States
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state: Texas
city: Salem
country: United States
facility: Research Site
state: Virginia
city: Adelaide
country: Australia
facility: Research Site
city: Camperdown
country: Australia
facility: Research Site
city: Clayton
country: Australia
facility: Research Site
city: Darlinghurst
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Hobart
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: Liverpool
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Salzburg
country: Austria
facility: Research Site
city: Wels
country: Austria
facility: Research Site
city: Antwerpen
country: Belgium
facility: Research Site
city: Brugge
country: Belgium
facility: Research Site
city: La Louvière
country: Belgium
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Florianopolis
country: Brazil
facility: Research Site
city: Goiania
country: Brazil
facility: Research Site
city: Passo Fundo
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Toronto
country: Canada
facility: Research Site
state: CA
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: London
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Lévis
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Ottawa
country: Canada
facility: Research Site
city: Quebec
country: Canada
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Ostrava - Poruba
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Caen Cedex 9
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Pierre Benite
country: France
facility: Research Site
city: Rennes Cedex 9
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Homburg
country: Germany
facility: Research Site
city: Neumünster
country: Germany
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Delhi
country: India
facility: Research Site
city: Kochi
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: Nashik
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Afula
country: Israel
facility: Research Site
city: Ashdod
country: Israel
facility: Research Site
city: Beer Sheba
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Zerifin
country: Israel
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Novara
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Tricase
country: Italy
facility: Research Site
city: Venezia
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Kahoku-gun
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kyoto-city
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagasaki-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shimotsuke-shi
country: Japan
facility: Research Site
city: Tsu-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Braga
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Matosinhos
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Vila Nova de Gaia
country: Portugal
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Alcalá De Henares
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Gijón
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Palma
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Pozuelo de Alarcón
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei 112
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Balcova
country: Turkey
facility: Research Site
city: Edirne
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kayseri
country: Turkey
facility: Research Site
city: Mersin
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Trabzon
country: Turkey
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Khmelnytskyi
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Mykolayiv
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
Study officials:
References: