A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)

Diffuse Large B-Cell Lymphoma Clinical Trial

— ESCALADE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04529772
• Other study ID #: D8227C00001
• Secondary ID: 2019-001755-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 8, 2020
• Est. completion date: February 5, 2027

Study information

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

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 611
• Est. completion date: February 5, 2027
• Est. primary completion date: February 5, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• acalabrutinib
Investigational Product
• placebo
Placebo comparator
• Prednisone
Investigational Product
• Rituximab
Investigational Product
• Cyclophosphamide
Investigational Product
• Vincristine
Investigational Product
• Doxorubicin
Investigational Product

Locations

Country	Name	City	State
Australia	Research Site	Adelaide
Australia	Research Site	Camperdown
Australia	Research Site	Clayton
Australia	Research Site	Darlinghurst
Australia	Research Site	Heidelberg
Australia	Research Site	Hobart
Australia	Research Site	Kogarah
Australia	Research Site	Liverpool
Australia	Research Site	Nedlands
Australia	Research Site	Westmead
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wels
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brugge
Belgium	Research Site	La Louvière
Brazil	Research Site	Curitiba
Brazil	Research Site	Florianopolis
Brazil	Research Site	Goiania
Brazil	Research Site	Passo Fundo
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Lévis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa
Canada	Research Site	Quebec
Canada	Research Site	Toronto	CA
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Winnipeg	Manitoba
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Jinan
China	Research Site	Luoyang
China	Research Site	Nanchang
China	Research Site	Nanning
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Shijiazhuang
China	Research Site	Suzhou
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xiamen
China	Research Site	Zhengzhou
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Ostrava - Poruba
Czechia	Research Site	Plzen
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 2
France	Research Site	Brest
France	Research Site	Caen Cedex 9
France	Research Site	Marseille cedex 5
France	Research Site	Montpellier
France	Research Site	Nantes
France	Research Site	Pessac
France	Research Site	Pierre Benite
France	Research Site	Rennes Cedex 9
France	Research Site	Toulouse
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Homburg
Germany	Research Site	Neumünster
India	Research Site	Bangalore
India	Research Site	Delhi
India	Research Site	Kochi
India	Research Site	Mumbai
India	Research Site	Nashik
India	Research Site	Pune
Israel	Research Site	Afula
Israel	Research Site	Ashdod
Israel	Research Site	Beer Sheba
Israel	Research Site	Haifa
Israel	Research Site	Haifa
Israel	Research Site	Haifa
Israel	Research Site	Holon
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Nahariya
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel Aviv
Israel	Research Site	Zerifin
Italy	Research Site	Bari
Italy	Research Site	Bergamo
Italy	Research Site	Bologna
Italy	Research Site	Firenze
Italy	Research Site	Genova
Italy	Research Site	Meldola
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Novara
Italy	Research Site	Palermo
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Ravenna
Italy	Research Site	Reggio Emilia
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Siena
Italy	Research Site	Torino
Italy	Research Site	Tricase
Italy	Research Site	Venezia
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kahoku-gun
Japan	Research Site	Kashiwa
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kyoto-city
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shimotsuke-shi
Japan	Research Site	Tsu-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Jeonju-si
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	Suwon-si
Mexico	Research Site	Chihuahua
Mexico	Research Site	Monterrey
Poland	Research Site	Gdansk
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Portugal	Research Site	Braga
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Matosinhos
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Vila Nova de Gaia
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	St. Petersburg
Spain	Research Site	Alcalá De Henares
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Gijón
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Palma
Spain	Research Site	Pamplona
Spain	Research Site	Pozuelo de Alarcón
Spain	Research Site	Salamanca
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei 112
Taiwan	Research Site	Taoyuan City
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Balcova
Turkey	Research Site	Edirne
Turkey	Research Site	Izmir
Turkey	Research Site	Kayseri
Turkey	Research Site	Mersin
Turkey	Research Site	Samsun
Turkey	Research Site	Trabzon
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Khmelnytskyi
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Mykolayiv
Ukraine	Research Site	Zaporizhzhia
United States	Research Site	Albany	New York
United States	Research Site	Aurora	Colorado
United States	Research Site	Baltimore	Maryland
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Des Moines	Iowa
United States	Research Site	Eugene	Oregon
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Sam Houston	Texas
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Irvine	California
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Lubbock	Texas
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Norwich	Connecticut
United States	Research Site	Orlando	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Salem	Virginia
United States	Research Site	Stony Brook	New York
United States	Research Site	Tallahassee	Florida
United States	Research Site	Tucson	Arizona
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Wichita	Kansas
United States	Research Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Acerta Pharma BV	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B		at every single visit up to 60 months
Secondary	Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B		at every single visit up to 60 months
Secondary	Overall survival in Arm A compared to Arm B		at every single visit up to 60 months
Secondary	Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification for NHL		at every single visit up to 60 months