Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL

Chronic Lymphocytic Leukemia Clinical Trial

— AMPLIFY  

Official title:

A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation (AMPLIFY)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03836261
• Other study ID #: ACE-CL-311
• Secondary ID: D8221C000012018-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 25, 2019
• Est. completion date: January 6, 2027

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL

Description:

This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure. The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.

Other known NCT identifiers

• NCT05211856

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 984
• Est. completion date: January 6, 2027
• Est. primary completion date: January 6, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Men and women =18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
• Active disease per IWCLL 2018 criteria that requires treatment.
• Participants must use highly effective birth control throughout the study.

Exclusion Criteria:

• Any prior CLL-specific therapies.
• Detected del(17p) or TP53 mutation.
• Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
• History of confirmed progressive multifocal leukoencephalopathy (PML).
• Received any investigational drug within 30 days before first dose of study drug.
• Major surgical procedure within 30 days before the first dose of study drug.
• Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
• Received a live virus vaccination within 28 days of first dose of study drug.
• Known history of infection with human immunodeficiency virus (HIV).
• Serologic status reflecting active hepatitis B or C infection.
• History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
• Known bleeding disorders.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• Female participants must not be breastfeeding or pregnant.
• Concurrent participation in another therapeutic clinical trial.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Acalabrutinib
Acalabrutinib,
• Venetoclax
Venetoclax
• Chemoimmunotherapy
fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
• Obinutuzumab
Obinutuzumab

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Capital Federal
Argentina	Research Site	Córdoba
Australia	Research Site	Adelaide
Australia	Research Site	Darlinghurst
Australia	Research Site	Heidelberg
Australia	Research Site	Kogarah
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	Waratah
Australia	Research Site	Woolloongabba
Austria	Research Site	Krems
Austria	Research Site	Salzburg
Austria	Research Site	Vienna
Brazil	Research Site	Goiania
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Vratsa
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shengyang
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Urumchi
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xian
China	Research Site	Zhengzhou
China	Research Site	Zhengzhou
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Olomouc
Czechia	Research Site	Ostrava
Czechia	Research Site	Plzen
Czechia	Research Site	Praha
Denmark	Research Site	Aarhus
Denmark	Research Site	Copenhagen
Denmark	Research Site	Roskilde
France	Research Site	Montpellier Cedex 5
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris Cedex 10
France	Research Site	Rennes Cedex 9
France	Research Site	Rouen Cedex 1
France	Research Site	Toulouse Cedex 9
France	Research Site	Villejuif
Germany	Research Site	Paderborn
Germany	Research Site	Würzburg
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Kaposvár
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tiqva
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Hashomer
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Novara
Italy	Research Site	Ravenna
Italy	Research Site	Torino
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Almere
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Breda
Netherlands	Research Site	Den Bosch
Poland	Research Site	Brzozów
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdynia
Poland	Research Site	Krakow
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Sochi
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	Tula
Russian Federation	Research Site	Volgograd
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Slovakia	Research Site	Bratislava
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
South Africa	Research Site	Randburg
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Salamanca
Spain	Research Site	Santander
Spain	Research Site	Valencia
Sweden	Research Site	Göteborg
Sweden	Research Site	Örebro
Sweden	Research Site	Uppsala
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan City
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Izmir
Turkey	Research Site	Kurupelit
Turkey	Research Site	Talas
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Canterbury
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Canton	Ohio
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Fort Sam Houston	Texas
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New York	New York
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Redondo Beach	California
United States	Research Site	Spokane	Washington
United States	Research Site	Tacoma	Washington
United States	Research Site	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Acerta Pharma BV	AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Saudi Arabia,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS	Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria	6 years
Secondary	To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS	PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment	6 years
Secondary	To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.	PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment	6 years