Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
AMPLIFY
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)
4 other identifiers
interventional
984
26 countries
162
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2019
Longer than P75 for phase_3
162 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 6, 2019
CompletedFirst Posted
Study publicly available on registry
February 11, 2019
CompletedStudy Start
First participant enrolled
February 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
December 27, 2024
December 1, 2024
7.9 years
February 6, 2019
December 24, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS
6 years
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.
6 years
Study Arms (3)
Acalabrutinib, Venetoclax
EXPERIMENTALAcalabrutinib in combination with Venetoclax
Acalabrutinib, Venetoclax, Obinutuzumab
EXPERIMENTALAcalabrutinib in combination with Venetoclax with Obinutuzumab
Chemoimmunotherapy
ACTIVE COMPARATORChemoimmunotherapy FCR: Fludarabine, Cyclophosphamide and Rituximab BR: Bendamustine and Rituximab
Interventions
Acalabrutinib,
Venetoclax
fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Acerta Pharma BVlead
- AstraZenecacollaborator
Study Sites (170)
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Los Angeles, California, 90095, United States
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Redondo Beach, California, 90277, United States
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Fort Wayne, Indiana, 46804, United States
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Wichita, Kansas, 67214, United States
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Louisville, Kentucky, 40207, United States
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New Orleans, Louisiana, 70056, United States
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Baltimore, Maryland, 21201, United States
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Boston, Massachusetts, 02215, United States
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New York, New York, 10021, United States
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Charlotte, North Carolina, 28204, United States
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Canton, Ohio, 44718, United States
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Pittsburgh, Pennsylvania, 15224, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Fort Sam Houston, Texas, 78234, United States
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Spokane, Washington, 99208, United States
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Tacoma, Washington, 98405, United States
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Buenos Aires, 1114, Argentina
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Buenos Aires, C1426ANZ, Argentina
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Capital Federal, 1118, Argentina
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Córdoba, 5000, Argentina
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Adelaide, 5000, Australia
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Darlinghurst, 2010, Australia
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Heidelberg, 3084, Australia
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Kogarah, 2217, Australia
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Melbourne, 3000, Australia
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Nedlands, 6009, Australia
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Waratah, 2298, Australia
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Woolloongabba, 4102, Australia
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Krems, 3500, Austria
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Salzburg, 5020, Austria
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Vienna, 1140, Austria
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Goiânia, 74605-020, Brazil
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Porto Alegre, 90020-090, Brazil
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Porto Alegre, 90035-003, Brazil
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Porto Alegre, 90110-270, Brazil
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Rio de Janeiro, 20230-130, Brazil
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Rio de Janeiro, 22793-080, Brazil
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São Paulo, 01236-030, Brazil
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São Paulo, 01308-050, Brazil
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São Paulo, 05403-010, Brazil
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Plovdiv, 4000, Bulgaria
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Sofia, 1606, Bulgaria
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Vratsa, 3000, Bulgaria
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Calgary, Alberta, T2N 5G2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Beijing, 100034, China
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Beijing, 100044, China
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Beijing, 100191, China
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Changchun, 130021, China
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Changsha, 410008, China
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Chengdu, 610041, China
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Chongqing, 400037, China
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Guangzhou, 510100, China
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Guangzhou, 510515, China
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Hangzhou, 310003, China
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Nanchang, 330006, China
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Nanjing, 210029, China
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Shenyang, 110001, China
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Shenyang, 110134, China
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Tianjin, 300020, China
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Ürümqi, 830054, China
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Wenzhou, 325000, China
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Wuhan, 430022, China
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Wuhan, 430030, China
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Xi'an, 710061, China
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Zhengzhou, 450008, China
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Zhengzhou, 450052, China
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Brno, 625 00, Czechia
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Hradec Králové, 500 05, Czechia
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Olomouc, 779 00, Czechia
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Ostrava - Poruba, 70852, Czechia
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Plzen - Lochotin, 304 60, Czechia
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Prague, Czechia
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Aarhus, 8200, Denmark
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Copenhagen, 2100, Denmark
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Roskilde, 4000, Denmark
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Montpellier, 34090, France
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Paris, 75013, France
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Paris, 75015, France
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Paris, 75475, France
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Rennes, 35033, France
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Rouen, 76038, France
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Toulouse, 31059, France
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Villejuif, 94800, France
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Paderborn, 33098, Germany
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Würzburg, 97080, Germany
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Budapest, 1083, Hungary
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Budapest, 1125, Hungary
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Debrecen, 4032, Hungary
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Kaposvár, 7400, Hungary
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Haifa, 31999, Israel
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Jerusalem, 91120, Israel
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Jerusalem, Israel
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Petah Tikva, 49100, Israel
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Tel Aviv, 64239, Israel
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Tel Litwinsky, 52620, Israel
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20162, Italy
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Novara, 28100, Italy
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Ravenna, 48121, Italy
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Torino, 10126, Italy
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's-Hertogenbosch, 5223 GZ, Netherlands
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Almere Stad, 1315 RA, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Arnhem, 6815 AD, Netherlands
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Breda, 4818 CK, Netherlands
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Brzozów, 36-200, Poland
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Bydgoszcz, 85-168, Poland
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Gdynia, 81-519, Poland
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Krakow, 30-727, Poland
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Lodz, 93-510, Poland
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Lublin, 20-081, Poland
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Wroclaw, 50-367, Poland
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Wroclaw, 50-556, Poland
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Moscow, 115478, Russia
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Moscow, 125284, Russia
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Saint Petersburg, 191024, Russia
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Saint Petersburg, 197341, Russia
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Saint Petersburg, 197347, Russia
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Samara, 443095, Russia
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Sochi, 354057, Russia
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Tula, 300053, Russia
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Volgograd, 400138, Russia
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Dammam, 31444, Saudi Arabia
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Jeddah, 21423, Saudi Arabia
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Riyadh, 12713, Saudi Arabia
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Bratislava, 83310, Slovakia
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Bloemfontein, 9301, South Africa
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Cape Town, 7925, South Africa
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Pretoria, 0044, South Africa
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Randburg, 2125, South Africa
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Soweto, 2013, South Africa
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Incheon, 21565, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06591, South Korea
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Badalona, 08916, Spain
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Barcelona, 08035, Spain
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Barcelona, 08041, Spain
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Madrid, 28007, Spain
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Madrid, 28031, Spain
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Majadahonda, 28222, Spain
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Salamanca, 37007, Spain
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Santander, 39008, Spain
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Valencia, 46009, Spain
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Gothenburg, 41345, Sweden
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Örebro, 70185, Sweden
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Uppsala, 75185, Sweden
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Kaohsiung City, 833, Taiwan
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Taichung, 404, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 11217, Taiwan
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Taoyuan, 333, Taiwan
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Ankara, 06100, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Izmir, 35340, Turkey (Türkiye)
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Kurupelit, 55139, Turkey (Türkiye)
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Talas, 38280, Turkey (Türkiye)
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Cambridge, CB2 0QQ, United Kingdom
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Canterbury, CT1 3NG, United Kingdom
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Wolverhampton, WV10 OQP, United Kingdom
Related Publications (4)
Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, Tedeschi A, Owen C, Skarbnik A, Lysak D, Eom KS, Simkovic M, Pavlovsky MA, Kater AP, Eichhorst B, Miller K, Munugalavadla V, Yu T, de Borja M, Ghia P; AMPLIFY investigators; AMPLIFY Investigators. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762. doi: 10.1056/NEJMoa2409804. Epub 2025 Feb 5.
PMID: 39976417DERIVEDAlfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
PMID: 39563886DERIVEDDavids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.
PMID: 34534514DERIVEDGordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol. 2021 Jan 30;12:2040620721989588. doi: 10.1177/2040620721989588. eCollection 2021.
PMID: 33796237DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer Brown
Dana Farber Mass General Brigham Cancer Care Inc
- PRINCIPAL INVESTIGATOR
Barbara Eichhorst
Universitätsklinikum Köln
- PRINCIPAL INVESTIGATOR
Arnon Kater
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- PRINCIPAL INVESTIGATOR
Paolo Ghia
OSPEDALE S. RAFFAELE - MILANO
- PRINCIPAL INVESTIGATOR
John Seymour
Peter MacCallum Cancer Ctr
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 6, 2019
First Posted
February 11, 2019
Study Start
February 25, 2019
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
December 27, 2024
Record last verified: 2024-12