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

NCT ID: NCT03836261

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

984 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-25

Study Completion Date

2027-01-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Chronic Lymphocytic Leukemia

Keywords

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CLL Chronic Leukemia Lymphocytic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Acalabrutinib, Venetoclax

Acalabrutinib in combination with Venetoclax

Group Type EXPERIMENTAL

Acalabrutinib

Intervention Type DRUG

Acalabrutinib,

Venetoclax

Intervention Type DRUG

Venetoclax

Acalabrutinib, Venetoclax, Obinutuzumab

Acalabrutinib in combination with Venetoclax with Obinutuzumab

Group Type EXPERIMENTAL

Acalabrutinib

Intervention Type DRUG

Acalabrutinib,

Venetoclax

Intervention Type DRUG

Venetoclax

Obinutuzumab

Intervention Type DRUG

Obinutuzumab

Chemoimmunotherapy

Chemoimmunotherapy

FCR: Fludarabine, Cyclophosphamide and Rituximab

BR: Bendamustine and Rituximab

Group Type ACTIVE_COMPARATOR

Chemoimmunotherapy

Intervention Type DRUG

fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)

Interventions

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Acalabrutinib

Acalabrutinib,

Intervention Type DRUG

Venetoclax

Venetoclax

Intervention Type DRUG

Chemoimmunotherapy

fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)

Intervention Type DRUG

Obinutuzumab

Obinutuzumab

Intervention Type DRUG

Other Intervention Names

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Calquence (acalabrutinib) Venclyxto, Venclexta Gazyva, Gazyvaro

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Acerta Pharma BV

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jennifer Brown

Role: PRINCIPAL_INVESTIGATOR

Dana Farber Mass General Brigham Cancer Care Inc

Barbara Eichhorst

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Köln

Arnon Kater

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Paolo Ghia

Role: PRINCIPAL_INVESTIGATOR

OSPEDALE S. RAFFAELE - MILANO

John Seymour

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Ctr

Locations

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Los Angeles, California, United States

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Redondo Beach, California, United States

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Fort Wayne, Indiana, United States

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Wichita, Kansas, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Canton, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Fort Sam Houston, Texas, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Capital Federal, , Argentina

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Córdoba, , Argentina

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Adelaide, , Australia

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Darlinghurst, , Australia

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Heidelberg, , Australia

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Kogarah, , Australia

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Melbourne, , Australia

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Nedlands, , Australia

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Waratah, , Australia

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Woolloongabba, , Australia

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Krems, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Goiânia, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Vratsa, , Bulgaria

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Chongqing, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Nanchang, , China

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Nanjing, , China

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Shenyang, , China

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Shenyang, , China

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Tianjin, , China

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Ürümqi, , China

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Wenzhou, , China

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Wuhan, , China

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Wuhan, , China

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Xi'an, , China

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Zhengzhou, , China

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Zhengzhou, , China

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Brno, , Czechia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Ostrava - Poruba, , Czechia

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Plzen - Lochotin, , Czechia

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Prague, , Czechia

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Aarhus, , Denmark

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Copenhagen, , Denmark

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Roskilde, , Denmark

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Montpellier, , France

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Paris, , France

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Rennes, , France

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Rouen, , France

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Toulouse, , France

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Villejuif, , France

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Paderborn, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Kaposvár, , Hungary

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Tel Litwinsky, , Israel

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Novara, , Italy

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Ravenna, , Italy

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Torino, , Italy

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's-Hertogenbosch, , Netherlands

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Almere Stad, , Netherlands

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Amsterdam, , Netherlands

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Arnhem, , Netherlands

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Breda, , Netherlands

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Brzozów, , Poland

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Bydgoszcz, , Poland

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Gdynia, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Sochi, , Russia

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Tula, , Russia

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Volgograd, , Russia

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Dammam, , Saudi Arabia

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Jeddah, , Saudi Arabia

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Riyadh, , Saudi Arabia

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Bratislava, , Slovakia

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Bloemfontein, , South Africa

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Cape Town, , South Africa

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Pretoria, , South Africa

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Randburg, , South Africa

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Soweto, , South Africa

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Badalona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Salamanca, , Spain

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Santander, , Spain

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Valencia, , Spain

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Gothenburg, , Sweden

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Örebro, , Sweden

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Uppsala, , Sweden

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan, , Taiwan

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kurupelit, , Turkey (Türkiye)

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Talas, , Turkey (Türkiye)

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Cambridge, , United Kingdom

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Canterbury, , United Kingdom

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Wolverhampton, , United Kingdom

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Countries

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Belgium Mexico Peru Ukraine United States Argentina Australia Austria Brazil Bulgaria Canada China Czechia Denmark France Germany Hungary Israel Italy Netherlands Poland Russia Saudi Arabia Slovakia South Africa South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39976417 (View on PubMed)

Alfaifi 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.

Reference Type DERIVED
PMID: 39563886 (View on PubMed)

Davids 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.

Reference Type DERIVED
PMID: 34534514 (View on PubMed)

Gordon 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.

Reference Type DERIVED
PMID: 33796237 (View on PubMed)

Other Identifiers

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ACE-CL-311

Identifier Type: -

Identifier Source: org_study_id

D8221C00001

Identifier Type: OTHER

Identifier Source: secondary_id

2023-509349-11-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-002443-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NCT05211856

Identifier Type: -

Identifier Source: nct_alias