A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
NCT ID: NCT03734016
Last Updated: 2025-03-30
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
652 participants
INTERVENTIONAL
2018-11-01
2024-02-28
Brief Summary
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Detailed Description
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The primary efficacy endpoint is overall response rate determined by investigator assessment. Participants were randomized in a 1:1 manner to either zanubrutinib or ibrutinib. Treatment with zanubrutinib and ibrutinib was open label.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Zanubrutinib
Participants received 160 mg zanubrutinib orally twice daily until disease progression, intolerable toxicity, initiation of alternative anticancer therapy, investigator/Sponsor decision, need for prohibited medication, study withdrawal, or pregnancy.
Zanubrutinib
160 mg orally twice daily
Ibrutinib
Participants received Ibrutinib 420 mg orally once daily until disease progression, intolerable toxicity, initiation of alternative anticancer therapy, investigator/Sponsor decision, need for prohibited medication, study withdrawal, or pregnancy.
Ibrutinib
Ibrutinib 420 mg orally once daily
Interventions
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Zanubrutinib
160 mg orally twice daily
Ibrutinib
Ibrutinib 420 mg orally once daily
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. CLL/SLL requiring treatment per 2008 IWCLL criteria
3. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
4. Measurable disease by computerized tomography (CT)/magnetic resonance imaging (MRI)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
6. Life expectancy ≥ 6 months
7. Adequate bone marrow function
8. Adequate renal and hepatic function
Exclusion Criteria
2. Clinically significant cardiovascular disease.
3. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast
4. History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
5. History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
6. Severe or debilitating pulmonary disease
7. Active fungal, bacterial, and/or viral infection requiring systemic therapy
8. Known central nervous system involvement by leukemia or lymphoma
9. Known infection with HIV or active viral hepatitis B or C infection
10. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
11. Major surgery within 4 weeks of the first dose of study drug
12. Prior treatment with a (Burton's Kinase) BTK inhibitor
13. Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
14. Pregnant or lactating women
15. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
16. Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
17. Concurrent participation in another therapeutic clinical trial
18 Years
ALL
No
Sponsors
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BeiGene
INDUSTRY
Responsible Party
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Principal Investigators
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Study Director
Role: STUDY_DIRECTOR
BeiGene
Locations
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Carti Cancer Center
Little Rock, Arkansas, United States
David Geffen School of Medicine At UCLA
Los Angeles, California, United States
Rocky Mountain Cancer Centers Boulder
Boulder, Colorado, United States
Scri Florida Cancer Specialists South
Fort Myers, Florida, United States
Scri Florida Cancer Specialists North
St. Petersburg, Florida, United States
Augusta University
Augusta, Georgia, United States
Norton Cancer Institute Pavilion
Louisville, Kentucky, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Forrest General Hospital Cancer Center
Hattiesburg, Mississippi, United States
Scri Hca Midwest Health
Kansas City, Missouri, United States
Nebraska Medical Center
Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
Atlantic Health System
Morristown, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Columbia University Medical Center
New York, New York, United States
Clinical Research Alliance, Inc
Westbury, New York, United States
Duke University Hospital
Durham, North Carolina, United States
Oregon Health and Science University
Portland, Oregon, United States
Willamette Valley Cancer Center
Springfield, Oregon, United States
Scri Tennessee Oncology Chattanooga
Chattanooga, Tennessee, United States
Sarah Cannon Cancer Center
Nashville, Tennessee, United States
Texas Oncology Fort Worth Cancer Center
Fort Worth, Texas, United States
The University of Texas Md Anderson Cancer Center
Houston, Texas, United States
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, United States
Texas Oncology San Antonio Medical Center Usor
San Antonio, Texas, United States
Texas Oncology Tyler Longview
Tyler, Texas, United States
Blue Ridge Cancer Care (Oncology and Hematology Associates of Southwest Virginia)
Roanoke, Virginia, United States
Va Puget Sound Health Care System
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Medical Oncology Associates
Spokane, Washington, United States
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Princess Alexandra Hospital
Brisbane, Queensland, Australia
Icon Cancer Foundation
South Brisbane, Queensland, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Monash Health
Clayton, Victoria, Australia
Peninsula Private Hospital
Frankston, Victoria, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
Gasthuiszusters Antwerpen Sint Augustinus
Wilrijk, , Belgium
Peking University Third Hospital
Beijing, Beijing Municipality, China
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Quanzhou First Affliated Hospital of Fujian Medical University
Quanzhou, Fujian, China
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Jiangsu Province Hospital
Nanjing, Jiangsu, China
The First Hospital of Jilin University
Changchun, Jilin, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, China
Affiliated Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, China
Tongji Hospital of Tongji University
Shanghai, Shanghai Municipality, China
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Institute of Hematology and Hospital of Blood Disease
Tianjin, Tianjin Municipality, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
The First Provincial Wenzhou Hospital of Zhejiang
Wenzhou, Zhejiang, China
Fakultni Nemocnice Brno
Brno, , Czechia
Fakultni Nemocnice Hradec Kralove
Hradec Králové, , Czechia
Fakultni Nemocnice Olomouc
Olomouc, , Czechia
Fakultni Nemocnice Ostrava
Ostrava, , Czechia
Hopital Prive Sevigne
Cesson-Sévigné, , France
Centre Hospitalier Departemental de Vendee
La Roche-sur-Yon, , France
Centre Hospitalier Le Mans
Le Mans, , France
Chu Hopital Lyon Sud
PierreBenite, , France
Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard
Poitiers, , France
Chu Tours Hopital Bretonneau Service Pneumologie
Tours, , France
Uniklinik Koln (Aor)
Cologne, , Germany
Evangelisches Krankenhaus Hamm
Hamm, , Germany
Ospedale San Raffaele
Milan, , Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, , Italy
Fondazione Policlinico Universitario Agostino Gemelli
Roma, , Italy
Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
Torino, , Italy
Gelre Ziekenhuizen
Apeldoorn, , Netherlands
Albert Schweitzer Ziekenhuis
Nijmegen, , Netherlands
Middlemore Clinical Trials
Auckland, , New Zealand
Christchurch Hospital (Canterbury Health Laboratories)
Christchurch, , New Zealand
Waikato Hospital
Hamilton, , New Zealand
North Shore Hospital
Takapuna, , New Zealand
Tauranga Hospital
Tauranga, , New Zealand
Wellington Regional Hospital (Ccdhb)
Wellington, , New Zealand
Interhem Opieka Szpitalna
Bialystok, , Poland
Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
Brzozów, , Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów, , Poland
Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
Gdansk, , Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, , Poland
Malopolskie Centrum Medyczne Sc
Krakow, , Poland
Wojewodzki Szpital Specjalistyczny W Legnicy
Legnica, , Poland
Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
Lodz, , Poland
Examen Sp Z Oo
Poznan, , Poland
Hospital Universitari Germans Trias I Pujol
Badalona, , Spain
Hospital de La Santa Creu I Sant Pau
Barcelona, , Spain
Hospital Universitario Vall Dhebron
Barcelona, , Spain
Hospital Clinic I Provincial
Barcelona, , Spain
Ico Girona
Girona, , Spain
Hospital Universitario Ramon Y Cajal
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, , Spain
Hospital Universitario Marques de Valdecilla
Santander, , Spain
Hospital Virgen de La Salud
Toledo, , Spain
Skanes Universitetssjukhus I Lund
Lund, , Sweden
Karolinska Universitetssjukhuset Solna
Stockholm, , Sweden
Namik Kemal University
Tekirdağ, , Turkey (Türkiye)
Nhs Grampian Ppds
Aberdeen, , United Kingdom
Birmingham Heartlands Hospital
Birmingham, , United Kingdom
The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
Bournemouth, , United Kingdom
Kent and Canterbury Hospital
Canterbury, , United Kingdom
St Jamess Institute of Oncology
Leeds, , United Kingdom
Barts Health Nhs Trust
London, , United Kingdom
Norfolk and Norwich University Hospitals Nhs Foundation Trust
Norwich, , United Kingdom
Nottingham University Hospitals Nhs Trust
Nottingham, , United Kingdom
Derriford Hospital
Plymouth, , United Kingdom
Southampton General Hospital
Southampton, , United Kingdom
Sunderland Royal Hospital
Sunderland, , United Kingdom
Genesiscare Oxford
Waterlooville, , United Kingdom
Countries
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References
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Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13.
Hillmen P, Eichhorst B, Brown JR, Lamanna N, O'Brien SM, Tam CS, Qiu L, Kazmierczak M, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Shadman M, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Ji M, Yecies J, Idoine A, Wu K, Huang J, Jurczak W. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial. J Clin Oncol. 2023 Feb 10;41(5):1035-1045. doi: 10.1200/JCO.22.00510. Epub 2022 Nov 17.
Hillmen P, Brown JR, Eichhorst BF, Lamanna N, O'Brien SM, Qiu L, Salmi T, Hilger J, Wu K, Cohen A, Huang J, Tam CS. ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Future Oncol. 2020 Apr;16(10):517-523. doi: 10.2217/fon-2019-0844. Epub 2020 Mar 24.
Brown JR, Li J, Eichhorst BF, Lamanna N, O'Brien SM, Tam CS, Qiu L, Huang R, Shi Y, Idoine A, Salmi T, Cohen AC, Shadman M. Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study. Blood Adv. 2025 Apr 22;9(8):1918-1926. doi: 10.1182/bloodadvances.2024014206.
Brown JR, Eichhorst B, Lamanna N, O'Brien SM, Tam CS, Qiu L, Jurczak W, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Wang M, Salmi T, Wang L, Li J, Wu K, Cohen A, Shadman M. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024 Dec 26;144(26):2706-2717. doi: 10.1182/blood.2024024667.
Zhou K, Wang T, Pan L, Xu W, Jin J, Zhang W, Hu Y, Hu J, Feng R, Li P, Liu Z, Liu P, Jing H, Gao S, Zhang H, Yu K, Wang Z, Zhu X, Sun Z, Li F, Yan D, Weng J, Fu L, Wang L, Salmi T, Wu K, Qiu L. Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE. Ann Hematol. 2024 Oct;103(10):4183-4191. doi: 10.1007/s00277-024-05823-8. Epub 2024 Jun 18.
Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M. Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment. Future Oncol. 2024 Apr;20(12):717-726. doi: 10.2217/fon-2023-0849. Epub 2023 Dec 13.
Tam CS, Lamanna N, O'Brien SM, Qiu L, Yang K, Barnes G, Wu K, Salmi T, Brown JR. Health-related quality of life outcomes associated with zanubrutinib versus ibrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from the ALPINE Trial. Curr Med Res Opin. 2023 Nov;39(11):1497-1503. doi: 10.1080/03007995.2023.2262378. Epub 2023 Oct 27.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2018-001366-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CTR20190098
Identifier Type: REGISTRY
Identifier Source: secondary_id
BGB-3111-305
Identifier Type: -
Identifier Source: org_study_id
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