A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (ALPINE)

A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is designed to compare the overall response rate of zanubrutinib versus ibrutinib in participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Ibrutinib

Detailed Description

This is a global, Phase 3, randomized study of zanubrutinib versus ibrutinib in 652 participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

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.

• Study Type: Interventional
• Enrollment (Actual): 652
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Foundation
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Frankston, Victoria, Australia, 3199
      • Peninsula Private Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Belgium
  • Wilrijk, Belgium, 2610
    • Gasthuiszusters Antwerpen Sint Augustinus
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Affliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Tongji Hospital of Tongji University
    • Shanghai, Shanghai, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China, 325000
      • The First Provincial Wenzhou Hospital of Zhejiang
• Czechia
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
  • Hradec Kralove, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 77900
    • Fakultni nemocnice Olomouc
  • Ostrava, Czechia, 708 00
    • Fakultni Nemocnice Ostrava
• France
  • Cesson Sevigne, France, 35510
    • Hôpital privé Sévigné
  • La Roche sur Yon, France, 85925
    • Centre Hospitalier Départemental de Vendée
  • Le Mans, France, 72037
    • Centre Hospitalier Le Mans
  • PierreBenite, France, 69495
    • Chu Hopital Lyon Sud
  • Poitiers, France, 86000
    • Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard
  • Tours, France, 37000
    • Chu Tours Hopital Bretonneau Service Pneumologie
• Germany
  • Hamm, Germany, 59063
    • Evangelisches Krankenhaus Hamm
  • Koln, Germany, 50937
    • Uniklinik Koln (Aor)
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Netherlands
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen
  • Nijmegen, Netherlands, 6525 GA
    • Albert Schweitzer Ziekenhuis
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Clinical Trials
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital (Canterbury Health Laboratories)
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Takapuna, New Zealand, 0622
    • North Shore Hospital
  • Tauranga, New Zealand, 3112
    • Tauranga Hospital
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital (Ccdhb)
• Poland
  • Bialystok, Poland, 15748
    • Interhem Opieka Szpitalna
  • Brzozow, Poland, 36-200
    • Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
  • Chorzow, Poland, 41-500
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Gdansk, Poland, 80-219
    • Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne Sc
  • Legnica, Poland, 59-220
    • Wojewodzki Szpital Specjalistyczny W Legnicy
  • Lodz, Poland, 93-510
    • Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
  • Poznan, Poland, 60-569
    • Examen Sp Z Oo
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias I Pujol
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall Dhebron
  • Girona, Spain, 17007
    • Ico Girona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Toledo, Spain, 45004
    • Hospital Virgen de la Salud
• Sweden
  • Lund, Sweden, 221 85
    • Skanes Universitetssjukhus I Lund
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna
• Turkey
  • Tekirdag, Turkey, 59100
    • Namik Kemal University
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Nhs Grampian Ppds
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
  • Canterbury, United Kingdom, CT1 3NG
    • Kent and Canterbury Hospital
  • Leeds, United Kingdom, LS9 7LP
    • St Jamess Institute of Oncology
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospitals Nhs Foundation Trust
  • Nottingham, United Kingdom, NG51PB
    • Nottingham University Hospitals NHS Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Sunderland, United Kingdom, SR4 7TP
    • Sunderland Royal Hospital
  • Waterlooville, United Kingdom, PO7 7XX
    • Genesiscare Oxford
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
  • Colorado
    • Boulder, Colorado, United States, 80303
      • Rocky Mountain Cancer Centers Boulder
  • Florida
    • Fort Myers, Florida, United States, 33901
      • SCRI Florida Cancer Specialists South
    • Saint Petersburg, Florida, United States, 33705
      • SCRI Florida Cancer Specialists North
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute Pavilion
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Forrest General Hospital Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Scri Hca Midwest Health
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance, Inc
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Springfield, Oregon, United States, 97477
      • Willamette Valley Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Scri Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104-2150
      • Texas Oncology Fort Worth Cancer Center
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio Medical Center Usor
    • Tyler, Texas, United States, 75702
      • Texas Oncology Tyler Longview
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care (Oncology and Hematology Associates of Southwest Virginia)
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria

1. Confirmed diagnosis of CLL or SLL that meets the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 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

Key Exclusion Criteria

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Zanubrutinib; 160 mg orally twice daily; Other Names: Brukinsa; BGB-3111
Active Comparator: 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.	Drug: Ibrutinib; Ibrutinib 420 mg orally once daily; Other Names: Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) Assessed by the Investigator	ORR is defined as the percentage of participants with a complete response (CR) / complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR) or partial response (PR) per investigator assessment. Disease response was assessed in accordance with the 2008 criteria of the International Workshop on CLL (IWCLL), with modification for treatment-related lymphocytosis in participants with CLL and in accordance with the Lugano classification in participants with SLL.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
ORR Assessed by the Independent Review Committee (IRC)	ORR is defined as the percentage of participants with a complete response (CR) / complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR) or partial response (PR) assessed by a blinded independent review committee. Overall response was assessed by the IRC for the purpose of regulatory filing with the Food and Drug Administration (FDA). Disease response was assessed in accordance with the 2008 criteria of the International Workshop on CLL (IWCLL), with modification for treatment-related lymphocytosis in participants with CLL and in accordance with the Lugano classification in participants with SLL.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Assessed by the Investigator	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Progression-free Survival Assessed by the Independent Review Committee	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Percentage of Participants With Atrial Fibrillation or Atrial Flutter	Participants were considered as having an atrial fibrillation/flutter event if they had a treatment-emergent AE of either "atrial fibrillation" or "atrial flutter".	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Duration of Response Assessed by the Independent Review Committee	DOR is defined as the time from the date that response criteria were first met to the date that disease progression was objectively documented or death, whichever occurred first, determined by independent central review. Median DOR was estimated using the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Duration of Response (DOR) Assessed by the Investigator	DOR is defined as the time from the date that response criteria were first met to the date that disease progression was objectively documented or death, whichever occurred first, determined by investigator assessment. Median DOR was estimated using the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Time to Treatment Failure	Time to treatment failure is defined as the time from randomization to discontinuation of study drug due to any reason. Median time to treatment failure was estimated by the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Independent Review Committee	The rate of partial response with lymphocytosis or better is defined as the percentage of participants who achieved a complete response or a complete response with incomplete bone marrow recovery (CR/CRi), nodular partial response, partial response, or partial response with lymphocytosis assessed by the blinded IRC. Disease response was assessed per iwCLL 2008 criteria, with modification for treatment-related lymphocytosis for participants with CLL and per Lugano classification for participants with SLL.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Investigator	The rate of partial response with lymphocytosis or better is defined as the percentage of participants who achieved a complete response or complete response with incomplete bone marrow recovery (CR/CRi), nodular partial response, partial response, or partial response with lymphocytosis as assessed by the investigator. Disease response was assessed according to the iwCLL 2008 criteria, with modification for treatment-related lymphocytosis for participants with CLL and in accordance with Lugano classification for participants with SLL. Partial response with lymphocytosis: blood lymphocytes decreased < 50% or increased from baseline, and otherwise meeting criteria for PR.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Overall Survival (OS)	Overall survival is defined as the time from randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.	From randomization to the final efficacy analysis cutoff date of 08 August 2022, median time on follow-up was 29.6 months (maximum of 45.2 months).
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning and Role Functioning Scores	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.	Baseline and Weeks 24 and 48
Change From Baseline in EORTC QLQ-C30 Symptom Scales of Fatigue, Nausea and Vomiting, Pain, and Diarrhoea	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Lower scores in symptom scales indicate better quality of life.	Baseline and Weeks 24 and 48
Change From Baseline in European Quality of Life 5-dimensions 5-levels Health Questionnaire (EQ-5D-5L) Visual Analog Scale (VAS)	The EQ-5D-5L VAS measures a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.	Baseline and Weeks 24 and 48
Number of Participants With Treatment-emergent Adverse Events (TEAE)	An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required hospitalization or prolongation of existing hospitalization; Resulted in disability/incapacity; Resulted in a congenital anomaly/birth defect; Was considered a significant medical AE by the investigator based on medical judgment	From first dose of study drug up to 30 days after last dose, up to the end of study data cutoff (28 February 2024); median (range) time on treatment was 41.2 (0.4-59.1) months in the zanubrutinib arm and 37.8 (0.1-60.4) months in the ibrutinib arm.

Other Outcome Measures

Outcome Measure	Time Frame
Correlation Between Prognostic and Predictive Biomarkers and Clinical Outcomes	Up to 51 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• 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, 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): August 8, 2022
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: November 2, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: CLL; relapsed; refractory; Chronic Lymphocytic Leukemia; SLL; Small Lymphocytic Lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Zanubrutinib; Ibrutinib
• Other Study ID Numbers: BGB-3111-305; 2018-001366-42 (EudraCT Number); CTR20190098 (Registry Identifier: ChinaDrugTrials.org)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No