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AzTrials

Chronic Lymphocytic LeukemiaPhase 3ALPINENCT03734016

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

A Phase 3 study testing Zanubrutinib and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by BeiGene at 115 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanubrutinib and Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
652 participants
Where
115 sitesin 15 countries
Study dates
1 Nov 2018to 28 Feb 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of CLL or SLL that meets the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
  • CLL/SLL requiring treatment per 2008 IWCLL criteria
  • Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
  • Measurable disease by computerized tomography (CT)/magnetic resonance imaging (MRI)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Life expectancy ≥ 6 months
  • Adequate bone marrow function
  • Adequate renal and hepatic function

Who cannot join

  • Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
  • Clinically significant cardiovascular disease.
  • 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
  • History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
  • History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
  • Severe or debilitating pulmonary disease
Show all 18Show fewer
  • Active fungal, bacterial, and/or viral infection requiring systemic therapy
  • Known central nervous system involvement by leukemia or lymphoma
  • Known infection with HIV or active viral hepatitis B or C infection
  • Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
  • Major surgery within 4 weeks of the first dose of study drug
  • Prior treatment with a (Burton's Kinase) BTK inhibitor
  • Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
  • Pregnant or lactating women
  • Vaccination with a live vaccine within 35 days prior to the first dose of study drug
  • Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
  • Concurrent participation in another therapeutic clinical trial
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

115 sites in 15 countries.

115 sites in 15 countries

United States30 sites

  • Augusta University

    Augusta, Georgia, 30912

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Rocky Mountain Cancer Centers Boulder

    Boulder, Colorado, 80303

  • Scri Tennessee Oncology Chattanooga

    Chattanooga, Tennessee, 37404

  • Duke University Hospital

    Durham, North Carolina, 27705

  • Scri Florida Cancer Specialists South

    Fort Myers, Florida, 33901

  • Texas Oncology Fort Worth Cancer Center

    Fort Worth, Texas, 76104-2150

  • Forrest General Hospital Cancer Center

    Hattiesburg, Mississippi, 39401

  • The University of Texas Md Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Scri Hca Midwest Health

    Kansas City, Missouri, 64132

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • Carti Cancer Center

    Little Rock, Arkansas, 72205

  • David Geffen School of Medicine At UCLA

    Los Angeles, California, 90095

  • Norton Cancer Institute Pavilion

    Louisville, Kentucky, 40207

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410

  • Atlantic Health System

    Morristown, New Jersey, 07960

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Columbia University Medical Center

    New York, New York, 10032

  • Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Blue Ridge Cancer Care (Oncology and Hematology Associates of Southwest Virginia)

    Roanoke, Virginia, 24014

  • Texas Oncology San Antonio Medical Center Usor

    San Antonio, Texas, 78240

  • Va Puget Sound Health Care System

    Seattle, Washington, 98108

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Medical Oncology Associates

    Spokane, Washington, 99208

  • Willamette Valley Cancer Center

    Springfield, Oregon, 97477

  • Scri Florida Cancer Specialists North

    St. Petersburg, Florida, 33705

  • Texas Oncology Tyler Longview

    Tyler, Texas, 75702

  • Clinical Research Alliance, Inc

    Westbury, New York, 11590

Other trials in United States

China19 sites

  • Peking University Third Hospital

    Beijing, Beijing Municipality, 100000

  • Beijing Friendship Hospital, Capital Medical University

    Beijing, Beijing Municipality, 100050

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

  • Guangdong Provincial Peoples Hospital

    Guangzhou, Guangdong, 510080

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510515

  • The First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310003

  • Jiangsu Province Hospital

    Nanjing, Jiangsu, 210029

  • Quanzhou First Affliated Hospital of Fujian Medical University

    Quanzhou, Fujian, 362000

  • Affiliated Zhongshan Hospital of Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Tongji Hospital of Tongji University

    Shanghai, Shanghai Municipality, 200092

  • Shengjing Hospital of China Medical University

    Shenyang, Liaoning, 110004

  • Institute of Hematology and Hospital of Blood Disease

    Tianjin, Tianjin Municipality, 300020

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin, Tianjin Municipality, 300060

  • The First Provincial Wenzhou Hospital of Zhejiang

    Wenzhou, Zhejiang, 325000

  • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

    Wuhan, Hubei, 430022

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450000

Other trials in China

United Kingdom12 sites

  • Nhs Grampian Ppds

    Aberdeen, AB25 2ZN

  • Birmingham Heartlands Hospital

    Birmingham, B9 5SS

  • The Royal Bournemouth and Christchurch Hospitals Nhs Foundation

    Bournemouth, BH7 7DW

  • Kent and Canterbury Hospital

    Canterbury, CT1 3NG

  • St Jamess Institute of Oncology

    Leeds, LS9 7LP

  • Barts Health Nhs Trust

    London, EC1A 7BE

  • Norfolk and Norwich University Hospitals Nhs Foundation Trust

    Norwich, NR4 7UY

  • Nottingham University Hospitals Nhs Trust

    Nottingham, NG51PB

  • Derriford Hospital

    Plymouth, PL6 8DH

  • Southampton General Hospital

    Southampton, SO16 6YD

  • Sunderland Royal Hospital

    Sunderland, SR4 7TP

  • Genesiscare Oxford

    Waterlooville, PO7 7XX

Other trials in United Kingdom

Spain10 sites

  • Hospital Universitari Germans Trias I Pujol

    Badalona, 08916

  • Hospital de La Santa Creu I Sant Pau

    Barcelona, 08025

  • Hospital Universitario Vall Dhebron

    Barcelona, 08035

  • Hospital Clinic I Provincial

    Barcelona, 08036

  • Ico Girona

    Girona, 17007

  • Hospital Universitario Ramon Y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Puerta de Hierro Majadahonda

    Majadahonda, 28222

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

  • Hospital Virgen de La Salud

    Toledo, 45004

Other trials in Spain

Poland9 sites

  • Interhem Opieka Szpitalna

    Bialystok, 15748

  • Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny

    Brzozów, 36-200

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

    Chorzów, 41-500

  • Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii

    Gdansk, 80-219

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-952

  • Malopolskie Centrum Medyczne Sc

    Krakow, 30-510

  • Wojewodzki Szpital Specjalistyczny W Legnicy

    Legnica, 59-220

  • Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi

    Lodz, 93-510

  • Examen Sp Z Oo

    Poznan, 60-569

Other trials in Poland

Australia7 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • Monash Health

    Clayton, Victoria, 3168

  • Peninsula Private Hospital

    Frankston, Victoria, 3199

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Icon Cancer Foundation

    South Brisbane, Queensland, 4101

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

Other trials in Australia

France6 sites

  • Hopital Prive Sevigne

    Cesson-Sévigné, 35510

  • Centre Hospitalier Departemental de Vendee

    La Roche-sur-Yon, 85925

  • Centre Hospitalier Le Mans

    Le Mans, 72037

  • Chu Hopital Lyon Sud

    PierreBenite, 69495

  • Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard

    Poitiers, 86000

  • Chu Tours Hopital Bretonneau Service Pneumologie

    Tours, 37000

Other trials in France

New Zealand6 sites

  • Middlemore Clinical Trials

    Auckland, 2025

  • Christchurch Hospital (Canterbury Health Laboratories)

    Christchurch, 8011

  • Waikato Hospital

    Hamilton, 3204

  • North Shore Hospital

    Takapuna, 0622

  • Tauranga Hospital

    Tauranga, 3112

  • Wellington Regional Hospital (Ccdhb)

    Wellington, 6021

Other trials in New Zealand

Czechia4 sites

  • Fakultni Nemocnice Brno

    Brno, 62500

  • Fakultni Nemocnice Hradec Kralove

    Hradec Králové, 50005

  • Fakultni Nemocnice Olomouc

    Olomouc, 77900

  • Fakultni Nemocnice Ostrava

    Ostrava, 708 00

Other trials in Czechia

Italy4 sites

  • Ospedale San Raffaele

    Milan, 20132

  • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

    Milan, 20162

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 00168

  • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino

    Torino, 10126

Other trials in Italy

Germany2 sites

  • Uniklinik Koln (Aor)

    Cologne, 50937

  • Evangelisches Krankenhaus Hamm

    Hamm, 59063

Other trials in Germany

Netherlands2 sites

  • Gelre Ziekenhuizen

    Apeldoorn, 7334 DZ

  • Albert Schweitzer Ziekenhuis

    Nijmegen, 6525 GA

Other trials in Netherlands

Sweden2 sites

  • Skanes Universitetssjukhus I Lund

    Lund, 221 85

  • Karolinska Universitetssjukhuset Solna

    Stockholm, 171 76

Other trials in Sweden

Belgium1 site

  • Gasthuiszusters Antwerpen Sint Augustinus

    Wilrijk, 2610

Other trials in Belgium

Turkey (Türkiye)1 site

  • Namik Kemal University

    Tekirdağ, 59100

Other trials in Turkey (Türkiye)

About this study

Official title: 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.

Read the 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.

Being tested
Zanubrutinib, Ibrutinib
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, CLL, SLL, relapsed, refractory
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZanubrutinibDrug

    Also called BGB-3111, Brukinsa

    160 mg orally twice daily

  • IbrutinibDrug

    Also called Imbruvica

    Ibrutinib 420 mg orally once daily

Study groups in NCT03734016
Study groupRoleWhat they receive
ZanubrutinibExperimentalParticipants 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.
Receives: Drug: Zanubrutinib
IbrutinibActive comparatorParticipants 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.
Receives: Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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).

  2. 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.

    Measured: 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 outcomes (13)

  1. 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.

    Measured: 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).

  2. 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.

    Measured: 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).

  3. 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".

    Measured: 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).

  4. 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.

    Measured: 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).

  5. 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.

    Measured: 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).

  6. 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.

    Measured: 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).

  7. 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.

    Measured: 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).

  8. 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.

    Measured: 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).

  9. 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.

    Measured: 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).

  10. 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.

    Measured: Baseline and Weeks 24 and 48

  11. 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.

    Measured: Baseline and Weeks 24 and 48

  12. 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.

    Measured: Baseline and Weeks 24 and 48

  13. 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

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2018
  2. Study start1 Nov 2018
  3. Primary completion8 Aug 2022
  4. Study completion28 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
652 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03734016
Sponsor's protocol ID
BGB-3111-305
Other IDs
2018-001366-42, CTR20190098, 2018
Acronym
ALPINE
Status last verified
Mar 2025
First submitted
2 Nov 2018
Last updated
30 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 36511784

  • 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.

    PubMed 36395435

  • 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.

    PubMed 32207333

  • Tam CS, Shadman M, Ong SY, Wu K, Salmi T, Korde R, Barnes G, Brown JR, Zhou K, Qiu L. Zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: health-related quality of life in a subgroup of Chinese patients in the ALPINE trial. Curr Med Res Opin. 2026 Jan;42(1):139-146. doi: 10.1080/03007995.2026.2623629. Epub 2026 Feb 13.

    PubMed 41686056

  • Rhee JW, Lamanna N, Aldairy W, Chen L, Zhang J, Ramirez D, White WB. Hypertension in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in ALPINE: a secondary analysis. Blood Neoplasia. 2025 Aug 4;2(4):100150. doi: 10.1016/j.bneo.2025.100150. eCollection 2025 Nov.

    PubMed 41424932

  • 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.

    PubMed 39853273

  • 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.

    PubMed 39316666

  • 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.

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  • 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.

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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. 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.

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Zanubrutinib and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by BeiGene at 115 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in United States, China, United Kingdom, Spain, Poland and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) Assessed by the Investigator (time frame: 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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03734016, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.

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