A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
- Conditions
- Small Lymphocytic LymphomaChronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT03734016
- Lead Sponsor
- BeiGene
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 652
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zanubrutinib 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. Ibrutinib 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.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Assessed by the Investigator 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 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.ORR Assessed by the Independent Review Committee (IRC) 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 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.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Assessed by the Investigator 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). 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.
Progression-free Survival Assessed by the Independent Review Committee 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). 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.
Percentage of Participants With 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). Participants were considered as having an atrial fibrillation/flutter event if they had a treatment-emergent AE of either "atrial fibrillation" or "atrial flutter".
Duration of Response Assessed by the Independent Review Committee 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). 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.
Duration of Response (DOR) Assessed by the Investigator 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). 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.
Time to Treatment Failure 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 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.
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Independent Review Committee 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 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.Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Investigator 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 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.Overall Survival (OS) 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 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.
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 Baseline and Weeks 24 and 48 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.
Change From Baseline in EORTC QLQ-C30 Symptom Scales of Fatigue, Nausea and Vomiting, Pain, and Diarrhoea Baseline and Weeks 24 and 48 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.
Change From Baseline in European Quality of Life 5-dimensions 5-levels Health Questionnaire (EQ-5D-5L) Visual Analog Scale (VAS) Baseline and Weeks 24 and 48 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.
Number of Participants With Treatment-emergent Adverse Events (TEAE) 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. 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
Trial Locations
- Locations (115)
Barts Health Nhs Trust
🇬🇧London, United Kingdom
Genesiscare Oxford
🇬🇧Waterlooville, United Kingdom
Carti Cancer Center
🇺🇸Little Rock, Arkansas, United States
Scri Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Norton Cancer Institute Pavilion
🇺🇸Louisville, Kentucky, United States
Scri Hca Midwest Health
🇺🇸Kansas City, Missouri, United States
Nebraska Medical Center
🇺🇸Omaha, Nebraska, 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 North
🇺🇸Saint Petersburg, Florida, 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
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Forrest General Hospital Cancer Center
🇺🇸Hattiesburg, Mississippi, 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, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, 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, China
Tongji Hospital of Tongji University
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Institute of Hematology and Hospital of Blood Disease
🇨🇳Tianjin, Tianjin, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, 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 Kralove, Czechia
Fakultni Nemocnice Olomouc
🇨🇿Olomouc, Czechia
Fakultni Nemocnice Ostrava
🇨🇿Ostrava, Czechia
Hopital Prive Sevigne
🇫🇷Cesson Sevigne, 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
Evangelisches Krankenhaus Hamm
🇩🇪Hamm, Germany
Uniklinik Koln (Aor)
🇩🇪Koln, Germany
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, 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
🇵🇱Brzozow, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
🇵🇱Chorzow, 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
🇹🇷Tekirdag, Turkey
Nhs Grampian Ppds
🇬🇧Aberdeen, United Kingdom
Norfolk and Norwich University Hospitals Nhs Foundation Trust
🇬🇧Norwich, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, 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
Nottingham University Hospitals Nhs Trust
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom