TriangleNCT03734016 · CITED IN SOURCE DOCUMENTS
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-03-30
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Response Rate (ORR) Assessed by the Investigator
ORR Assessed by the Independent Review Committee (IRC)
Progression-free Survival (PFS) Assessed by the Investigator
Progression-free Survival Assessed by the Independent Review Committee
Percentage of Participants With Atrial Fibrillation or Atrial Flutter
Duration of Response Assessed by the Independent Review Committee
Duration of Response (DOR) Assessed by the Investigator
Time to Treatment Failure
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Independent Review Committee
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Investigator
Overall Survival (OS)
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
Change From Baseline in EORTC QLQ-C30 Symptom Scales of Fatigue, Nausea and Vomiting, Pain, and Diarrhoea
Change From Baseline in European Quality of Life 5-dimensions 5-levels Health Questionnaire (EQ-5D-5L) Visual Analog Scale (VAS)
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Drug: Zanubrutinib
- label
- Zanubrutinib
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: Ibrutinib
- label
- Ibrutinib
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Zanubrutinib
- description
- 160 mg orally twice daily
- name
- Zanubrutinib
- other Names
- BGB-3111
- Brukinsa
- type
- DRUG
- arm Group Labels
- Ibrutinib
- description
- Ibrutinib 420 mg orally once daily
- name
- Ibrutinib
- other Names
- Imbruvica
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 652
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- 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).
- description
- 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.
- measure
- ORR Assessed by the Independent Review Committee (IRC)
- 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).
- secondary Outcomes
- description
- 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.
- measure
- Progression-free Survival (PFS) 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).
- description
- 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.
- measure
- Progression-free Survival Assessed by the Independent Review Committee
- 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).
- description
- Participants were considered as having an atrial fibrillation/flutter event if they had a treatment-emergent AE of either "atrial fibrillation" or "atrial flutter".
- measure
- Percentage of Participants With Atrial Fibrillation or Atrial Flutter
- 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).
- description
- 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.
- measure
- Duration of Response Assessed by the Independent Review Committee
- 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).
- description
- 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.
- measure
- Duration of Response (DOR) 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).
- description
- 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.
- measure
- Time to Treatment Failure
- 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).
- description
- 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.
- measure
- Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Independent Review Committee
- 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).
- description
- 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.
- measure
- Rate of Partial Response With Lymphocytosis (PR-L) or Higher 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).
- description
- 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.
- measure
- Overall Survival (OS)
- 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).
- description
- 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.
- measure
- 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
- time Frame
- Baseline and Weeks 24 and 48
- description
- 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.
- measure
- Change From Baseline in EORTC QLQ-C30 Symptom Scales of Fatigue, Nausea and Vomiting, Pain, and Diarrhoea
- time Frame
- Baseline and Weeks 24 and 48
- description
- 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.
- measure
- Change From Baseline in European Quality of Life 5-dimensions 5-levels Health Questionnaire (EQ-5D-5L) Visual Analog Scale (VAS)
- time Frame
- Baseline and Weeks 24 and 48
Full study description
- 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.
Source references
- references
- citation
- 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.
- pmid
- 36511784
- type
- BACKGROUND
- citation
- 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.
- pmid
- 36395435
- type
- BACKGROUND
- citation
- 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.
- pmid
- 32207333
- type
- RESULT
- citation
- 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.
- pmid
- 41686056
- type
- DERIVED
- citation
- 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.
- pmid
- 41424932
- type
- DERIVED
- citation
- 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.
- pmid
- 39853273
- type
- DERIVED
- citation
- 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.
- pmid
- 39316666
- type
- DERIVED
- citation
- 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.
- pmid
- 38888616
- type
- DERIVED
- citation
- 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.
- pmid
- 38502198
- type
- DERIVED
- citation
- 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.
- pmid
- 38088119
- type
- DERIVED
- citation
- 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.
- pmid
- 37752892
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-4501714e33308aae3f67
- requested nct id
- NCT03734016
- primary nct id
- NCT03734016
- source kind
- fda_spl_label
- source record id
- 29341b77-7deb-445a-ae2c-a8e01c932daf
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- payload sha256
- 4babe47130119a881d3f9580b9438ccec3842de684d8602a48c69963061fbfcf
- payload
- application numbers
- NDA213217
- NDA218785
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-4501714e33308aae3f67
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03734016
- occurrences
- context exact
- efficacy of BRUKINSA in patients with relapsed or refractory CLL/SLL was evaluated in ALPINE, a randomized, multicenter, open-label, actively controlled trial (NCT03734016). The trial enrolled 652 patients with relapsed or refractory CLL/SLL after at least 1 systemic therapy. The patients were randomized in a 1:1 ratio to receive
- end
- 13097
- exact text
- NCT03734016
- start
- 13086
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00100.json
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- source json pointer
- /results/49/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 29341b77-7deb-445a-ae2c-a8e01c932daf
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 568216a9881d887242989d7a2614d2fe2f7e4dd08e6f60e050342cb67cd8e676
- spl effective time
- 20260721
- spl set id
- 3e08fe23-d70e-424c-bc51-1222e320f902
Preserved source evidence · Not medical advice