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

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.

Sex

All

Minimum age

18 Years

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.

• BACKGROUNDBrown 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
• BACKGROUNDHillmen 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
• RESULTHillmen 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
• DERIVEDTam 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
• DERIVEDRhee 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.