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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Ibrutinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria 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 Key Exclusion Criteria 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zanubrutinib<br>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<br>* 160 mg orally twice daily<br>* Other names: Brukinsa;|
| Active Comparator: Ibrutinib<br>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<br>* Ibrutinib 420 mg orally once daily<br>* Other names: Imbruvica;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) as Determined by Investigator Assessment | ORR is percentage of participants with partial response (PR) or higher, (defined as Complete response/ Complete response with incomplete bone marrow recovery (CR/CRi) + PR + nodular PR) per investigator assessment using the modified 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for non-Hodgkin lymphoma (NHL)) for participants with Small lymphocytic lymphoma (SLL) | Up to approximately 3 years and 9 months | 
| ORR as Determined by Independent Review Committee (IRC) | ORR is the percentage of participants with PR or higher, (CR/CRi) + PR + nodular PR per IRC assessment using the modified 2008 IWCLL guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for NHL for participants with SLL | Up to approximately 3 years and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Determined by Independent Central Review |  | Up to 51 months | 
| Progression-free Survival Determined by Investigator Assessment |  | Up to 51 months | 
| Duration of Response Determined by Investigator Assessment |  | Up to 51 months | 
| Duration of Response Determined by Independent Central Review |  | Up to 51 months | 
| Time to Treatment Failure |  | Up to 51 months | 
| Overall Survival |  | Up to 51 months | 
| Patient Reported Outcomes as Assessed by EORTC-QLQ-C30 |  | Up to 51 months | 
| Patient Reported Outcomes as Assessed by EQ-5D-5L |  | Up to 51 months | 
| Incidence of Adverse Events as Assessed by CTCAE v4.03 [Safety and Tolerability] |  | 51 months | 
| Rate of Partial Response With Lymphocytosis (PR-L) or Higher Determined by Independent Central Review | Proportion of participants who achieve a CR/CRi + PR + nodular PR + PR-L | Up to 51 months | 
| Overall Response Rate Determined by Independent Central Review |  | 51 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, SLL, relapsed, refractory