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

BeiGene

Status and phase: Completed; Phase 3

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Ibrutinib; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03734016

2018-001366-42 (EudraCT Number)

CTR20190098 (Registry Identifier)

BGB-3111-305

Details and patient eligibility

About

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.

Full 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.

Enrollment: 652 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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652 participants in 2 patient groups

Zanubrutinib

Experimental group

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.

Treatment:

Drug: Zanubrutinib

Ibrutinib

Active Comparator group

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.

Treatment:

Drug: Ibrutinib