Description:
This study will enroll subjects with previously untreated CLL/SLL into three cohorts (Cohort
1 without del[17p] and Cohorts 2 and 3 with del[17p]). Cohort 1 subjects will receive either
zanubrutinib alone or "bendamustine (B) and rituximab (R)". Cohort 2 subjects will receive
zanubrutinib alone. Once Cohort 2 has finished enrollment, Cohort 3 will be opened in
selected countries/sites where patients will receive zanubrutinib and venetoclax. The primary
purpose is to evaluate the efficacy and safety of zanubrutinib versus bendamustine and
rituximab in Cohort 1.
Title
- Brief Title: A Study Comparing BGB-3111 With Bendamustine Plus Rituximab in Patients With Previously Untreated CLL or SLL
- Official Title: An International, Phase 3, Open-Label, Randomized Study of BGB-3111 Compared With Bendamustine Plus Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL)
Clinical Trial IDs
- ORG STUDY ID:
BGB-3111-304 (Sequoia)
- NCT ID:
NCT03336333
Conditions
- Chronic Lymphocytic Leukemia
- Small Lymphocytic Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| BGB-3111 | | BGB-3111 (patients without del[17p]) |
| Bendamustine | Treanda, Ribomustin, and Levact | B+R |
| Rituximab | Rituxan, MabThera | B+R |
Purpose
This study will enroll subjects with previously untreated CLL/SLL into two cohorts (Cohort 1
without del[17p] and Cohort 2 with del[17p]). Cohort 1 subjects will receive either "BGB-3111
alone" or "bendamustine (B) and rituximab (R)". Cohort 2 subjects will receive BGB-3111
alone. The primary purpose is to evaluate the efficacy and safety of BGB-3111 versus
bendamustine and rituximab in Cohort 1.
Detailed Description
This is a global phase 3, open label, randomized study of BGB-3111 versus bendamustine plus
rituximab (B+R) in subjects with previously untreated chronic lymphocytic leukemia or small
lymphocytic lymphoma (CLL/SLL), including subjects without del(17p) [Cohort 1] and subjects
with del(17p) [Cohort 2]. Subjects in Cohort 1 are randomized 1:1 to BGB-3111 (Arm A) or
bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage,
immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region.
Subjects in Cohort 2 receive treatment with BGB-3111.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| BGB-3111 (patients without del[17p]) | Experimental | Approximately 210 subjects in Cohort 1 to receive BGB-3111 | |
| B+R | Experimental | Approximately 210 subjects in Cohort 1 to receive bendamustine plus rituximab | |
| BGB-3111 patients with del[17p]) | Experimental | Approximately 47 subjects in Cohort 2 to receive BGB-3111 | |
Eligibility Criteria
Inclusion Criteria: All subjects
1. Unsuitable for chemoimmunotherapy with FCR in the opinion of the investigator.
2. Confirmed diagnosis of CD20-positive CLL or SLL.
3. Binet Stage C disease, or Binet Stage B or A disease requiring treatment.
4. ECOG performance status of 0, 1 or 2.
5. Life expectancy ≥ 6 months.
6. Adequate bone marrow function.
7. Adequate renal and hepatic function.
8. Females of childbearing potential and non-sterile males must agree to use highly
effective methods of birth control throughout the course of study
9. Male patients are eligible if vasectomized or if they agree to use of barrier
contraception with other methods described above throughout the course of study.
10. Written informed consent.
Exclusion Criteria: All subjects
1. Previous systemic treatment for CLL/SLL.
2. Known prolymphocytic leukemia or history of or suspected Richter's transformation.
3. Clinically significant cardiovascular disease.
4. Prior malignancy within the past 3 years, except for curatively treated basal or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
cervix of breast.
5. Major surgery or significant injury ≤ 4 weeks prior to start of study treatment.
6. History of severe bleeding disorder.
7. History of stroke or intracranial hemorrhage within 6 months before the first dose of
study drug.
8. Severe or debilitating pulmonary disease.
9. Inability to swallow capsules or disease affecting gastrointestinal function.
10. Known central nervous system involvement by leukemia or lymphoma.
11. Active infection requiring systemic treatment.
12. Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
infection.
13. Vaccination with live vaccine within 35 days prior to the first dose of study drug.
14. Known hypersensitivity to BGB-3111, bendamustine, or rituximab or any other
ingredients of the study drugs.
15. Requires ongoing treatment with strong CYP3A inhibitor or inducer.
16. Pregnant or nursing females.
17. Concurrent participation in another therapeutic clinical trial.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Progression-free survival between treatment groups in Cohort 1 (BGB-3111 vs. bendamustine plus rituximab) as determined by independent central review |
| Time Frame: | From randomization to the date of first documentation of disease progression or death, whichever occurs first, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Overall response rate between treatment groups in Cohort 1 as determined by independent central review and by investigator assessment. |
| Time Frame: | From time of best response recorded from randomization until data cut or start of new anticancer treatment, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival between treatment groups in Cohort 1 |
| Time Frame: | From time of randomization until date of death due to any reason, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response between treatment groups in Cohort 1 determined by independent central review and by investigator assessment |
| Time Frame: | From date that response criteria are first met to the date of first documentation of disease progression or death, whichever occurs first, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival between treatment groups in Cohort 1 determined by investigator assessment |
| Time Frame: | From randomization to the date of first documentation of disease progression or death, whichever occurs first, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Overall response rate in Cohort 2 as determined in independent central review |
| Time Frame: | From time of best response recorded from randomization until data cut or start of new anticancer treatment, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Overall survival in Cohort 2 |
| Time Frame: | From time of first BGB-3111 dose administration until date of death due to any reason, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival in Cohort 2 determined by independent central review |
| Time Frame: | From the date of first BGB-3111 dose administration to the date of first documentation of disease progression or death, whichever occurs first, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response in Cohort 2 determined by independent central review |
| Time Frame: | From date that response criteria are first met to the date of first documentation of disease progression or death whichever occurs first, assessed up to 5 years. |
| Safety Issue: | |
| Description: | |
| Measure: | Incidence, nature and severity of adverse events between treatment groups in Cohort 1 |
| Time Frame: | From date of first study drug dose to approximately 30 days after end of treatment |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | BeiGene |
Trial Keywords
- BGB-3111
- BTK inhibitor
- bendamustine
- rituximab
- Phase 3
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