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A Study Comparing BGB-3111 With Bendamustine Plus Rituximab in Patients With Previously Untreated CLL or SLL (SEQUOIA)

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ClinicalTrials.gov Identifier: NCT03336333
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : November 4, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: Zanubrutinib Drug: Bendamustine Drug: Rituximab Drug: Venetoclax Phase 3

Detailed Description:
This is a global phase 3, open label, randomized study of zanubrutinib 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 and Cohort 3]. Subjects in Cohort 1 are randomized 1:1 to zanubrutinib (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 will receive treatment with zanubrutinib. Subjects in Cohort 3 will receive treatment with zanubrutinib and venetoclax.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 2, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: Zanubrutinib (patients without del[17p])
Approximately 225 subjects in Cohort 1 to receive zanubrutinib
Drug: Zanubrutinib
Zanubrutinib will be administered as two 80-mg capsules by mouth twice a day (160 mg twice a day)
Other Name: BGB-3111

Experimental: B+R
Approximately 225 subjects in Cohort 1 to receive bendamustine plus rituximab
Drug: Bendamustine
Bendamustine will be administered intravenously at a dose of 90 mg/m2/day on the first 2 days of each cycle for 6 cycles. 1 cycle = 28 days.
Other Name: Treanda, Ribomustin, and Levact

Drug: Rituximab
Rituximab will be administered intravenously at a dose of 375 mg/m2 on day 0 of cycle 1, and at a dose of 500 mg/m2 on day 1 of cycles 2 to 6. 1 cycle = 28 days.
Other Name: Rituxan, MabThera

Experimental: Zanubrutinib patients with del[17p])
Approximately 100 subjects in Cohort 2 to receive zanubrutinib
Drug: Zanubrutinib
Zanubrutinib will be administered as two 80-mg capsules by mouth twice a day (160 mg twice a day)
Other Name: BGB-3111

Experimental: Zanubrutinib and venetoclax (patients with del[17p])
Approximately 50 subjects in Cohort 3 to receive BGB-3111 and venetoclax
Drug: Zanubrutinib
Zanubrutinib will be administered as two 80-mg capsules by mouth twice a day (160 mg twice a day)
Other Name: BGB-3111

Drug: Venetoclax
Venetoclax will be administered by mouth once daily.
Other Name: Venclexta, Venclyxto




Primary Outcome Measures :
  1. Progression-free survival between treatment groups in Cohort 1 (Zanubrutinib vs. B+R) as determined by independent central review (ICR). [ Time Frame: Up to 5 years. ]

Secondary Outcome Measures :
  1. Overall response rate between treatment groups in Cohort 1 [ Time Frame: Up to 5 years. ]
  2. Overall survival between treatment groups in Cohort 1. [ Time Frame: Up to 5 years. ]
  3. Duration of response between treatment groups in Cohort 1. [ Time Frame: Up to 5 years. ]
  4. Progression-free survival between treatment groups in Cohort 1 determined by investigator assessment (IA). [ Time Frame: Up to 5 years. ]
  5. Patient-reported outcomes in Cohort 1 measured by the EQ-5D-5L questionnaire. [ Time Frame: Up to 5 years. ]
  6. Overall response rate in Cohort 2. [ Time Frame: Up to 5 years. ]
  7. Progression-free survival in Cohort 2 as determined by ICR. [ Time Frame: Up to 5 years. ]
  8. Duration of response in Cohort 2 as determined by ICR. [ Time Frame: Up to 5 years. ]
  9. Overall response rate in Cohort 3. [ Time Frame: Up to 5 years. ]
  10. Progression-free survival in Cohort 3 as determined by ICR. [ Time Frame: Up to 5 years. ]
  11. Duration of response in Cohort 3 as determined by ICR. [ Time Frame: Up to 5 years. ]
  12. Rate of undetectable minimal residual disease in Cohort 3. [ Time Frame: Up to 5 years. ]
  13. Descriptive statistics will be used to summarize rate of adverse events. [ Time Frame: Up to 5 years. ]
  14. Plasma zanubrutinib concentrations will be summarized by scheduled time of collection. [ Time Frame: Up to 5 years. ]
  15. Patient-reported outcomes in Cohort 1 measured by the EORTC QLQ-C30 questionnaire. [ Time Frame: Up to 5 years. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: All subjects

  • Unsuitable for chemoimmunotherapy with FCR
  • Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment.
  • Measurable disease by imaging
  • ECOG performance status of 0, 1 or 2.
  • Life expectancy ≥ 6 months.
  • Adequate bone marrow function.
  • Adequate renal and hepatic function.

Exclusion Criteria: All subjects

  • Previous systemic treatment for CLL/SLL.
  • Requires ongoing need for corticosteroid treatment.
  • Known prolymphocytic leukemia or history of or 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 of breast, or localized Gleason score 6 prostate cancer.
  • History of severe bleeding disorder.
  • History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
  • Severe or debilitating pulmonary disease.
  • Inability to swallow capsules or disease affecting gastrointestinal function.
  • Active infection requiring systemic treatment.
  • Known central nervous system involvement by leukemia or lymphoma
  • Underlying medical condition that will render the administration of study drug hazardous or obscure interpretation of toxicity or AEs
  • Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C infection.
  • Major surgery ≤ 4 weeks prior to start of study treatment.
  • Pregnant or nursing females.
  • Vaccination with live vaccine within 35 days prior to the first dose of study drug.
  • Ongoing alcohol or drug addiction
  • Known hypersensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax (as applicable) or any other ingredients of the study drugs.
  • Requires ongoing treatment with strong CYP3A inhibitor or inducer.
  • Concurrent participation in another therapeutic clinical trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03336333


Contacts
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Contact: BeiGene +1-877-828-5568 clinicaltrials@beigene.com

  Show 160 Study Locations
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Jason Paik, MD BeiGene

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03336333     History of Changes
Other Study ID Numbers: BGB-3111-304
2017-001551-31 ( EudraCT Number )
CTR20190416 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: November 4, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
zanubrutinib
BTK inhibitor
bendamustine
rituximab
venetoclax
BGB-3111
Phase 3
Additional relevant MeSH terms:
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Venetoclax
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Bendamustine Hydrochloride
Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors