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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

Tracking Information
First Submitted Date  ICMJE November 1, 2017
First Posted Date  ICMJE November 8, 2017
Last Update Posted Date November 4, 2019
Actual Study Start Date  ICMJE November 2, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2019)
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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
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. ]
Change History Complete list of historical versions of study NCT03336333 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2019)
  • Overall response rate between treatment groups in Cohort 1 [ Time Frame: Up to 5 years. ]
  • Overall survival between treatment groups in Cohort 1. [ Time Frame: Up to 5 years. ]
  • Duration of response between treatment groups in Cohort 1. [ Time Frame: Up to 5 years. ]
  • Progression-free survival between treatment groups in Cohort 1 determined by investigator assessment (IA). [ Time Frame: Up to 5 years. ]
  • Patient-reported outcomes in Cohort 1 measured by the EQ-5D-5L questionnaire. [ Time Frame: Up to 5 years. ]
  • Overall response rate in Cohort 2. [ Time Frame: Up to 5 years. ]
  • Progression-free survival in Cohort 2 as determined by ICR. [ Time Frame: Up to 5 years. ]
  • Duration of response in Cohort 2 as determined by ICR. [ Time Frame: Up to 5 years. ]
  • Overall response rate in Cohort 3. [ Time Frame: Up to 5 years. ]
  • Progression-free survival in Cohort 3 as determined by ICR. [ Time Frame: Up to 5 years. ]
  • Duration of response in Cohort 3 as determined by ICR. [ Time Frame: Up to 5 years. ]
  • Rate of undetectable minimal residual disease in Cohort 3. [ Time Frame: Up to 5 years. ]
  • Descriptive statistics will be used to summarize rate of adverse events. [ Time Frame: Up to 5 years. ]
  • Plasma zanubrutinib concentrations will be summarized by scheduled time of collection. [ Time Frame: Up to 5 years. ]
  • Patient-reported outcomes in Cohort 1 measured by the EORTC QLQ-C30 questionnaire. [ Time Frame: Up to 5 years. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2017)
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing BGB-3111 With Bendamustine Plus Rituximab in Patients With Previously Untreated CLL or SLL
Official Title  ICMJE 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)
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Intervention  ICMJE
  • 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: 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
  • Drug: Venetoclax
    Venetoclax will be administered by mouth once daily.
    Other Name: Venclexta, Venclyxto
Study Arms  ICMJE
  • Experimental: Zanubrutinib (patients without del[17p])
    Approximately 225 subjects in Cohort 1 to receive zanubrutinib
    Intervention: Drug: Zanubrutinib
  • Experimental: B+R
    Approximately 225 subjects in Cohort 1 to receive bendamustine plus rituximab
    Interventions:
    • Drug: Bendamustine
    • Drug: Rituximab
  • Experimental: Zanubrutinib patients with del[17p])
    Approximately 100 subjects in Cohort 2 to receive zanubrutinib
    Intervention: Drug: Zanubrutinib
  • Experimental: Zanubrutinib and venetoclax (patients with del[17p])
    Approximately 50 subjects in Cohort 3 to receive BGB-3111 and venetoclax
    Interventions:
    • Drug: Zanubrutinib
    • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 16, 2019)
600
Original Estimated Enrollment  ICMJE
 (submitted: November 7, 2017)
467
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: BeiGene +1-877-828-5568 clinicaltrials@beigene.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Czechia,   France,   Italy,   New Zealand,   Poland,   Russian Federation,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03336333
Other Study ID Numbers  ICMJE BGB-3111-304
2017-001551-31 ( EudraCT Number )
CTR20190416 ( Registry Identifier: Center for drug evaluation, CFDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jason Paik, MD BeiGene
PRS Account BeiGene
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP