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A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL

NCT03336333

Description:

To compare efficacy between zanubrutinib versus bendamustine and rituximab in patients with previously untreated CLL/SLL, as measured by progression free survival.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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
  • SECONDARY ID: 2017-001551-31
  • SECONDARY ID: CTR20190416
  • NCT ID: NCT03336333

Conditions

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
ZanubrutinibBGB-3111Zanubrutinib (patients without del[17p])
BendamustineTreanda, Ribomustin, and LevactB+R
RituximabRituxan, MabTheraB+R
VenetoclaxVenclexta, VenclyxtoZanubrutinib and venetoclax (patients with del[17p])

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Zanubrutinib (patients without del[17p])ExperimentalApproximately 225 subjects in Cohort 1 to receive zanubrutinib
  • Zanubrutinib
B+RExperimentalApproximately 225 subjects in Cohort 1 to receive bendamustine plus rituximab
  • Bendamustine
  • Rituximab
Zanubrutinib patients with del[17p])ExperimentalApproximately 100 subjects in Cohort 2 to receive zanubrutinib
  • Zanubrutinib
Zanubrutinib and venetoclax (patients with del[17p])ExperimentalApproximately 50 subjects in Cohort 3 to receive BGB-3111 and venetoclax
  • Zanubrutinib
  • Venetoclax

Eligibility 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.
      
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 (Zanubrutinib vs. B+R) as determined by independent central review (ICR).
Time Frame:Up to 5 years.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate between treatment groups in Cohort 1
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Overall survival between treatment groups in Cohort 1.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Duration of response between treatment groups in Cohort 1.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Progression-free survival between treatment groups in Cohort 1 determined by investigator assessment (IA).
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Patient-reported outcomes in Cohort 1 measured by the EQ-5D-5L questionnaire.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Overall response rate in Cohort 2.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Progression-free survival in Cohort 2 as determined by ICR.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Duration of response in Cohort 2 as determined by ICR.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Overall response rate in Cohort 3.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Progression-free survival in Cohort 3 as determined by ICR.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Duration of response in Cohort 3 as determined by ICR.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Rate of undetectable minimal residual disease in Cohort 3.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Descriptive statistics will be used to summarize rate of adverse events.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Plasma zanubrutinib concentrations will be summarized by scheduled time of collection.
Time Frame:Up to 5 years.
Safety Issue:
Description:
Measure:Patient-reported outcomes in Cohort 1 measured by the EORTC QLQ-C30 questionnaire.
Time Frame:Up to 5 years.
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

Trial Keywords

  • zanubrutinib
  • BTK inhibitor
  • bendamustine
  • rituximab
  • venetoclax
  • BGB-3111
  • Phase 3

Last Updated

December 13, 2019