A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma
Condition: B-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Intervention: Zanubrutinib
Intervention description: Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.
Intervention MeSH terms: Zanubrutinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This phase I clinical study was to investigate the safety, tolerability, and
      pharmacokinetics/pharmacodynamics of Bruton tyrosine kinase (BTK) inhibitor zanubrutinib
      (BGB-3111) in Chinese participants with B-cell lymphoma by conducting in two stages, the
      first stage being the safety assessment of dose and the second stage being the dose
      expansion.

      Part I: Safety evaluation - according to the results of preclinical toxicological trials and
      the results of the phase I clinical study conducted in Australia and New Zealand, two
      regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily [BID]), administered
      in the morning and at night, or 320 mg once daily [QD]) and "3+3" design was adopted for the
      assessment. The recommended dose and method of administration of the phase II clinical study
      was determined according to the Part I results.

      Part II: Dose expansion - this stage was to further evaluate the preliminary anti-tumor
      effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal
      zone lymphoma (MZL), approximately 20 participants with relapsed or refractory FL or MZL were
      to be enrolled. The recommended Phase 2 dose (RP2D) was used in Part II.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Men and women between the age of 18-75 years.

          -  Participants with B-cell lymphoma (defined by World Health Organization
             classification) refractory or relapsed following at least one line of therapy.

          -  Judged by the investigator as requiring treatment.

          -  Eastern Cooperative Oncology Group performance status of 0-1.

          -  Life expectancy of at least 4 months.

          -  Adequate hematological function.

          -  Adequate renal function.

          -  Adequate liver function.

          -  Adequate coagulation function.

          -  Female participants of childbearing potential and non-sterile males must have
             practiced at least one of the following methods of birth control with partner(s)
             throughout the study and for 90 days after discontinuing study drug: total abstinence
             from sexual intercourse, double-barrier contraception, intrauterine device or hormonal
             contraceptive initiated at least 3 months prior to first dose of study drug.

          -  Male participants must not have donated sperm from start of study drug administration,
             until 90 days after discontinuation of treatment.

        Key Exclusion Criteria:

          -  With central nervous system involvement of the disease.

          -  The pathological type of the disease had disease transformation.

          -  Had underdone allogeneic hematopoietic stem cell transplantation.

          -  Had received corticosteroid anti-neoplastic treatment within 7 days before the first
             dose, has received radiotherapy and chemotherapy within 4 weeks before the first dose
             or has received treatment with monoclonal antibody within 4 weeks before the first
             dose.

          -  Had received BTK inhibitor treatment prior to enrollment.

          -  Had received chemotherapy and has not yet recovered from toxicity

          -  Had received Chinese herbal medicine as anti-neoplastic therapy within 4 weeks before
             starting study treatment.

          -  History of other malignancies within 2 years before study.

          -  With uncontrolled systemic infection.

          -  Major surgery in the past 4 weeks.

          -  With known HIV, or active hepatitis B or hepatitis C virus infection.

          -  With cardiovascular disease of New York Heart Association Classification ≥ 3.

          -  Significant electrocardiogram abnormalities.

          -  Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease
             that in the investigator's opinion would adversely impact on his/her participation in
             the study.

          -  Inability to comply with study procedures.

          -  Was currently taking anticoagulant drugs.

          -  Was currently taking potent cytochrome P450 3A inhibitor or inducer.

          -  Had stroke or cerebral hemorrhage within 6 months before enrollment.

        Note: Other protocol defined Inclusion/Exclusion criteria may have applied.