BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies
Condition: B-cell Lymphoid Malignancies
MeSH terms: Neoplasms
Intervention: Zanubrutinib; Obinutuzumab
Intervention MeSH terms: Obinutuzumab; Zanubrutinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 119.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BGB-3111; Zanubrutinib; Obinutuzumab; Lymphoma; Leukemia; Therapeutic uses; B-cell

Summary:

      This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in
      combination with obinutuzumab in participants with B-cell lymphoid malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged ≥18 years, able and willing to provide written informed consent and to comply
             with the study protocol.

          -  Laboratory parameters as specified below:

               -  Hematologic: Platelet count >40x10^9/liter (L) (may be post-transfusion);
                  absolute neutrophil count >1.0x10^9/L (growth factor use is allowed to bring
                  pre-treatment neutrophils to >1.0x10^9 cells/L if marrow infiltration is
                  involved).

               -  Hepatic: Total bilirubin <3 x upper limit normal (ULN); and aspartate
                  aminotransferase and alanine transaminase ≤3 x ULN.

               -  Renal: Creatinine clearance ≥50 milliliters/minute (as estimated by the Cockcroft
                  Gault equation or as measured by nuclear medicine scan or 24-hour urine
                  collection); participants requiring hemodialysis will be excluded.

          -  Anticipated survival of at least 6 months.

          -  Eastern Cooperative Oncology Group performance status of 0 to 2.

          -  Female participants of childbearing potential and non-sterile males must have agreed
             to practice at least one of the following methods of birth control with partner(s)
             throughout the study and for ≥3 months after discontinuing zanubrutinib or ≥18 months
             following obinutuzumab treatment, whichever was longer: total abstinence from sexual
             intercourse, double barrier contraception, intra uterine device or hormonal
             contraceptive initiated at least 3 months prior to first administration of study drug.

          -  Male participants must have not donated sperm from first study drug administration,
             until 3 months after zanubrutinib discontinuation or 18 months following obinutuzumab
             treatment, whichever is longer.

        Exclusion Criteria:

          -  Known central nervous system lymphoma or leukemia.

          -  Known prolymphocytic leukemia or history of, or currently suspected, Richter's
             syndrome.

          -  Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.

          -  History of significant cardiovascular disease.

          -  Severe or debilitating pulmonary disease.

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.

          -  Prior Bruton tyrosine kinase inhibitor treatment.

          -  Used medications which were strong cytochrome P450 (CYP) 3A inhibitors and strong
             CYP3A inducers.

          -  Vaccination with a live vaccine within 28 days of the initiation of treatment.

          -  Allogeneic stem cell transplantation within 6 months, or had active graft versus host
             disease requiring ongoing immunosuppression.

          -  Receipt of the following treatment prior to first administration of zanubrutinib,
             corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or
             radiotherapy within 3 weeks, monoclonal antibody within 4 weeks.

          -  Participated in any investigational drug study within 28 days of study entry, or not
             recovered from non-hematologic toxicity of any prior chemotherapy up to ≤ Grade 1
             (except for alopecia).

          -  History of other active malignancies within 2 years of study entry.

          -  Major surgery in the past 4 weeks.

          -  Active symptomatic fungal, bacterial and/or viral infection including evidence of
             infection with human immunodeficiency virus, human T cell lymphotropic virus
             seropositive status.

          -  Inability to comply with the study procedures.

          -  Pregnant or nursing women.

          -  Any illness or condition that in the opinion of the investigator may have affected the
             safety of treatment or evaluation of any study's endpoints.