BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies

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.