A Study of Ibrutinib With Rituximab in People With Untreated Marginal Zone Lymphoma

Exclusion Criteria

• •Medically apparent central nervous system lymphoma or leptomeningeal disease
• •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible
• •History of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years
• •Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to first dose of ibrutinib/placebo or subject who requires continuous treatment with a strong CYP3A inhibitor
• •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of \>20 mg/day of prednisone) within 28 days of the first dose of study drug
• •Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmias or Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification; or a history of unstable angina, acute coronary syndrome, or myocardial infarction within 6 months of prior to screening
• •Recent infection requiring systemic anti-infective treatment that was completed ≤14 days before the first dose of study drug
• •Any uncontrolled active systemic infection
• •Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
• •Hepatitis B (HBV): All subjects must be screened for hepatitis B and C. Subjects with a positive polymerase chain reaction for hepatitis B must be on entecavir or equivalent therapy as per institutional standard of care. (Hep C patients may be enrolled if other parameters precluding hepatic impairment are met. And they are not undergoing active therapy for hepatitis C
• •Human immunodeficiency virus (HIV): NOTE: HIV is a contraindication if the subject has an active opportunistic infection (OI) within 12 months and CD4 count is below the normal range
• •Any of the following abnormalities:
• •* Absolute neutrophil count (ANC) \<750 cells/mm3 (0.75 x 10\^9/L) unless there is documented bone marrow involvement
• •* Platelet count \<50,000 cells/mm\^3 (50 x 10\^9/L) independent of transfusion support unless there is documented bone marrow involvement
• •* Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≥3.0 x upper limit of normal (ULN)
• •* Creatinine \>2.0 x ULN or Estimated Glomerular Filtration Rate GFR \[Cockcroft-Gault\]) \<30 mL/min
• •* Hemoglobin \<8.0 g/dL unless secondary to hemolysis or documented bone marrow involvement
• •* Bilirubin \>1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• •* PT/INR \>1.5 x ULN and PTT (aPTT) \>1.5 x ULN unless factor XI deficiency or lupus anticoagulant.
• •Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction
• •Major surgery within 4 weeks prior to the first dose of study drug
• •Any life-threatening illness, medical condition, including uncontrolled diabetes mellitus (DM), or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk
• •Lactating or pregnant
• •Unwilling or unable to participate in all required study evaluations and procedures
• •Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
• •Subjects with chronic liver disease with hepatic impairment Child-Pugh class B or C