Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

1. Men and women ≥ 18 years of age. 2. ECOG performance status ≤ 2. 3. Pathologically confirmed de novo DLBCL 4. Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method. 5. Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT 6. Treatment Group 1: Subjects must have ≥ 1 measurable (\> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (\> 1.5 cm in longest dimension) disease sites on CT scan.

1. Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT). 2. Primary mediastinal (thymic) large B-cell lymphoma. 3. Known central nervous system lymphoma. In addition, for subjects in Treatment Group 2, known leptomeningeal involvement is exclusionary. 4. Certain exclusions on prior therapy 5. Major surgery within 2 weeks of first dose of study drug. 6. Any of the following laboratory abnormalities: 1. ANC \< 0.75 x 10\^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests. 2. Platelet count \< 50 x 10\^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests. 3. AST or ALT ≥ 3.0 x upper limit of normal (ULN) 4. Creatinine \> 2.0 x ULN 5. Treatment Group 2 only: Hemoglobin \< 8.0 g/dL 6. Treatment Group 2 only: Total Bilirubin \> 1.5 x ULN 7. Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon) 8. Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor 9. Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.