Safety and Efficacy Study of Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Inclusion Criteria:

• Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Pathologically confirmed de novo DLBCL; subjects must have available archival tissue for central review to be eligible.
• Relapsed or refractory disease, defined as either: 1) recurrence of disease after a complete remission (CR), or 2) partial response (PR), stable disease (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 with suspected residual disease after the treatment regimen directly preceding study enrollment must have biopsy demonstration of residual DLBCL. Subjects who have not received high dose chemotherapy/autologous stem cell transplant (HDT/ASCT) must be ineligible for HDT/ASCT as defined by meeting any of the following criteria: Age ≥ 70 years ,Diffuse lung capacity for carbon monoxide (DLCO) < 50% by pulmonary function test (PFT), Left ventricular ejection fraction (LVEF) < 50% by multiple gated acquisition(MUGA)/echocardiograph (ECHO), Other organ dysfunction or comorbidities precluding the use of HDT/ASCT on the basis of unacceptable risk of treatment-related morbidity, Subject refusal of HDT/ASCT.
• Subjects must have ≥ 1 measurable (> 2 cm in longest dimension) disease sites on computed tomography (CT) scan.

Exclusion Criteria:

• Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue [MALT] lymphoma)
• Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
• Known central nervous system (CNS) lymphoma
• Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 3 weeks of the first dose of study drug
• Radio- or toxin-immunoconjugates within 10 weeks of the first dose of study drug
• Major surgery within 2 weeks of first dose of study drug
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at undue risk
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction

• Any of the following laboratory abnormalities:

  • Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement
  • Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement
  • Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 upper limit of normal (ULN)
  • Creatinine > 2.0 x ULN