Ibrutinib in Patients With Refractory/Relapsed Non-GCB Diffuse Large B-cell Lymphoma Non-candidates to ASCT

Inclusion Criteria: 1. Subjects with confirmed histologically diagnosis of diffuse large B-cell lymphoma. 2. Subjects must be 18 years of age or older. 3. Non-germinal center B-cell-like (GCB) subtype according to Hans algorithm (local laboratories). -A central review will be performed for confirmation of the germinal center B-cell-like, however even when negative results are reported, the patient will still be part of the study if clinical benefit after cycle 4 is documented (stable disease, partial response and complete response). 4. Relapsed or refractory disease after: * at least 1 prior line of therapy that includes rituximab in combination with chemotherapy, or, * after previous ASCT, or, * after reduced intensity conditioning allogeneic transplant, unless patient is receiving immunosuppressive drugs or active graft versus host disease is present at study entry. 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 6. Baseline FDG-PET scan demonstrating positive lesions (Deauville 4 or 5) compatible with CT defined anatomical tumor sites. 7. Hematology values must be within the following limits: 1. absolute neutrophil count (ANC) ≥1000/μL independent of growth factor support. 2. platelets ≥100000/μL or ≥50000/μL if bone marrow involvement independent of transfusion support in either situation. 8. Biochemical values within the following limits: 1. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN). 2. total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin. 3. serum creatinine ≤2 x ULN or estimated creatinine clearance (CCr) ≥30 mL/min. 9. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug. 10. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. 11. Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing and able to participate in the study. Exclusion Criteria: 1. Prior malignancy other than DLBCL, with the exception of adequately treated basal cell or squamous cell skin tumor, in situ cervical cancer, or other tumor from which the patient has been disease free for at least 2 years or which will not limit survival to \< 2 years (Note: these cases must be discussed with the Principal Investigator). 2. Candidates to autologous stem cell transplant. \- Young patients with more than a previous line and refractory could be considered as not suitable for autologous stem cell transplant and, therefore, are eligible for this study. 3. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety,interfere with the absorption or metabolism of ibrutinib, or put the study outcomes at undue risk. 4. 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. 5. 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. 6. Treatment with any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 3 weeks before first dose of study drug. 7. Prior treatment with ibrutinib or other BTK inhibitors. 8. Central nervous system (CNS) involvement by lymphoma. 9. History of stroke or intracranial hemorrhage within 6 months prior to randomization. 10. Requires anticoagulation with warfarin or equivalent Vitamin K antagonists. 11. Requires treatment with strong CYP3A inhibitors. 12. Grade ≥2 toxicity (other than alopecia) related to prior anticancer therapy including radiation. 13. Known history of human immunodeficiency virus (HIV), active hepatitis C virus (HCV) (HCV; RNA polymerase chain reaction \[PCR\]-positive) or active Hepatitis B virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection requiring IV antibiotics. Subjects with PCR-negative HBV are permitted in the study. 14. Major surgery within 4 weeks before first dose of study drug. 15. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 16. Pregnancy or lactation