Ibrutinib + R-CHOP Followed by Ibrutinib Maintenance

INCLUSION CRITERIA * Histologically confirmed DLBCL not otherwise specified (NOS). Patients with follicular lymphoma IIIB and large B-cell lymphoma with IRF4 rearrangement can be also included. * ABC type defined by Lymph2Cx on the NanoString platform. Note: A formalin fixed paraffin embedded lymph node or tumor biopsy specimen must be submitted to Central Pathology for review during the Screening Period. The specimen must have been acquired by a surgical incision or excision biopsy or from a core needle biopsy * Previously untreated disease * Age ≥ 18 and \< 65 years * IPI score ≥ 2 * Ann Arbor stage II-IV disease * Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions * Normal blood count as defined as: absolute neutrophil count ≥1.0 × 10 9 /L independent of growth factor support, platelet count ≥ 100,000/mm 3 or ≥ 50,000/mm 3 if bone marrow (BM) involvement independent of transfusion support in either situation Normal organ functions defined as: creatinine ≤2 times the upper limit of normal (ULN) or estimated Glomerular Filtration Rate (Cockroft-Gault) ≥40 ml/min/1.73m 2 , aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× the ULN; total bilirubin ≤ 1.5 × the ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN; International normalized ratio (INR) \< 1.5 × the ULN in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) \< 1.5 × the ULN in the absence of a lupus anticoagulant * Patients with occult or prior hepatitis B infection (defined as HBsAg negative, anti-HBs positive and /or anti-HBc positive) may be included if hepatitis B virus (HBV) DNA is undetectable. These patients must be willing to undergo bi-monthly DNA testing and they should receive prophylaxis with Lamivudine * No active hepatitis C virus (HCV) infection * Known availability of biopsy material * No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma) * Absence of active infections * No peripheral neuropathy or active neurological non-neoplastic disease of CNS * No major surgical intervention prior 3 months to enrolment if not due to lymphoma and/or no other disease life-threatening that can compromise chemotherapy treatment * Patient with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study. * No previous malignancies or patient with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study or patients with any other malignancy in remission without treatment for at least 5 years prior to enrolment * 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. - Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[Beta-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. * Life expectancy \> 6 months * Written informed consent from the patient stating understanding of the purpose and procedures required by the study and willingness to take part in the study EXCLUSION CRITERIA * DLBCL including High grade B-cell Lymphomas, both with double hit and NOS according to the 2017 Revised WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues * GCB-DLBCL after centralized COO profiling * Any other histologies than DLBCL: composite or transformed disease. * Primary mediastinal lymphoma (PMBL) * Known central nervous system lymphoma * Primary testicular lymphoma * Any prior lymphoma therapy * Contraindication to any drug in the chemotherapy regimen * Left ventricular ejection fraction (LVEF) \< 50% * Neuropathy ≥ grade 2 * Seropositive for or active viral infection with HBV * HBsAg positive * HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable viral DNA * Known seropositive active HCV * Human immunodeficiency virus (HIV) infection * Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma): creatinine ≥ 2 times the ULN (unless creatinine clearance normal, or calculated creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula); AST or ALT ≥3 × the ULN; total bilirubin \>1.5 × the ULN: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN; INR \> 1.5 × the ULN in the absence of therapeutic anticoagulation; PTT or aPTT \> 1.5 × the ULN in the absence of a lupus anticoagulant" * History of stroke or intracranial hemorrhage within the past 6 months. * Requires anticoagulation with warfarin or equivalent vitamin K antagonists * Requires treatment with strong CYP3A inhibitors * History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances * 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 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. * Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics * Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment * Prior malignancies other than lymphoma in the last 5 years with exception of currently treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix * Any other medical or psychological condition that might preclude participation in the study or impair the patient's ability to give informed consent. * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk. * If female, the patient is pregnant or breast-feeding