The study will include 30 elderly patients age 60-85 with primary CNS DLBCL . Induction treatment will include Rituximab and high dose methotrexate protocol (containing at least methotrexate and one more chemotherapy agent).

Patients with MRI documented response CR or PR will enter the study protocol maintenance phase which will include continous treatment with Ibrutinib 560 mg day until relapse or disease progression or occurrence of limiting toxicities

30 elderly patients age 60-85 with primary CNS DLBCL who will achieve response CR or PR will enter the study protocol maintenance phase.

Induction treatment will include Rituximab and high dose methotrexate protocol (containing at least methotrexate and one more chemotherapy agent).

Patients with MRI documented response CR or PR will enter the study protocol maintenance phase.

Maintenance: 28 day cycles of Ibrutinib 560 mg orally once daily until relapse or disease progression or occurrence of limiting toxicities

Evaluation of response:

Radiologic evaluation by MRI will be performed every 3 months. Neurologic status evaluation every 2 months Neurocognitive evaluation every 6 months

Inclusion Criteria:

• Newly diagnosed PCNSL patients whose age is >60 years and achieved response (CR/PR) after first line immunochemotherapy treatment
• Tissue diagnosis is mandatory unless positive cerebrospinal fluid (CSF) cytology or vitrectomy are diagnostic with no evidence for systemic disease
• No contraindication for high dose methotrexate (HD-MTX) (adequate renal function)
• KPS > 40%, ECOG < 3
• Hematology values must be within the following limits:

Absolute neutrophil count (ANC) ≥ 1000/µl independent of growth factor support Platelets ≥100,000/µl or ≥50,000/µl if bone marrow involvement independent of transfusion support in either situation • Biochemical values within the following limits: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault≥ 40 mL/min

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Exclusion Criteria:

• Major surgery within 4 weeks of randomization.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
• Requires treatment with strong CYP3A inhibitors.
• 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.
• Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
• Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
• 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.