Bruton's Tyrosine Kinase Inhibitor Ibrutinib as Maintenance Treatment in Elderly Patients With Primary CNS Lymphoma

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 orvitrectomy 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 ineither situation • Biochemical values within the following limits: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) Totalbilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepaticorigin Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault≥ 40 mL/min

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 symptomaticarrhythmias, congestive heart failure, or myocardial infarction within 6 months ofScreening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined bythe 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 oractive Hepatitis B Virus infection or any uncontrolled active systemic infectionrequiring intravenous (IV) antibiotics.
• Any life-threatening illness, medical condition, or organ system dysfunction which, inthe investigator's opinion, could compromise the subject's safety, interfere with theabsorption or metabolism of ibrutinib capsules, or put the study outcomes at unduerisk.