A Dose-escalating Pilot Study of Orelabrutinib for Newly-diagnosed PCNSL

This is a single arm, single center, open label pilot study of Orelabrutinib combined with Rituximab, high-dose (HD) Methotrexate and Dexamethasone in newly-diagnosed primary central nervous system lymphpoma (PCNSL). The purpose is to evaluate the safety and to find the optimal dose of Orelabrutinib and Methotrexate in this combination treatment for newly-diagnosed PCNSL patients.

Inclusion Criteria: * anti-neoplasm systemic treatement naive primary central nervous system lymphoma * Pathological type is diffuse large B cell lymphoma * Enough residual sample of tumor after pathological diagnosis * ECOG =\3 months * Adequate organ function and adequate bone marrow reserve * Must be able to tolerate lumbar puncture and/or have Omaya tube * Participant or his/her legal agent must be willing to sign a written informed consent document. Exclusion Criteria: * Lymphoma invading outside CNS * Lymphoma only existed in vitreo-retina * Severe or uncontrolled cardiovascular disease * Active hemorrhage within 2 months prior screening * Cerebral ischemic stroke or bleeding within 6 months prior screening * Organ transplantation or allogeneic hematopoietic stem cell transplantation history * Other surgery history within 6 weeks prior screening * Anti-tumor herbal medicine treatment within 4 weeks prior screening * Activated or uncontrolled hepatitis virus B infection (HBsAg positive with/or HBc Ab positive and HBV-DNA titration positive), hepatitis virus C antibody positive, HIV positive. * Uncontrolled active systemic fungal, bacterial, virus or other microbe infection, or intravenous injection of antibiotics needed * Accepted live vaccine or immunization within 4 weeks prior eligibility * Continuously taking drugs with medium / strong inhibition or induction of cytochrome P450 CYP3A is needed * Allergy to orelabrutinib or the subsidiary (or supplementary) material (Hydroxypropyl methylcellulose acetate succinate, mannitol, cross-linked sodium carboxymethylcellulose, hydroxypropyl cellulose, silica and magnesium stearate) * Obvious gastro-bowel disease which may influence the intaking, transportation or absorption of the drug, or total gastrectomy * Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, or drug-related pneumonia, with severe impairment of pulmonary function * Chronic liver damage, severe fatty liver or alcoholic liver disease * Intention to undergo autologous stem cell transplantation * Pregnant or breeding women, or women of childbearing age who are unwilling to take contraceptive measures during the whole study period and within 180 days after the last administration of the study drug; non surgically sterilized men who are unwilling to take contraceptive measures during the whole study period and within 180 days of the last administration of the study drug. * Potentially life-threatening situation, or severe organ dysfunction, or situations the researchers believe not suitable for the trial * Any mental or cognitive impairment which may limit the understanding and implementation of informed consent or the compliance with the study. * previously exposed with WBRT