This is a prospective single arm, phase II clinical trial to observe the efficacy and safety of orelabrutinib combined with pemetrexed in the treatment for patients with relapsed/refractory central nervous system lymphoma.

Inclusion Criteria:

1. Age between 18 to 75 years old (including 18 and 75)
2. Diagnosed as diffuse large B-cell lymphoma; Recurrence or progression of central nervous system disease confirmed by imaging ± tissue biopsy pathology or cerebrospinal fluid flow cytometry; Secondary central nervous system lymphoma can also be admitted when the systemic disease is well controlled
3. Having at least one measurable lesions
4. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 ( ECOG 3 due to tumors can be included after being fully assessed by the investigator)
5. Life expectancy no less than 1 month
6. enough main organ function
7. Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study
8. Agreeing to sign the written informed consents

Exclusion Criteria:

1. Poor peripheral disease control of secondary central nervous system lymphoma
2. Patients used pemetrexed or orelabrutinib in the past
3. Active malignant tumor need be treated at the same time
4. Other malignant tumor history
5. Serious surgery and trauma less than two weeks
6. Patients with active tuberculosis
7. Systemic therapy for serious acute/chronic infection
8. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
9. HIV-positive, AIDS patients and untreated active hepatitis
10. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
11. Patients with a history of mental illness or drug abuse
12. Poor compliance during the trial and/or follow-up phase
13. Allergies or people who are known to be allergic to any active ingredients, excipients, mouse-derived products or heterologous protein contained in this trial
14. Researchers determine unsuited to participate in this trial